Clinical trial NCT05206604
Conditions: Healthy
Sponsor: Pfizer
Start date: 2022-02-09; Completion date: 2022-08-12
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of the study is to evaluate the safety, (local and systemic) tolerability, and pharmacokinetics following multiple doses of topically applied, maximum feasible formulations of PF-07295324 (0.12% w/w) or PF-07259955 (2% w/w), on approximately 20% body surface area (BSA), in healthy adult participants.

Detailed description:

Arms: arm 1: Ointment arm 2: Cream
Interventions: intervention 1: PF-07295324 intervention 2: PF-07259955
Intervention descriptions: intervention 1: Ointment intervention 2: Cream

Protocol documents:
Prot_000.pdf: 
PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 1 
 
 
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. 
 
 
 
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, VEHICLE- 
CONTROLLED, FIRST-IN-HUMAN, MULTIPLE-DOSE STUDY, TO 
INVESTIGATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS, OF 
TOPICALLY ADMINISTERED PF-07295324 AND PF-07259955, IN HEALTHY 
ADULT PARTICIPANTS 
Study Intervention Number: 
[PF-07295324] [PF-07259955] 
Study Intervention Name: 
N/A 
US IND Number: 
 
EudraCT Number: 
N/A 
ClinicalTrials.gov ID: 
N/A 
Protocol Number: 
C4711001 
Phase: 
Phase 1 
Brief Title: A Phase 1, FIH Study of Multiple Doses of Topically Administered PF- 
07295324 and PF-07259955, in Healthy Participants. 
 
 
CCI 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 2 
 
 
Document History 
 
Document 
Version Date 
Amendment 1 
21 April 2022 
Original protocol 
06 December 2021 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any global protocol administrative 
change letter(s). 
 
Protocol Amendment Summary of Changes Table 
Amendment 1 (21-April-2022) 
Overall Rationale for the Amendment: Update the optional cohorts (cohorts 3 and 4) to 
clarify and allow these cohorts to repeat doses studied in previous cohorts. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4.1 Overall Design; 
Section 4.3 Justification for 
Dose; Section 1.1 Synopsis, 
Section 1.2 Schema and 
Section 1.3 SoA 
Added language to allow 
to repeat doses studied in 
Cohort 1 and Cohort 2 in 
optional cohorts (ie, 
Cohort 3 and Cohort 4). 
To clarify that doses tested 
in previous cohorts may be 
repeated to understand 
and/or further evaluate the 
safety/tolerability/PK 
observed in previous 
cohorts if the stopping 
criteriaare not met. 
Section 4.1 Overall Design, 
Section 4.3 Justification for 
Dose, Section 1.2 Schema 
and Section 1.3 SoA, Section 
6.5 Dose Modification 
Added language to allow 
study of either PF- 
07295324 or PF- 
07259955 in Cohort 4 
after review of data from 
Cohorts 1-3. 
Cohort 4 may be used to 
further investigate PF- 
07295324 or PF-07259955 
safety, tolerability and/or 
PK after review of Cohorts 
1, 2 and 3. 
Section 6.1.1.2 Calculation 
of Per Application Dose and 
throughout document (where 
applicable) 
To clarify that that BSA 
administered in this study 
is less than or equal to 
4000 cm2. 
In this study, the BSA 
administered is up to 20% 
or 4000 cm2. 
Section 1.1 Synopsis, 
Section 1.3 SoA, Section 4.1 
Overall Design, Section 
10.1.8 Source Documents, 
Section 10.1.11 Sponsor’s 
Qualified Medical Personnel, 
Section 10.4.1 Male 
Revisions outlined in the 
PACL dated 26 Jan 2022 
have been incorporated. 
Minor revisions were made 
to reconcile follow up 
contact/EOS to D41±3 days, 
to clarify the restriction on 
donating sperm would be 90 
days, and since this is a 
PCRU study, wordings in 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 3 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Participant Reproductive 
Inclusion Criteria 
Sections 10.1.8 and 10.1.11 
were updated accordingly. 
Section 10.9 Abbreviations 
Added CTMS, PACL, 
PCRU and removed 
STOD. 
Revised per changes 
specified in the protocol 
amendment. 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 4 
 
 
TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................... 10 
LIST OF FIGURES .................................................................................................................. 10 
1. PROTOCOL SUMMARY ................................................................................................... 11 
1.1. Synopsis ................................................................................................................... 11 
1.2. Schema..................................................................................................................... 14 
1.3. Schedule of Activities .............................................................................................. 15 
1.3.1. Schedule of Activities from Screening to End of Study (EOS): 
Multiple doses of topical application for 10 days ............................................. 15 
1.3.2. Vitals, ECGs, PK, and PD Sampling Schedule on D1 and D10 .................. 18 
2. INTRODUCTION ................................................................................................................ 19 
2.1. Study Rationale ........................................................................................................ 19 
2.2. Background .............................................................................................................. 19 
2.2.1. Nonclinical Pharmacology .......................................................................... 20 
2.2.1.1. Nonclinical Pharmacology for PF-07295324 ............................ 20 
2.2.1.2. Nonclinical Pharmacology for PF-07259955 ............................ 21 
2.2.2. Nonclinical Pharmacokinetics and Metabolism .......................................... 21 
2.2.2.1. Brief Summary for PF-07295324 ............................................. 21 
2.2.2.2. Brief Summary for PF-07259955 .............................................. 22 
2.2.3. Nonclinical Safety ....................................................................................... 23 
2.2.3.1. Nonclinical Safety for PF-07295324 ......................................... 23 
2.2.3.2. Nonclinical Safety for PF-07259955 ......................................... 24 
2.2.4. Clinical Overview ....................................................................................... 24 
2.3. Benefit/Risk Assessment ......................................................................................... 24 
2.3.1. Risk Assessment ......................................................................................... 26 
2.3.2. Benefit Assessment ..................................................................................... 27 
2.3.3. Overall Benefit/Risk Conclusion ................................................................ 27 
3. OBJECTIVES AND ENDPOINTS ..................................................................................... 27 
4. STUDY DESIGN ................................................................................................................. 28 
4.1. Overall Design ......................................................................................................... 28 
4.2. Scientific Rationale for Study Design ..................................................................... 29 
4.2.1. Diversity of Study Population ..................................................................... 30 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 5 
 
 
4.2.2. Choice of Contraception/Barrier Requirements .......................................... 30 
4.2.3. Collection of Retained Research Samples ................................................... 30 
4.3. Justification for Dose ............................................................................................... 30 
4.3.1. Dose rationale for PF-07295324 ................................................................. 31 
4.3.2. Dose rationale for PF-07259955 ................................................................. 32 
4.4. End of Study Definition ........................................................................................... 34 
5. STUDY POPULATION ...................................................................................................... 34 
5.1. Inclusion Criteria ..................................................................................................... 34 
5.2. Exclusion Criteria .................................................................................................... 35 
5.3. Lifestyle Considerations .......................................................................................... 38 
5.3.1. Meals and Dietary Restrictions ................................................................... 38 
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................. 38 
5.3.3. Activity ....................................................................................................... 39 
5.3.4. Contraception .............................................................................................. 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 ............................................................................................. 40 
6.1.1.1. PF-07295324 and PF-07259955 Administration ....................... 40 
6.1.1.2. Calculation of Per Application Dose .......................................... 41 
6.1.1.3. Application of Investigational Product ...................................... 41 
6.2. Preparation, Handling, Storage, and Accountability ............................................... 42 
6.2.1. Preparation and Dispensing ......................................................................... 43 
6.3. Measures to Minimize Bias: Randomization and Blinding ..................................... 43 
6.3.1. Allocation to Study Intervention ................................................................. 43 
6.3.2. Breaking the Blind ...................................................................................... 43 
6.4. Study Intervention Compliance ............................................................................... 44 
6.5. Dose Modification ................................................................................................... 44 
6.5.1. Dose Stopping Rules ................................................................................... 44 
6.5.2. Individual Stopping Rules ........................................................................... 46 
6.6. Continued Access to Study Intervention After the End of the Study ...................... 46 


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Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
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6.7. Treatment of Overdose ............................................................................................46 
6.8. Concomitant Therapy ............................................................................................. 47 
6.8.1. Rescue Medicine ........................................................................................ 47 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................... 47 
7.1. Discontinuation of Study Intervention .................................................................... 47 
7.1.1. ECG Changes ............................................................................................. 48 
7.1.2. Potential Cases of Acute Kidney Injury ..................................................... 48 
7.2. Participant Discontinuation/Withdrawal From the Study ...................................... 49 
7.2.1. Withdrawal of Consent .............................................................................. 50 
7.3. Lost to Follow up .................................................................................................... 50 
8. STUDY ASSESSMENTS AND PROCEDURES .............................................................. 51 
8.1. Efficacy Assessments ............................................................................................. 52 
8.2. Safety Assessments ................................................................................................. 52 
8.2.1. Physical Examinations ............................................................................... 52 
8.2.2. Vital Signs .................................................................................................. 53 
8.2.3. Electrocardiograms ..................................................................................... 53 
8.2.4. Clinical Safety Laboratory Assessments .................................................... 54 
8.2.5. Application Site Assessments .................................................................... 54 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting ................. 56 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information ...... 56 
8.3.1.1. Reporting SAEs to Pfizer Safety .............................................. 57 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF .................. 57 
8.3.2. Method of Detecting AEs and SAEs .......................................................... 57 
8.3.3. Follow-Up of AEs and SAEs ..................................................................... 57 
8.3.4. Regulatory Reporting Requirements for SAEs .......................................... 58 
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure .................................................... 58 
8.3.5.1. Exposure During Pregnancy ..................................................... 58 
8.3.5.2. Exposure During Breastfeeding ................................................ 60 
8.3.5.3. Occupational Exposure ............................................................. 60 
8.3.6. Cardiovascular and Death Events ............................................................... 61 


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Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
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8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs ............................................................................. 61 
8.3.8. Adverse Events of Special Interest ............................................................. 61 
8.3.8.1. Lack of Efficacy ....................................................................... 61 
8.3.9. Medical Device Deficiencies ..................................................................... 61 
8.3.10. Medication Errors ..................................................................................... 61 
8.4. Pharmacokinetics .................................................................................................... 62 
8.4.1. Pharmacokinetics of PF-07295324 ............................................................ 63 
8.4.2. Pharmacokinetics for PF-07259955 ........................................................... 63 
8.5. Genetics .................................................................................................................. 63 
8.5.1. Specified Genetics ...................................................................................... 63 
8.5.2. Retained Research Samples for Genetics ................................................... 63 
CCI 
 
8.7. Immunogenicity Assessments ................................................................................ 65 
8.8. Health Economics ................................................................................................... 65 
9. STATISTICAL CONSIDERATIONS ................................................................................ 65 
9.1. Statistical Hypotheses ............................................................................................. 65 
9.2. Analysis Sets ........................................................................................................... 65 
9.3. Statistical Analyses ................................................................................................. 66 
9.3.1. Efficacy Analyses ...................................................................................... 66 
9.3.2. Safety Analyses .......................................................................................... 66 
9.3.2.1. Electrocardiogram Analyses ..................................................... 66 
9.3.3. Pharmacokinetic Analyses ......................................................................... 67 
9.3.3.1. Derivation of Pharmacokinetic Parameters .............................. 67 
9.3.3.2. Statistical Methods for PK Data ............................................... 68 
CCI 
 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 8 
 
 
9.4. Interim Analyses ..................................................................................................... 69 
9.5. Sample Size Determination .................................................................................... 69 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.......................................................................................................... 70 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............... 70 
10.1.1. Regulatory and Ethical Considerations .................................................... 70 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP ........................................................................ 70 
10.1.2. Financial Disclosure ................................................................................. 71 
10.1.3. Informed Consent Process ....................................................................... 71 
10.1.4. Data Protection ......................................................................................... 72 
10.1.5. Committees Structure ............................................................................... 72 
10.1.5.1. Data Monitoring Committee ................................................... 72 
10.1.6. Dissemination of Clinical Study Data ...................................................... 72 
10.1.7. Data Quality Assurance ............................................................................ 73 
10.1.8. Source Documents ................................................................................... 74 
10.1.9. Study and Site Start and Closure .............................................................. 75 
10.1.10. Publication Policy .................................................................................. 76 
10.1.11. Sponsor’s Qualified Medical Personnel ................................................. 76 
10.2. Appendix 2: Clinical Laboratory Tests ................................................................ 78 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ..................................................................... 79 
10.3.1. Definition of AE ....................................................................................... 79 
10.3.2. Definition of an SAE ................................................................................ 80 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period ........................................................................... 81 
10.3.4. Reporting of SAEs ................................................................................... 85 
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................ 86 
10.4.1. Male Participant Reproductive Inclusion Criteria ....................................86 
10.4.2. Female Participant Reproductive Inclusion Criteria ................................ 86 
10.4.3. Contraception Methods ............................................................................ 86 
10.5. Appendix 5: Genetics ........................................................................................... 88 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments 
and Study Intervention Rechallenge Guidelines ....................................................... 89 
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ................................... 91 
10.8. Appendix 8: Alternative Measures During Public Emergencies ......................... 93 
10.8.1. Eligibility ................................................................................................. 93 
10.8.2. Telehealth Visits ....................................................................................... 93 
10.8.3. Alternative Facilities for Safety Assessments .......................................... 93 
10.8.3.1. Laboratory Testing ................................................................. 93 
10.8.3.2. Imaging ................................................................................... 94 
10.8.3.3. Electrocardiograms ................................................................. 94 
10.8.4. Study Intervention .................................................................................... 94 
10.8.5. Home Health Visits .................................................................................. 94 
10.8.6. Adverse Events and Serious Adverse Events........................................... 94 
10.8.7. Efficacy Assessments ............................................................................... 94 
10.8.8. Independent Oversight Committees ......................................................... 94 
10.9. Appendix 9: Abbreviations ................................................................................... 95 
11. REFERENCES .................................................................................................................. 99 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
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LIST OF TABLES 
Table 1. 
Schedule of Activities from Screening to End of Study .......................... 15 
Table 2. 
Schedule of Activities for Vitals, ECGs,, PK, and PD on Day 1 and 
Day 10 ...................................................................................................... 18 
Table 3. 
Projected steady-state exposures and Safety Margins Following 
Administration of Multiple Topical Doses of PF-07295324 
(0.12%), once daily or twice daily on 10-20% BSA, in Healthy 
Adult Participants ..................................................................................... 31 
Table 4. 
Projected steady-state exposures and Safety Margins Following 
Administration of Multiple Topical Doses of PF-07259955 (2%), 
once daily or twice daily on 10-20% BSA, in Healthy Adult 
Participants ............................................................................................... 33 
Table 5. 
Skin Irritation Assessment Using Draize Scoring .................................... 55 
Table 6. 
Plasma PK Parameters* ........................................................................... 68 
Table 7. 
Protocol Required Safety Laboratory Assessments .................................. 78 
 
 
LIST OF FIGURES 
Figure 1. 
Study Schema ........................................................................................... 14 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 11 
 
 
1. PROTOCOL SUMMARY 
1.1. Synopsis 
Brief Title: A Phase 1, FIH Study of Multiple Doses of Topically Administered PF-07295324 
and PF-07259955, in Healthy Participants. 
 
Rationale: The purpose of the study is to evaluate the safety, (local and systemic) tolerability, 
and pharmacokinetics following multiple doses of topically applied, maximum feasible 
formulation of PF-07295324 (0.12% w/w) or PF-07259955 (2% w/w), on approximately 20% 
BSA in healthy adult participants. 
 
The safety, local and systemic tolerability, and pharmacokinetics from this study will support 
the parallel clinical development of PF-07295324 and PF-07259955. 
 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• 
To evaluate the safety, and local and 
systemic tolerability, of PF-07295324 and 
PF-07259955, following multiple doses 
of topically administered PF-07295324 or 
PF-07259955, on approximately 20% BSA 
in healthy adult participants. 
• 
Incidence and severity of systemic AEs, safety 
laboratory tests, vital signs (including blood 
pressure and pulse rate), and heart rhythms as 
assessed via 12-lead electrocardiogram (ECG). 
• 
Incidence and severity of application site AEs 
as assessed by Draize score. 
Secondary: 
Secondary: 
• 
To characterize plasma PK following 
multiple topical applications of PF-07295324 
and PF-07259955. 
• 
Plasma PK of multiple topical doses of 
PF-07295324 and PF-07259955, as data permits: 
Day 1: Cmax, Tmax, Cavg, Ctrough, AUCtau 
Day 10: Cmax, Tmax, Cavg, Ctrough, AUCtau, Rac 
(Cmax) , Rac(AUCtau), t½, CL/F, and Vz/F 
CCI 
 
 
 
 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
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Overall Design 
Brief Summary 
C4711001 is an investigator- and participant-blinded, interventional, randomized, 
vehicle-controlled, Phase 1 study to evaluate the safety, local and systemic tolerability, and 
pharmacokinetics of maximum feasible formulation of topical JAK inhibitors, PF-07295324 
(0.12%) and PF-07259955 (2%) in healthy adult participants. 
 
In minipigs, topical administration of an equivalent dose of PF-07295324 (0.12%) or PF- 
07259955 (2%), resulted in minimal non-adverse local skin irritation at maximal feasible 
formulation based on 6-week dermal toleration assessment (Section 2.2.3.1 and 
Section 2.2.3.2). 
 
No dose escalation is planned for this study. 
 
Due to similar pharmacology, same trial objectives, common study design elements, and 
identical safety monitoring plan, this FIH study will use a platform trial design. Under this 
platform design, the safety and tolerability of both the JAK inhibitors PF-07295324 and PF- 
07259955 will be investigated in healthy adult participants, under 1 single Phase 1 study 
protocol, C4711001. 
 
Intervention Groups and Duration 
 
This study will enroll healthy adult participants in ≤4 cohorts: 2 planned cohorts (Cohort 1 
and Cohort 2) and 2 optional cohorts (Cohort 3 and Cohort 4) with approximately 6 
participants/cohort, randomized as 4 active:2 vehicle. 
 
In each cohort, participants confirming eligibility, will be admitted to the Clinical Research 
Unit (CRU), on Day -1. Participants enrolled in Cohort 1 and Cohort 2 will receive multiple 
topical applications of assigned study intervention, Q12H, from Day 1 to Day 9, with only 
morning (AM) application on Day 10. Participants will be discharged on Day 12, following 
the completion of all discharge procedures specified in the Schedule of Activities (SoA) of 
the protocol. Participants will be scheduled for a follow-up phone contact, approximately on 
Study Day 41±3 days. 
 
Cohort 1 will be assigned to PF 07295324/vehicle, applied topically, as an ointment. Cohort 
2 will be assigned to PF 07259955/vehicle, applied topically, as a cream. 
 
Based on emerging data from Cohort 1 & Cohort 2, 1 optional cohorts (6 participants/cohort, 
4:2 active:vehicle) for each intervention may be enrolled in this study. Optional Cohort 3 will 
be assigned to PF-07295324/vehicle and Optional Cohort 4 may be used to study either PF- 
07295324 or PF-07259955. 
 
• The optional cohorts may be used to repeat doses studied in previous cohorts, explore 
lower strength formulation on approximately 20% BSA, or to investigate the safety of 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
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maximum feasible formulation on lower body surface area, or at a less frequent dosing 
regimen on approximately 20% BSA. Participants enrolled in the optional cohorts will 
be randomized 4:2 active: vehicle and will be guided by the same stopping criteria as 
planned cohorts. 
• Participants in optional cohort will be dosed only after review of available safety data 
from a minimum of 4 participants (3 active:1 vehicle), dosed in planned cohort up to 
day 10. 
Dosing will be terminated based on protocol specified individual discontinuation criteria 
(Section 6.5.1, Section 6.5.2). 
 
Planned cohorts assigned to different interventions may progress simultaneously. Similarly, 
optional cohorts assigned to different interventions may progress 
simultaneously (Section 1.2). 
 
The planned duration of participation from screening to follow-up is approximately 
10 weeks. 
 
Data Monitoring Committee or Other Independent Oversight Committee: No 
 
Statistical Methods: 
 
No formal hypothesis testing will be applied to the safety and PK data. The cohort sample 
size has been chosen based on the need to minimize first exposure to humans of a new 
chemical entity and the requirement to provide adequate safety and tolerability assessment 
for each asset. 
 
The safety data and plasma PK parameters will be tabulated and summarized descriptively by 
study intervention, by treatment group and by day, in accordance with Pfizer data standards, 
as data permit. Detailed methodology for descriptive statistical summary will be described in 
statistical analysis plan (SAP). 


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Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
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1.2. Schema 
Figure 1. 
Study Schema 
 
 
 
 
a. PF-07295324 (0.12%)/vehicle in Cohort 1 or PF-07259955 (2%)/vehicle in Cohort 2, will be topically 
applied on approximately 20% body surface area or less than or equal to 4000 cm2, Q12H from D1 to D9; only 
morning (AM) dose will be applied on D10. 
 
b. Based on review of emerging safety from Cohort 1, optional Cohort 3 may be enrolled to repeat the PF- 
07295324 dose studied in Cohort 1, explore lower formulation strength of PF-07295324, topically applied on 
approximately 20% BSA or PF-07295324 (0.12%) on lower body surface area or at a less frequent dosing 
regimen on approximately 20% BSA or less than or equal to 4000 cm2. 
 
c. Based on review of emerging safety assessments from Cohort 1, Cohort 2 and Cohort 3, optional Cohort 
4 may be enrolled to study either PF-07295324 or PF-07259955 by repeating doses studied in previous 
cohort(s), exploring lower formulation strength topically applied on approximately 20% BSA or investigating 
the safety of maximum feasible formulation on lower body surface area or at a less frequent dosing regimen on 
approximately 20% BSA or less than or equal to 4000 cm2. 


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Protocol C4711001 
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1.3. Schedule of Activities 
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
 
1.3.1. Schedule of Activities from Screening to End of Study (EOS): Multiple doses of topical application for 10 days 
Table 1. 
Schedule of Activities from Screening to End of Study 
Visit Identifiera 
Screening 
In patient 
Follow-Up 
Contact/EOS 
Early Termination/ 
Discontinuation 
Days Relative to Day 1 
≤-28 
Day 
-1 
1 
2 
3-4 
5 
6 
7 
8-9 
10 
11 
12b 
41±3c 
Informed consent 
X 
Outpatient visit to CRU 
X 
Inclusion/exclusion criteria 
X 
X 
CRU confinementd 
X 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
X 
Medical/medication history 
(update)e 
X 
X 
Physical examf 
X 
X 
X 
X 
Demography (including height and 
weight) 
X 
Contraception check 
X 
X 
X 
X 
X 
Urine drug testing 
X 
X 
COVID-19 testingg 
X 
X 
COVID-19 temperature check 
X 
X 
Triplicate supine 12-Lead ECGh 
(single at screening and ET) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Supine Vital signsi (Blood pressure 
and pulse rate) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Topical administration of study 
intervention, Q12Hj 
X 
X 
X 
X 
X 
X 
X 
X 
Serious and non-serious adverse 
event monitoring 
X 
X 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
X 
X 
X 


PF-07295324 and PF-07259955 
Protocol C4711001 
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PFIZER CONFIDENTIAL 
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Table 1. 
Schedule of Activities from Screening to End of Study 
 
Visit Identifiera 
Screening 
In patient 
Follow-Up 
Contact/EOS 
Early Termination/ 
Discontinuation 
Days Relative to Day 1 
≤-28 
Day 
-1 
1 
2 
3-4 
5 
6 
7 
8-9 
10 
11 
12b 
41±3c 
Application site monitoringk 
X 
X 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
X 
X 
Serum FSHl 
X 
QuantiFERON TB Gold Test or 
equivalent 
X 
HIV, HCVAb, HBcAb, HBsAg 
X 
Safety Laboratorym 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic blood samplingn 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
a. 
Day relative to start of study intervention (D1). Abbreviations used in this table may be found in Appendix 9. 
b. Participants will be discharged on D12, following completion of all scheduled procedures. Participants who may experience AEs or dermatological 
observations on D12 may be confined to the CRU at the discretion of the PI until AEs or dermatological observations are resolved and may be asked to 
return to the CRU at the discretion of the investigator, for follow-up contact. If unexpected reactions (eg, rash, hives) other than irritation reactions 
outlined in, Section 8.2.5 occur, the body surface area location must be recorded. Appearance of the reactions should be described. 
c. 
Participants will be scheduled for a follow-up phone call on D41±3 days . Additional follow-up contacts may be scheduled at investigator’s discretion, 
including follow-ups to monitor open AEs based on emerging safety data. 
d. Participants will be admitted at least 12 hours prior to dosing. 
e. 
Medical history will be collected at screening and updated on D-1 only. 
f. 
Complete physical examination will be conducted at screening or on D-1 only; otherwise brief physical examination is envisioned for findings during 
previous or new/open AEs, at the discretion of the PI. 
g. Check for exposure to COVID-19 positive participants as per standard CRU protocol. 
h. Singlet measure at screening and early termination only. Triplicate measures at all other times approximately 2-4 minutes apart; ECGs will be measured on 
D1 and D10 as specified in Table 2; ECGs will be measured at pre-AM application on D2, D5 and D7, on D11 at approximately 24H post last application 
and on D12 prior to discharge. 
i. 
Vitals will be collected at screening and early termination; vitals should be measured on D1 and D10 as specified in Table 2; vitals should be collected at 
pre- AM application on D2, D5 and D7; vital signs will be collected on D11 at approximately 24H post last application and D12 prior to discharge. 


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Table 1. 
Schedule of Activities from Screening to End of Study 
 
Visit Identifiera 
Screening 
In patient 
Follow-Up 
Contact/EOS 
Early Termination/ 
Discontinuation 
Days Relative to Day 1 
≤-28 
Day 
-1 
1 
2 
3-4 
5 
6 
7 
8-9 
10 
11 
12b 
41±3c 
j. 
In Cohorts 1 and 2, study intervention/vehicle will be applied, on D1 to D9, Q12H. PM dose will be applied approximately 12±1 hours post-AM dose. On 
D10, study intervention/vehicle will be applied, at AM only. No PM dose will be applied on D10. PF-07295324/vehicle ointment will be applied to 
participants enrolled in Cohort 1 and in optional Cohort 3. PF-07259955/vehicle cream, will be applied to participants enrolled in Cohort 2. PF-07295324 
or PF-0725995 may be studied in optional Cohort 4. 
k. Application sites will be identified at screening. Examination of application sites will be conducted at screening and on D-1. On D1 to D10, skin irritation 
assessment using Draize’s scoring (Table 5) will be performed prior to each application of the investigational product. On D11 (approximately 24H post 
last dose) and on D12 prior to discharge, skin irritation assessment using Draize’s scoring will be performed. Refer to Section 8.2.5. 
l. 
At screening, FSH test will be performed in females only, to confirm postmenopausal status. 
m. Safety labs will be collected at screening, admission (D-1), during in-patient dosing as specified in Table 1, at discharge, and at early termination. 
n. See Table 2 for detailed blood sampling schedule for PK on D1 and D10. Samples will be collected at pre-AM application on D2, D5 and D7. PK sample 
will be collected on D12, prior to discharge. 
CCI 


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1.3.2. Vitals, ECGs, PK, and PD Sampling Schedule on D1 and D10 
 
Table 2. 
Schedule of Activities for Vitals, ECGs,, PK, and PD on Day 1 and Day 10 
 
Abbreviations used in this table may be found in Appendix 9. 
Inpatient 
Days Relative to Day 1 
Day 1 and Day 10 
Hours After topical AM application of PF-07295324 or PF-07259955 
0 
0.5 
1 
2 
4 
6 
8 
10 
12 
24 
Triplicate Supine 12-lead ECG 
X 
X 
X 
X 
X 
X 
Supine Vitals (BP and -pulse rate) 
X 
X 
X 
X 
X 
X 
Study intervention application 
X 
Xa 
Plasma PK collected for the dosed compound 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
a. 
In Cohort 1 and Cohort 2, study intervention/vehicle will be applied topically, on D1 to D9, Q12H. PM dose will be applied approximately 12±1 hours 
post-AM application. On D10, study intervention/vehicle will be applied topically at AM only. No PM application on D10. PF-07295324/vehicle ointment will 
be topically applied to healthy participants enrolled in Cohort 1 and in optional Cohort 3. PF-07259955/vehicle cream will be topically applied to healthy 
participants enrolled in Cohort 2. PF-07295324 or PF-0725995 may be studied in optional Cohort 4. 
CCI 
 


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2. INTRODUCTION 
PF-07295324 and PF-07259955 are JAK inhibitors, and are proposed for topical treatment of 
mild to moderate AD. 
 
2.1. Study Rationale 
The purpose of the study is to evaluate the safety, local and systemic tolerability, and 
pharmacokinetics following multiple doses of topically applied, maximum feasible 
formulation of PF-07295324 (0.12% w/w) and PF-07259955 (2% w/w), on approximately 
20% BSA in healthy adult participants. 
 
As is typical for first-in-human (FIH) studies, the population envisioned for this study will be 
healthy, adult, male and female participants. Female participants will be confirmed to be 
categorized as women of non-childbearing potential (WONCBP) as, at the present time, 
embryo-fetal developmental toxicology studies with PF-07295324 and PF-07259955 have 
not been conducted. In male participants, appropriate measures to minimize potential 
transfer of PF-07295324 and PF-07259955 via semen to partners are expected to be followed 
(refer to Section 10.4). 
 
As this is the first time PF-07295324 and PF-07259955 will be topically administered in 
humans, safety risks to participants will be minimized by conducting the study in in-patient 
settings, with adequate monitoring of local and systemic AEs, safety laboratory parameters, 
12-lead ECGs, and vital signs. Cumulative safety data will be reviewed after the completion 
of each cohort. 
 
The safety, local and systemic tolerability, and PK from this study will support the parallel 
clinical development of PF-07295324 and PF-07259955. 
 
2.2. Background 
Signal Transduction Through The JAK Family Proteins 
The JAK family, including JAK1, JAK2, JAK3 and TYK 2, is a group of cytoplasmic 
tyrosine kinases that mediate signal transduction via interactions with Type 1 and Type 2 
cytokine receptors critical for leukocyte activation, proliferation, survival and function. 
Cytokine receptors demonstrate restricted association with JAKs such that different receptors 
or receptor classes preferentially utilize a given JAK dimer or trimer combination to 
transduce their signal. Following cytokine activation, receptor-associated JAKs are 
phosphorylated and in turn phosphorylate specific sites on the receptor intracellular domain. 
Phosphorylation of specific sites on the intracellular domain of the receptor allows for the 
recruitment of signal transducers and activators of transcription (STATs) that can 
subsequently be phosphorylated by JAKs.1 Phosphorylated STAT molecules are released 
from the receptor, dimerize and translocate to the nucleus where they bind to specific sites on 
the DNA and regulate gene transcription.2 JAK1 pairs with JAK3 to mediate -common 
cytokine signaling and also with JAK2 and/or TYK2 to transmit the signals of additional 
cytokines important in inflammation and immune responses including interleukin (IL)-6, 
interferon (IFN), and IFN. JAK2 homodimers are critical for the signaling of 


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hematopoietic cytokines and hormones including erythropoietin (EPO), IL-3, granulocyte- 
macrophage colony-stimulating factor (GM-CSF) and prolactin. IL-12 and IL-23 are 
dependent on TYK2 and JAK2 for transmitting their signal. 
 
Disease Overview 
Atopic Dermatitis (AD): Multiple pathogenic cytokines are implicated in AD including 
IL-4, IL-13, IL-22, IL-31 and TSLP, which all signal via JAK1. These cytokines prevent 
apoptosis of inflammatory T cell infiltrates in the skin, promote Th2 cell differentiation and 
IgE class switching in B cells, induce epidermal hyperplasia, impair barrier function and 
anti-microbial protein production and act on neurons to promote pruritus .3,4JAK1 inhibition 
by JAK inhibitors is expected to block or attenuate the signaling of these pathogenic 
cytokines. Together with Th2 cells, Th1 and Th17 cells promote inflammation in lesional 
skin in AD patients , and as noted above, differentiation of Th1 and Th17 cells in this 
disorder as well as other diseases, should be reduced by treatment with JAK inhibitors.3,4 
Available Treatments and Rationale for the Development of PF-07295324 and 
PF-07259955 
There are several small and large molecule therapeutics proposed for the treatment of AD 
(corticosteroids, triamcinolone, calcineurin inhibitors, dupilumab etc.). However, there 
remains a medical need for additional safe and effective therapeutic intervention which 
improve the clinical symptoms of AD. PF-07295324 and PF-07259955 are potent and 
selective JAK inhibitors. Both are novel compounds proposed to be administered as topical 
treatments in healthy participants in this study to prepare for future evaluations in AD 
patients. 
 
2.2.1. Nonclinical Pharmacology 
2.2.1.1. Nonclinical Pharmacology for PF-07295324 
PF-07295324, a JAK1, JAK2, and TYK2 inhibitor with selectivity over JAK3, is proposed 
for the dermal treatment of AD. PF-07295324 is expected to block or attenuate the signaling 
of multiple pathogenic cytokines implicated in AD such as IL-4, IL-13, IL-22, IL-31 
and TSLP. These cytokines prevent apoptosis of inflammatory T cell infiltrates in the skin, 
promote Th2 cell differentiation and IgE class switching in B cells, induce epidermal 
hyperplasia, impair barrier function and anti-microbial protein production and act on neurons 
to promote pruritus.3,4 Pharmacology studies were conducted with the free base of PF- 
07295324. 
 
Topical application of PF-07295324 results in diminished expression of pro-inflammatory 
molecules and enhanced expression of the protective skin barrier protein filaggrin in freshly 
excised human skin. Therefore, PF-07295324 is expected to demonstrate beneficial effects in 
the treatment of AD. 
 
In vitro kinase studies showed that PF-07295324 potently inhibits JAK1, JAK2, 
and TYK2 with less activity against JAK3, as well as a good specificity profile over the 
broader kinome. JAK enzymes are critical signaling kinases that regulate the signal 


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transduction pathways triggered by cytokines. In a cellular setting, PF-07295324 potently 
inhibits signaling pathways induced by aforementioned pathogenic cytokines, which are 
mainly responsible for inflammation and pruritus in AD. 
Upon ex vivo topical application to intact human skin that was stimulated with cytokines, 
PF-07295324 inhibited the expression of inflammatory genes and stimulated the expression 
of a skin barrier protein. 
 
2.2.1.2. Nonclinical Pharmacology for PF-07259955 
PF-07259955, a JAK1/TYK2 inhibitor, is being developed for the dermal treatment of AD. 
JAK1 is a critical signaling component which regulates the signal transduction pathways 
triggered by several pathogenic cytokines implicated in the pathogenesis of AD, including 
IL-4, IL-13, IL-22, IL-31 and TSLP. PF-07259955 potently inhibits the signaling of the 
cytokines noted above and blocks the IL-12/Th1 and IL-23/Th17 axes that potentiate the 
pathogenesis of AD. 
 
Topical application of PF-07259955 results in diminished expression of pro-inflammatory 
molecules and enhanced expression of the protective skin barrier protein filaggrin in freshly 
excised human skin. Therefore, PF-07259955 is expected to demonstrate beneficial effects in 
the treatment of AD. 
 
In vitro kinase studies showed that PF-07259955 inhibits JAK1 and TYK2 with lower 
activity against JAK2 and selectivity over JAK3 and the broader kinome. JAK enzymes are 
critical signaling kinases that regulate the signal transduction pathways triggered by 
cytokines. In a cellular setting, PF-07259955 potently inhibits signaling pathways induced by 
aforementioned pathogenic cytokines, which are mainly responsible for inflammation and 
pruritus in AD. 
 
Upon ex vivo topical application to intact human skin that was stimulated with cytokines, 
PF-07259955 inhibited the expression of inflammatory genes and stimulated the expression 
of a skin barrier protein. 
 
2.2.2. Nonclinical Pharmacokinetics and Metabolism 
2.2.2.1. Brief Summary for PF-07295324 
Single-dose PK studies in rats and minipigs indicated a moderate to high systemic clearance 
of PF-07295324 with a moderate Vss, resulting in short t½ (<1 hour). PF-07295324 had an oral 
bioavailability of 32% in rats. Following repeat oral doses in rats or dermal doses in 
minipigs, mean systemic exposure (as assessed by Cmax, AUC24, or Cav) increased with 
increasing dose. In both species, systemic exposures were higher in females as compared 
with males and accumulation was observed after repeat dosing, with accumulation ratios up 
to 89 in male minipigs. The average dermal bioavailability after repeat dose in minipigs was 
10%. 
 
PF-07295324 was moderately bound to plasma proteins with mean fraction unbound values 
of 0.162 (rat), 0.361 (minipig), 0.264 (dog), and 0.148 (human) and preferentially distributed 


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into plasma relative to blood cells in rat, dog and human, with a slight preferential partition 
into blood cells in minipig. 
The primary metabolic pathway for PF-07295324 is through oxygenation and 
glucuronidation. The in vitro metabolic profiles of PF-07295324 were generally similar 
across all species and there were no human unique metabolites. Investigation of the 
metabolism of PF-07295324 in rat, minipig, and dog plasma following oral or dermal dose 
indicated qualitative agreement between in vitro and in vivo metabolism of PF-07295324. In 
minipig plasma, only trace amounts of PF-07295324 and metabolites were detected after 
dermal dosing due to low systemic exposures. 
 
The total CYP and UGT fm were 0.81 and 0.19, respectively. The overall assignment 
of CYP fm was 0.41 by CYP2C9, 0.25 by CYP3A4, and 0.15 remained unassigned. The 
overall assignment of UGT fm was >0.053 by UGT1A4, 0.032 for UGT2B4, 0.027 
by UGT2B7, and 0.078 remained unassigned. 
 
Human clearance of PF-07295324 was predicted to be 7.4 mL/min/kg. Dermal bioavailability 
in humans is predicted to be 10% based on an assumed equivalent bioavailability to minipigs. 
Based on these human predictions, a BID dose of 0.12% (MFD) PF-07295324 applied to 
approximately 20% body surface area is projected to result in an unbound plasma Cav of 0.48 
ng/mL (1.0 nM). Activity of PF-07295324 was demonstrated ex vivo in human skin. 
Compound was topically applied in vitro on freshly excised human skin which was 
subsequently stimulated with an antibody-cytokine cocktail to induce pro-inflammatory 
molecules. Compound caused a dose-dependent inhibition of gene expression of pro- 
inflammatory molecules CXCL10, CCL26 and MMP12 and a dose-dependent stimulation of 
gene expression of filaggrin, a protective skin barrier protein. Maximum effects were 
observed at the PF-07295324 (0.12%) formulation proposed in this study. The topical 
efficacious dose is defined as the maximum feasible, safe and well tolerated formulation (IB 
Section 5.1.2.1.4). 
 
Based on the projected unbound Cav of 0.48 ng/mL (1.0 nM) at the highest planned clinical 
dose, the overall risk of PF-07295324 perpetrating a pharmacokinetic DDI is low. Using a 
static mechanistic model, the risk of PF-07295324 to time-dependently inhibit CYP3A is 
low. 
 
Refer to the PF-07295324 investigator’s brochure (IB) for further details. 
 
2.2.2.2. Brief Summary for PF-07259955 
Following single IV dose, PF-07259955 exhibited moderate to high CL, moderate Vss and 
short t½ (≤ 1 hour) in rats and minipigs. PF-07259955 had an oral bioavailability of 55% in 
rats. Following repeat oral doses in rats or dermal doses in minipigs, mean systemic 
exposures increased with increasing dose and there were no consistent sex related 
differences. Accumulation was only observed in minipigs after repeat dermal doses. 
 
PF-07259955 was moderately bound to plasma proteins with mean fraction unbound values 
of 0.317 (rat), 0.373 (minipig), 0.450 (dog), and 0.345 (human) and preferentially distributed 


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Protocol C4711001 
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PFIZER CONFIDENTIAL 
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into plasma relative to blood cells in rat, dog and human, with a slight preferential partition 
into blood cells in minipig. 
The primary metabolic pathway for PF-07259955 is through monooxygenation. The in vitro 
metabolic profiles of PF-07259955 were generally similar across all species and there were 
no human-unique metabolites. CYP3A4 is predicted to be the major contributor to in vitro 
metabolism of PF-07259955 with a fm value of ≥0.88. Investigation of the metabolism of PF- 
07259955 in rat and minipig plasma following oral or dermal doses indicated qualitative 
agreement between in vitro and in vivo metabolism of PF-07259955. In minipig plasma, only 
trace amounts of PF-07259955 and metabolites were detected after dermal dosing. 
 
Human clearance of PF-07259955 was predicted to be 6.1 mL/min/kg. Dermal 
bioavailability in humans was estimated to be 8.7% based on an assumed equivalent 
bioavailability to minipigs. Based on these human predictions, a BID dose of 2% (MFD) PF- 
07259955 to 20% body surface area is projected to result in a total plasma Cav of 45 ng/mL. 
 
Activity of PF-07259955 was demonstrated ex vivo in human skin. Compound was topically 
applied in vitro on freshly excised human skin which was subsequently stimulated with an 
antibody-cytokine cocktail to induce pro-inflammatory molecules. Compound caused a dose- 
dependent inhibition of gene expression of pro-inflammatory molecules CXCL10, CCL26 
and MMP12 and a dose-dependent stimulation of gene expression of filaggrin, a protective 
skin barrier protein. Maximum effects were observed at the PF-07259955 (2%) formulation 
proposed in this study. The topical efficacious dose is defined as the maximum feasible, safe 
and well tolerated formulation (IB Section 5.1.2.1.4). 
 
Based on the projected total plasma Cav of 45 ng/mL, the overall risk of PF-07259955 
perpetrating a pharmacokinetic DDI is low. Using a static mechanistic model, there is a 
potential for PF-07259955 to inhibit OCT2. 
 
Refer to the PF-07259955 IB for further details. 
 
2.2.3. Nonclinical Safety 
2.2.3.1. Nonclinical Safety for PF-07295324 
The immune and hematolymphopoietic systems were identified as the target organs in the rat 
6-week GLP oral toxicity study with an NOAEL representing 183× exposure margin over the 
predicted human Cav (unbound) of 0.48 ng/mL at the highest planned clinical dose (0.12% 
ointment applied to 20% BSA). Local effects in the skin included exacerbation of a vehicle- 
related dermal findings in the 6-week GLP dermal minipig toxicity study with the NOAEL 
dose of 0.0528 mg/cm²/day representing 8.8× the planned clinical local dose (0.12% ointment 
applied at 2.5 mg/cm2, or 0.006 mg/cm²/day). No adverse findings were observed, either 
systemically or locally, at any dose and, therefore, the 0.12% ointment (0.0528 [0.0264 BID] 
mg/cm²/day dose) was the NOAEL. PF-07295324 has no potential for genotoxicity or 
phototoxicity at the intended clinical doses. 


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Page 24 
 
 
The nonclinical safety profile of this test article has been adequately characterized to support 
progression into clinical trials in adults and adolescents of up to 6 weeks duration. 
 
Further details of the nonclinical safety program are provided in the current Investigator’s 
Brochure. 
 
2.2.3.2. Nonclinical Safety for PF-07259955 
The immune and hematolymphopoietic systems were identified as the target organs in the rat 
6-week GLP oral toxicity study with an NOAEL representing 107× exposure margin over the 
projected human Cav of 45 ng/mL at the highest planned clinical dose (2% cream applied to 
20% BSA). Local effects on the skin were observed at the administration site in the 6-week 
GLP dermal minipig toxicity study with the NOAEL of 0.74 (0.37 BID) mg/cm2/day (2% 
cream), representing 9.3× margin over the highest planned clinical dose (2% cream applied at 
~2 mg/cm2 formulation per dose, or 0.08 [0.04 BID] mg/cm2/day). No test article related 
adverse systemic or local effects were observed in any of the study parameters or endpoints 
evaluated and, therefore, the 2% concentration (0.74 [0.37 BID] mg/cm²/day) was the NOAEL. 
PF-07259955 has no potential for genotoxicity or phototoxicity at the intended clinical doses. 
PF-07259955 has a low-risk potential to induce skin sensitization at proposed clinical doses. 
 
The nonclinical safety profile of PF-07259955 has been adequately characterized to support 
progression into clinical trials in adults and adolescents of up to 6 weeks duration. 
 
Further details of the nonclinical safety program are provided in the current Investigator’s 
Brochure. 
 
2.2.4. Clinical Overview 
As this is a first experience of administration of PF-07295324 and PF-07259955 in humans, 
no clinical data is available to date. 
 
2.3. Benefit/Risk Assessment 
PF-07295324 and PF-07259955 are not expected to provide any clinical benefit to healthy 
participants. This study is primarily designed to investigate safety and local and systemic 
tolerability following topical administration of PF-07295324 (0.12% ointment) or PF- 
07259955 (2% cream), on approximately 20% body surface area, in healthy participants. 
 
Study C4711001 is the first time that PF-07295324 or PF-07259955 will be administered to 
humans. The purpose of the study is to provide the basis for further clinical development of 
PF-07295324 and PF-07259955 as potential new, pharmacological, topical agents for the 
treatment of participants with mild to moderate AD. As of December 2021, no specific 
human risks have been identified; postulated risks based on nonclinical studies are 
summarized in Section 2.2.3. The clinical impact of these potential risks will be minimized 
by conducting the study in in-patient settings, and through adequate safety monitoring of the 
participants following administration of multiple, topical doses of the assigned study 
intervention, PF-07295324 and PF-07259955, as outlined in the Section 1.3 SoA. 


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Due to similarities in the mechanism of action of both PF-07295324 and PF-07259955 and 
common study design elements, a platform FIH trial design has been implemented. This 
platform design will lead to increased efficiency of trial conduct, with no increased safety 
risks to participants enrolled in the study. 
 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of PF-07295324 and PF-07259955 may be found in the respective 
investigator’s brochure, which is the SRSD for this study. 


 
PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
 
2.3.1. Risk Assessment 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention(s) PF-07295324 and PF-07259955 
Skin irritation 
Based on local effects in the skin noted in the 
nonclinical studies 
Local tolerability following topical application 
will be assessed throughout the study by 
evaluation of skin irritation potential using 
Draize’s scoring criteria at frequencies specified 
in the Section 1.3 SoA 
Skin Sensitization 
A low risk for skin sensitization was identified in 
nonclinical studies with PF-07259955 
Participants will be assessed for safety at regular 
intervals throughout the study, including 
assessment of the administration site. Participants 
with any history of angioedema or anaphylaxis to 
topical products or known sensitivity to any of the 
components of the investigational products will 
be excluded from the study. 
Study Procedures 
Adverse events (AEs) related with study 
procedures 
Study procedures may cause AEs from blood 
draws or electrocardiograms monitoring, although 
the potential risks (eg infection, bleeding, 
inflammation of the vein or skin, blood clots, or 
local nerve damage) might be low. 
The protocol is designed to minimize the burden 
on participants while maintaining the integrity of 
the study design to support the 
objectives/endpoints. 
All of the study procedures are only performed by 
qualified medical personnel. Participants will be 
informed of the potential risks. 
Other 
Risks due to COVID-19 
Potential cross-contamination; results could 
potentially be confounded by COVID-19 related 
AEs 
COVID-19 testing according to SoA 
 
 
 
 
PFIZER CONFIDENTIAL 
 
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2.3.2. Benefit Assessment 
PF-07295324 and PF-07259955 are not expected to provide any clinical benefit to healthy 
participants, although clinical assessments including vital signs, ECGs, and laboratory tests 
may be beneficial if they have underlying basic diseases that are measured while reviewing 
the inclusion/exclusion criteria. 
 
2.3.3. Overall Benefit/Risk Conclusion 
At the issuance of this protocol, no human data is available. The study incorporates an 
adequate safety monitoring plan and includes inpatient monitoring of the participants 
following topical administration of the investigational products. The clinical impact of 
potential risks will be minimized through cumulative review of emerging safety and 
tolerability, as the study progresses. 
 
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with PF-07295324 and PF-07259955 are justified by the anticipated 
therapeutic benefits that may be afforded to future trial participants with mild to moderate 
atopic dermatitis. 
 
3. OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• 
To evaluate the safety, and local and 
systemic tolerability, of PF-07295324 and 
PF-07259955, following multiple doses 
of topically administered PF-07295324 or 
PF-07259955, on approximately 20% BSA 
in healthy adult participants. 
• 
Incidence and severity of systemic AEs, safety 
laboratory tests, vital signs (including blood 
pressure and pulse rate), and heart rhythms as 
assessed via 12-lead electrocardiogram (ECG). 
• 
Incidence and severity of application site AEs 
as assessed by Draize score. 
Secondary: 
Secondary: 
• 
To characterize plasma PK following 
multiple topical applications of PF-07295324 
and PF-07259955. 
• 
Plasma PK of multiple topical doses of 
PF-07295324 and PF-07259955, as data permits: 
Day 1: Cmax, Tmax, Cavg, Ctrough, AUCtau 
Day 10: Cmax, Tmax, Cavg, Ctrough, AUCtau, Rac 
(Cmax), Rac(AUCtau), t½, CL/F, and Vz/F 
CCI 


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4. STUDY DESIGN 
4.1. Overall Design 
C4711001 is an investigator- and participant-blinded, interventional, randomized, vehicle- 
controlled, Phase 1 study to evaluate the safety, and local and systemic tolerability and 
pharmacokinetics of maximum feasible formulation of topical JAK inhibitors, PF-07295324 
(0.12%) and PF-07259955 (2%) in healthy adult participants. 
 
This study will enroll healthy adult participants in ≤4 cohorts: 2 planned cohorts and 2 
optional cohorts. Approximately 6 participants will be enrolled in each cohort, randomized as 
4 active:2 vehicle. Cohort 1 and the optional Cohort 3 will be assigned to PF- 
07295324/vehicle, administered topically as an ointment. Cohort 2 will be assigned to PF- 
07259955/vehicle administered topically as a cream. PF-07295324 or PF-0725995 may be 
studied in optional Cohort 4. 
 
Participants will be enrolled in the optional cohorts in a sequential design to the respective 
planned cohort, as shown in Section 1.2. Planned cohorts assigned to different interventions 
may progress simultaneously. Similarly, optional cohorts assigned to different interventions 
may progress simultaneously (Section 1.2). 
 
Healthy adult participants will be screened for eligibility criteria within 28 days prior to the 
administration of the first dose in each part of the study. Participants enrolled in 1 cohort of 
this study will not be allowed to enroll in any other cohorts of the study. Participants 
enrolled in each of the cohorts will be discharged following completion of all scheduled 
assessments as specified in the SoA. 
 
Participants confirming eligibility according to Section 5 will be admitted to the CRU on 
Day -1. On Day 1, application sites of all participants will be assessed, prior to the 
administration of study intervention/vehicle. Dermal reactions at the application site will be 
assessed clinically using a visual grade that rates the degree of erythema, edema, and other 
signs of skin irritation. Participants enrolled in Cohort 1 and Cohort 2, with no dermal site 
reactions at pre-dose on Day 1, will receive multiple topical doses of study intervention or 
vehicle, Q12H from Day 1 to Day 9, and only AM application on Day 10. All AM doses will 
be administered approximately 60 minutes following shower, if participants choose to 
shower; all PM doses will be administered approximately 12±1 hour post-AM dose. 
Participants will be discharged on Day 12 following the completion of all scheduled 
procedures as per SoA. Participants will be scheduled for a follow-up phone contact on 
Study Day 41±3 days. 
 
Up to 2 optional cohorts (Cohort 3 and Cohort 4) of up to 6 participants/cohort may be 
enrolled in this study. Participants enrolled in the optional cohort will be randomized to 
either active or vehicle (4:2). The optional cohorts may be used to repeat the doses studied in 
previous cohorts, explore lower strength formulations on approximately 20% BSA, or to 
repeat the maximum feasible formulation on lower body surface area, or to administer 
maximum feasible formulation at a less frequent dosing regimen on approximately 20% 


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BSA. Participants enrolled in the optional cohorts will be guided by the same stopping 
criteria as the planned cohorts. 
 
If a participant has any clinically significant, study related abnormalities at the conclusion of 
a scheduled inpatient portion of the study, the Pfizer medical monitor (or designated 
representative) should be notified and the participant may be asked to remain in the CRU 
until such abnormalities are deemed not clinically significant, or it is safe for outpatient 
follow-up. Participants who experience a treatment-related AE will continue to be followed 
to resolution or stabilization of the event as agreed upon by the investigator and sponsor. 
Participants who discontinue for non-safety related reasons prior to end of the study may be 
replaced, at the discretion of the principal investigator (PI) and the sponsor. 
 
The planned duration of participation from screening to follow-up is approximately 
10 weeks. 
 
4.2. Scientific Rationale for Study Design 
C4711001 is a Phase 1, First-in-Human (FIH) study. The purpose of this study is to 
investigate the local and systemic tolerability of multiple topical applications of PF- 
07295324 and PF-07259955 on approximately 20% body surface area, in healthy adult 
participants. 
 
The intended route of administration for future clinical development of PF-07295324 and 
PF-07259955 is topical, which is the same route that will be tested in this study. 
 
As is typical for FIH studies, the population envisioned for this study will be healthy male 
and female participants. Female participants will be confirmed to be categorized as women of 
non-childbearing potential as, at the present time, embryo-fetal developmental toxicology 
studies with PF-07295324 and PF-07259955 have not been conducted. Appropriate measures 
to minimize potential transfer of PF-07295324 and PF-07259955 via semen to partners are 
expected to be followed by male participants (refer to Section 10.4.1). 
 
PF-07295324 and PF-07259955 are both potent JAK inhibitors demonstrating similar non- 
clinical pharmacology. The objective of the FIH study is to evaluate the safety and 
tolerability of the two topical JAK inhibitors. As the FIH study of the two topical JAK 
inhibitors will use common study design elements including study population, 
inclusion/exclusion criteria, sample size, randomization ratio, route of administration and 
frequency of dosing. Due to similar non-clinical safety outcomes, both JAK inhibitors will 
be monitored using identical safety monitoring plan and individual discontinuation criteria in 
FIH study. 
 
Due to a common framework described above, this FIH study of both the JAK inhibitors PF- 
07295324 and PF-07259955, has been designed under 1 single Phase 1 study 
protocol, C4711001. This design will lead to increased efficiencies by optimizing the use of 
operational resources leading to simultaneous characterization of the two topical JAK 
inhibitors, and with no increased safety risks to participants enrolled in the trial. 


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To permit an unbiased assessment of safety, participants will be randomized to active or 
vehicle in a ratio of 4 active: 2 vehicle. The participants and clinical research unit (CRU) 
staff (except specific personnel involved in the preparation of doses) will be blinded to 
treatment assignment in each cohort, to permit an unbiased assessment of safety and 
tolerability. A limited number of team members will be unblinded to permit real time 
monitoring of emerging safety. 
 
As this is a first experience of PF-07295324 and PF-07259955 in humans, risks to study 
participants will be minimized by conducting dosing in an inpatient setting and with cautious 
inpatient monitoring. Monitoring of local and systemic AEs, clinical safety laboratory tests 
(Appendix 2), vital signs, electrocardiograms (ECGs), and physical examinations will 
provide essential data to investigate the safety of PF-07295324 and PF-07259955 following 
topical application. 
CCI 
 
 
4.2.1. Diversity of Study Population 
Not applicable 
 
4.2.2. Choice of Contraception/Barrier Requirements 
Studies to evaluate the development toxicity of PF-07259955 and PF-07295324 have not 
been conducted. Therefore, the use of a highly effective method of contraception is required 
(see Appendix 4). 
 
4.2.3. Collection of Retained Research Samples 
Retained Research Samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention. 
 
4.3. Justification for Dose 
As this is a first experience of administering topical PF-07295324 and PF-07259955 in 
humans, no prior clinical data is available to guide topical dose selection. Maximum feasible 
formulations of PF-07295324 (0.12%) and PF-07259955 (2%) will be evaluated in Cohort 1 
and Cohort 2, respectively, as shown in the Schema. The vehicle formulations have been 
optimized using excipients that are precedented and are below the limits of toleration; 
therefore vehicles are expected to be well-tolerated. Prior precedence with topical JAKs (in 
mild to moderate AD) and oral JAK inhibitors (in HVs) enables progression of a JAK 
inhibitor in humans at maximum feasible topical formulation. 


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The maximal BSA for application area has been determined to be approximately 20%, to 
adequately support early clinical development in mild-to-moderate AD participants. 
Systemic exposures of the maximum feasible formulation on approximately 20% BSA and 
corresponding safety multiples of PF-07295324 and PF-07259955 have been projected 
below. 
4.3.1. Dose rationale for PF-07295324 
Solubility and chemical stability of PF-07295324 with topical excipients were key drivers to 
nominate the maximal strength ointment formulation of 0.12% (w/w). 
 
The PF-07295324 formulation when applied to human skin (stimulated ex-vivo), caused 
dose-dependent inhibition of gene expression of pro-inflammatory molecules CXCL10, 
CCL26 and MMP12 stimulation of gene expression of filaggrin, a protective skin barrier 
protein. Maximum effects were observed at the formulation strength proposed in this study. 
(IB Section 5.1.2.1.4. and summarized in protocol Section 2.2.1). 
 
Steady state systemic exposures following topical administration of PF-07295324 (0.12%), 
once daily or Q12H, on approximately 20% BSA, have been projected assuming ointment 
application rate of approximately 2.5 mg/cm2, dermal availability of approximately 10%, 
(similar to that estimated in minipigs at steady-state, following topical administration of 
0.12% PF-07295324 ointment, BID) and predicted human hepatic clearance of 7.4 
mL/min/kg (Section 2.2.2.1). The projected steady-state systemic exposures following 
topical administration of 0.12% PF-07295324, are summarized in Table 3. 
 
Table 3. 
Projected steady-state exposures and Safety Margins Following 
Administration of Multiple Topical Doses of PF-07295324 (0.12%), once daily 
or twice daily on 10-20% BSA, in Healthy Adult Participants 
 
COH. 
FORM. 
STRENGTH 
(%) 
QD/ 
BID 
%BSA 
TDDa 
(mg) 
DOSE 
SYS. b 
(mg) 
AUC24b 
(ng*h/mL) 
uCavg 
(ng/mL) 
uCavg.IFNꝩc 
uCAVG.SMd 
Coh. 1 
0.12 
BID 
20 
24 
2.4 
77 
0.48 
18 
183 
Optional 
Coh. 3 
0.12 
BID 
10 
12 
1.2 
39 
0.24 
35 
367 
Optional 
Coh. 3 
0.12 
QD 
20 
12 
1.2 
39 
0.24 
35 
367 
a. 
Total daily dose calculated as appropriate for once daily or twice daily application and as a product of formulation 
strength and body surface area, assuming an ointment application rate of approximately 2.5 mg/cm2. 
b. 
Assuming median healthy participants BW ~70 kg, unbound exposures were predicted using CLp=30.8 L/h, Vd=56 L, 
Fa.Fg=1, F=0.1, and in vitro fraction unbound in human plasma fu,p=0.148; MW = 467.5; 1 ng/mL unbound PF- 
07295324 is equivalent to 2.08 nM. 
c. 
Multiples have been calculated relative to PF-07295324 unbound plasma IFNꝩ IC50 of 18 nM. 
d. 
Margins have been calculated relative to PF-07295324 NOAEL unbound Cavg=88 ng/mL in 6 week oral GLP toxicology 
study in rat; systemic safety margins have been calculated based on unbound plasma exposures. 
 
 
As summarized in Table 3, following topical administration of maximum feasible formulation 
(0.12%) of PF-07295324, Q12H, on approximately 20% BSA the projected steady-state 
average unbound plasma concentration (Cavg) is 0.48 ng/mL. 


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Based on the projected steady-state systemic exposure [0.48 ng/mL (1 nM) is ~18-fold below 
the unbound IFN IC50 (18 nM)] following topical administration of PF-07295324 (0.12%, 
Q12H, 20%BSA). 
 
This highest projected average unbound exposure is approximately 183-x below the rat 
unbound NOAEL Cavg of 88 ng/mL. In minipigs, topical administration of an equivalent dose 
resulted in minimal, non-adverse local irritation (Section 2.2.3.1). The NOAEL in the 
PF-07295324 pivotal 6-week dermal toxicity study in minipigs was 0.0528 mg/cm2/day, 
resulting in an ~8.8-x dose margin based on an anticipated clinical application rate of 
2.5 mg/cm2 and dose of 0.006 mg/cm2/day (0.12% ointment, BID). 
Overall, multiple topical administrations of PF-07295324 (0.12%), in healthy adult 
participants is expected to be safe and well tolerated, locally and systemically. 
 
4.3.2. Dose rationale for PF-07259955 
Solubility and chemical stability of PF-07259955 with topical excipients were key drivers to 
nominate the maximal strength cream formulation of 2% (w/w). 
The PF-07259955 formulation when applied to human skin (stimulated ex-vivo), caused 
dose-dependent inhibition of gene expression of pro-inflammatory molecules CXCL10, 
CCL26 and MMP12 stimulation of gene expression of filaggrin, a protective skin barrier 
protein. Maximum effects were observed at the formulation strengths proposed in this study. 
(IB Section 5.1.2.1.4. and summarized in protocol Section 2.2.1). 
 
Steady state systemic exposures following topical administration of PF-07259955, once daily 
or Q12H, on approximately 20% body surface area, have been projected assuming cream 
application rate of approximately 2 mg/cm2, dermal availability of approximately 8.7%, 
(similar to that estimated in minipigs at steady-state, following topical administration of 2% 
PF-07259955 cream, BID) and predicted human hepatic clearance of 6.1 mL/min/kg 
(Section 2.2.2.2). The projected steady-state systemic exposures following topical 
administration of 2% PF-07259955, are summarized in Table 4. 


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Table 4.  Projected steady-state exposures and Safety Margins Following Administration 
of Multiple Topical Doses of PF-07259955 (2%), once daily or twice daily on 10- 
20% BSA, in Healthy Adult Participants 
 
COH. 
FORM. 
STRENGTH 
(%) 
QD/ 
BID 
%BSA 
TDDa 
(mg) 
DOSE 
SYS. b 
(mg) 
AUC24b 
(ng*h/mL) 
uCAVG 
(ng/mL) 
uCavg.IFNc 
uCAVG.SMd 
Coh. 2 
2 
BID 
20 
320 
28 
1100 
16 
3.7 
110 
Optional 
Coh. 4 
2 
BID 
10 
160 
14 
540 
7.8 
7.7 
220 
Optional 
Coh. 4 
2 
QD 
20 
160 
14 
540 
7.8 
7.7 
220 
a. Total daily dose calculated as appropriate for once daily or twice daily application and as a product of formulation strength 
and body surface area, assuming an ointment application rate of approximately 2 mg/cm2. 
b. Assuming median healthy participants BW ~70 kg, unbound exposures were predicted using CLp=26 L/h, Vd=77 L, Fa.Fg=1, 
%F=8.7, and in vitro fraction unbound in human plasma fu,p=0.345; MW = 417.5; 1 ng/mL unbound PF-07259955 is equivalent 
to 2.4 nM. 
c. Multiples have been calculated relative to PF-07259955 unbound plasma IFN IC50 of 143 nM. 
d. Margins have been calculated relative to PF-07259955 NOAEL unbound Cavg=1691 ng/mL in 6 week oral GLP toxicology 
study in rat; systemic safety margins have been calculated based on unbound plasma exposures. 
As summarized in Table 4, following topical administration of maximal feasible formulation 
(2%) of PF-07259955, Q12H, on approximately 20% BSA, the projected average steady state 
unbound plasma concentration (Cavg) is approximately, 16 ng/mL (38.4 nM). 
 
Based on the projected steady-state systemic exposure [16 ng/mL (38.4 nM) is ~3.7-fold below 
the unbound IFN IC50 (143 nM)], following topical administration of PF-07259955 (2%, 
Q12H, 20%BSA). 
 
This highest projected exposure is approximately 110-x below the rat unbound NOAEL Cavg 
of 1691 ng/mL. Similarly, minimal, non-adverse local irritation is anticipated at this 
maximum feasible formulation based on 6 week dermal toleration assessment in minipigs 
(Section 2.2.3.2). The NOAEL in the PF-07259955 pivotal 6-week dermal toxicity study in 
minipigs was 0.74 mg/cm2/day, resulting in an ~9.3x dose margin based on an anticipated 
clinical application rate of 2 mg/cm2 and dose of 0.08 mg/cm2/day (2% cream, BID). 
Overall, multiple topical administrations of PF-07259955 (2%), in healthy adult participants 
are expected to be safe and well tolerated, locally and systemically. 
 
Beyond Cohort 1 and Cohort 2, up to 2 optional cohorts (Cohort 3 and potentially Cohort 4) 
of up to 6 healthy adult participants in each cohort may be enrolled in this study. The optional 
cohorts may be used to repeat the doses studied in previous cohorts, explore lower formulation 
strength, or repeat the 0.12% formulation strength on lower body surface area, or at less 
frequent dosing interval on approximately 20% BSA. All cumulative safety data from Cohort 
1 and Cohort 2 will be used to determine the formulation strength, %BSA, and dosing regimen 
to be administered to participants enrolled in optional cohorts. The formulation strengths and 
frequency of dosing of PF-07295324 or PF-07259955 to be investigated in the optional Cohort 
3 and/or Cohort 4 will not exceed that of Cohort 1 or Cohort 2. 


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4.4. End of Study Definition 
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last scheduled follow-up contact shown in the SoA. 
 
The end of the study is defined as the date of the final follow-up contact shown in the SoA 
for the last participant in the trial. 
 
5. STUDY POPULATION 
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
 
5.1. Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
 
Age and Sex: 
 
1. Healthy (except obese) female participants of non-childbearing potential and/or male 
participants, at the time of screening, must be 18 to 60 years of age, inclusive, at the 
time of signing the informed consent document (ICD). 
 
• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants of non-child bearing potential. 
 
Type of Participant and Disease Characteristics: 
 
2. Male and female of non-child bearing potential participants, who are healthy as 
determined by medical evaluation including medical history, physical examination, 
vital assessments, 12-lead ECGs, and laboratory tests. 
 
3. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures. 
 
Weight: 
 
4. Body mass index (BMI) of 17.5 to 35 kg/m2; and a total body weight >50 kg (110 lb). 


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Informed Consent: 
 
5. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol. 
 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
 
Medical Conditions: 
 
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, 
immunological/rheumatological, or allergic disease (including drug allergies, but 
excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 
 
2. Participants who have any visible skin damage or skin condition (eg sunburn, 
excessively deep tans, uneven skin tones, tattoos, scars, excessive hair, numerous 
freckles, or other disfigurations) in or around the application site which, in the 
opinion of the investigative personnel, will interfere with the evaluation of the test 
site reaction. 
 
3. Participants who have a history of or have active AD/eczema/urticaria. 
 
4. Evidence of active or latent or inadequately treated infection with Mycobacterium 
tuberculosis (TB) as defined by both of the following: 
 
• A positive QuantiFERON-TB Gold In-tube or equivalent test (QFT). 
• History of either untreated or inadequately treated latent or active TB infection, or 
current treatment for the same. 
 
5. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, 
hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or 
hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed. As an exception 
a positive HBsAb test due to hepatitis B vaccination is permissible. 
 
6. Have a history of systemic infection requiring hospitalization, parenteral 
antimicrobial therapy, or as otherwise judged clinically significant by the investigator 
within 6 months prior to Day 1. 
 
7. A history (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes 
zoster. 


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8. Acute disease state (unstable medical condition such as nausea, vomiting, fever or 
diarrhea, etc) within 7 days of Day 1. 
 
9. Have any malignancies or have a history of malignancies with the exception of 
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the 
skin. 
 
10. Have a first-degree relative with hereditary immunodeficiency. 
 
11. A history of any lymphoproliferative disorder (such as Epstein Barr Virus [EBV] – 
related lymphoproliferative disorder), history of lymphoma, leukemia, malignancies 
or signs and symptoms suggestive of current lymphatic disease. 
 
12. Have undergone significant trauma or major surgery within 4 weeks of screening. 
 
13. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality or other conditions or 
situations related to COVID-19 pandemic (eg. Contact with positive case, residence, 
or travel to an area with high incidence) that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for 
the study. 
 
Prior/Concomitant Therapy: 
 
14. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. (Refer to Section 6.8 Concomitant Therapy for additional details). 
 
15. Participants who are vaccinated with vaccines that have live components (or live 
attenuated vaccines) within the 6 weeks prior to the first dose of PF-07295324/vehicle 
or PF-07259955/vehicle or who are expected to be vaccinated during treatment or 
during follow-up period. 
 
NOTE regarding COVID-19 vaccines with authorization or approval for 
emergency use: 
 
There is no requirement for washout of COVID-19 vaccines prior to the first dose of 
PF-07295324/vehicle or PF-07259955/vehicle if the vaccine is not live attenuated 
(eg, mRNA, utilizing a viral vector, inactivated virus).There is no protocol-specified 
requirement for the interruption of IP dosing prior to or after vaccination if the 
COVID-19 vaccine is not live attenuated. 
 
16. Participants in any cohort of this study can only be randomized and receive the IP in 
only 1 cohort of this study. 


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Prior/Concurrent Clinical Study Experience: 
 
17. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of study intervention 
used in this study (whichever is longer). 
 
Diagnostic Assessments: 
 
18. A positive urine drug test. 
 
19. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at 
least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg 
(diastolic), the BP should be repeated 2 more times and the average of the 3 BP 
values should be used to determine the participant’s eligibility. 
 
20. Baseline 12-lead electrocardiogram (ECG) that demonstrates clinically relevant 
abnormalities that may affect participant safety or interpretation of study results 
(eg, baseline QTcF interval >450 msec, complete left bundle branch block [LBBB], 
signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes 
suggestive of myocardial ischemia, second- or third-degree atrioventricular [AV] 
block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected 
QT interval is >450 msec, this interval should be rate-corrected using the Fridericia 
method and the resulting QTcF should be used for decision making and reporting. If 
QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 
2 more times and the average of the 3 QTcF or QRS values should be used to 
determine the participant’s eligibility. Computer-interpreted ECGs should be 
overread by a physician experienced in reading ECGs before excluding participants. 
 
21. 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: 
 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 
≥1.5 × upper limit of normal (ULN); 
 
• Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is ≤ ULN. 
 
Other Exclusions: 
 
22. 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). 


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23. Use of tobacco/nicotine containing products more than 5 cigarettes/day. 
 
24. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing. 
 
25. History of serious adverse reactions or hypersensitivity to any topical drug; or known 
allergy to any of the test product(s) or any components in the test product(s) or 
history of hypersensitivity; or allergic reactions to any of the study preparations as 
described in the PF-07295324 IB and PF-07259955 IB. 
 
26. Not willing to refrain from shaving, the use of depilatories or other hair-removal 
activities, antiperspirants, lotions, skin creams, fragrances or perfumes, or body oils 
(eg, baby oil; coconut oil), use of hair products, hair gels, and hair oil in the treatment 
areas for 48 hours prior to admission to the CRU and for the duration of the stay in 
the CRU. 
 
27. Unwilling or unable to comply with the criteria in the Lifestyle Considerations 
section of this protocol. 
 
28. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members. 
 
5.3. Lifestyle Considerations 
The following guidelines are provided: 
 
5.3.1. Meals and Dietary Restrictions 
• Participants must abstain from all food and drink (except water) at least at least 4 
hours prior to any safety laboratory evaluations conducted at pre-AM application. 
 
• Otherwise, water, meals, and snacks may be consumed without restriction. 
5.3.2. Caffeine, Alcohol, and Tobacco 
• Participants will abstain from caffeine-containing products for 24 hours prior to the 
start of dosing and during confinement in the CRU. 
 
• Participants will abstain from alcohol for 24 hours prior to admission to the CRU and 
continue abstaining from alcohol until collection of the final PK sample. 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. 


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5.3.3. Activity 
• Showering/Bathing: Participant’s dosing areas of skin are required to be dry for at 
least 30 minutes prior to each study drug application. To help facilitate this, 
participants will not be permitted to shower or bathe within 1 hour prior to and 
4 hours after any study drug dose application. Participants are not required to shower 
or bathe prior to each dose application. If participants choose to shower or bathe, it 
will occur at least 1 hour prior to the AM and PM dose. 
 
• Participant should not use any products in the area where the investigational product 
is applied during confinement in the CRU. 
 
• Participants should be encouraged not to touch the area of application. 
• Participants should be encouraged not to put hands in the mouth to avoid ingestion of 
investigational product. 
 
• Participants should avoid wiping the investigational product off the skin. 
• 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. 
 
• Participants are permitted to participate in light recreational activities during the study 
(eg, watching television, reading). Following application, study participants are 
required to wear loose-fitting clothing and avoid activity for at least 4 hours post AM 
and PM dose, to minimize the study medication being wiped off the skin or the 
treated areas to become occluded. 
 
5.3.4. Contraception 
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4) and will confirm that the participant has been instructed in its 
consistent and correct use. At time points indicated in the schedule of activities (SoA), the 
investigator or designee will inform the participant of the need to use highly effective 
contraception consistently and correctly and document the conversation and the participant’s 
affirmation in the participant’s chart (participants need to affirm their consistent and correct 
use of at least 1 of the selected methods of contraception) considering that their risk for 
pregnancy may have changed since the last visit. In addition, the investigator or designee will 
instruct the participant to call immediately if the selected contraception method is 
discontinued or if pregnancy is known or suspected in the participant or partner. 


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5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently entered in the study. Screen failure data are collected and remain as 
source and are not reported to the clinical database. Individuals who do not meet the criteria 
for participation in this study (screen failure) may be rescreened and enrolled in a subsequent 
group or cohort. 
 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol. 
 
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention. 
 
6.1. Study Intervention(s) Administered 
For this study, the investigational products are PF-07295324 (0.12%), ointment and 
PF-07259955 (2%), cream, as well as the corresponding vehicles for each IP. 
 
Both the IPs (PF-07295324 and PF-07259955) and vehicles (ointment and cream) will be 
supplied by Pfizer to the CRU as packaged 60 gram tubes and labeled according to local 
regulatory requirements in an unblinded fashion. 
 
Both the IPs (PF-07295324 and PF-07259955) and vehicle doses will be prepared by the 
unblinded CRU pharmacist and provided to the blinded investigational site staff. 
 
During the stay in the CRU, study drug applications will be performed by trained study staff 
to ensure proper study drug application. 
 
6.1.1. Administration 
6.1.1.1. PF-07295324 and PF-07259955 Administration 
The IP will be applied in blinded fashion, at the CRU. All applications of the IP will be 
dispensed and applied by study site staff from D1 AM through D10 AM dose. For Cohort 1 
and Cohort 2, topical formulation will be applied Q12H on D1-D9 to the area identified on 
D-1 or D1. Only the AM dose will be applied on D10. Every effort must be made for the 
AM applications on D2 to D10 to be completed approximately 24±2 hour intervals from the 
recorded time of completion of the D1 dose application, for each participant. The PM dose 
application on D1 through D9 will be applied approximately 12±1 hour after the recorded 
time of completion of each of the AM dose application, for each participant. 
 
For optional Cohort 3 and Cohort 4, formulation may be of a lower strength or equal to that 
of the planned cohort; administration procedures will be similar to that of planned cohorts. If 
study intervention in the optional cohort/s is once daily, formulation will be applied at AM 
only, from D1 to D10. 


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The per application dose will be calculated using the formula provided below in 
Section 6.1.1.2. The intended application rate is approximately 2.5 or 2 mg/cm2 for PF- 
07295324 or PF-07259955, respectively. The IP should be applied evenly to all pre-specified 
areas. The per application dose will be expressed as the weight of ointment or cream in 
grams. The per application dose will remain fixed and the IP will be applied to the areas 
identified on Day 1. 
 
In order to standardize the conditions on PK sampling days, all participants will be required 
to refrain from lying down for at least 4 hours post application (except when required for BP, 
pulse rate, and ECG measurements). 
 
6.1.1.2. Calculation of Per Application Dose 
The per application dose (expressed in g) will be calculated by study site staff, for each 
participant, using the formula below: 
 
BSA × Application rate (g/cm2) = Weight of investigational product (in g) per application. 
where BSA is less than or equal to 4000 cm2 () and application rate is 2.5 mg/cm2 (for 
cohorts assigned to PF-07295324/vehicle) and 2 mg/cm2 (for cohorts assigned to PF- 
07259955/vehicle). 
 
6.1.1.3. Application of Investigational Product 
Before the D1 AM dose is applied for each participant, the designated areas for treatment 
will be identified on D-1 or D1 and documented in the participants’ study records. The 
treatment areas will be mapped using surgical markers (on D-1 or D1) to outline areas to 
ensure they remain the same throughout the double-blind treatment period. For each 
subsequent investigational product application, study site staff will refer to the documented 
locations as determined on D-1 or D1. 
 
To standardize the application, the investigational products will be applied to a BSA of 
approximately 20% (±10%) or less than or equal to 4000 cm2±400, for 10 consecutive days, 
at an approximate formulation rate of 2.5 mg/cm2 or 2 mg/cm2 for PF-07295324 or PF- 
07259955, respectively. 
 
For participants in Cohort 1 and Cohort 2, the application area will include the back as well 
as other extremities identified by the investigator. 
 
For participants in optional Cohort 3 and Cohort 4, if study intervention is planned for lower 
body surface areas, smaller treatment area may be mapped for topical administration. 


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Wearing gloves, study site staff will apply the formulation to the areas determined on D-1 or 
D1. Study drug will be applied as a thin layer on participants’ skin. Care must be taken to 
avoid study drug contamination of designated venous access areas used for PK sampling, by 
leaving an untreated margin of at least 5 cm radius around each venipuncture site. Following 
investigational product application, participants will be instructed to wear loose fitting 
clothing, to not wipe investigational product off the skin, and to refrain from bathing, sauna 
or washing the treated areas within 4 hours after application. At 4 hours postdose, 
investigational product will be wiped from all application sites, with a clean towel. 
 
6.2. Preparation, Handling, Storage, and Accountability 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business. 
 
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual. 
 
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label. 
 
5. Study interventions should be stored in their original containers and in accordance 
with the labels. 
 
6. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record. 


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7. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. All destruction must be adequately 
documented. If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer. 
 
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual. 
 
6.2.1. Preparation and Dispensing 
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff. Dispensing is defined as the provision of study intervention, concomitant treatments, 
and accompanying information by qualified staff member(s) to a healthcare provider, 
participant in accordance with this protocol. Local health authority regulations or investigator 
site guidelines may use alternative terms for these activities. 
 
Prior to application, the per application dose will be carefully weighed out by CRU pharmacy 
staff. All study drug accountability will be recorded on the Investigational Product 
Accountability Log (IPAL). 
 
PF-07295324 and PF-07259955 will be prepared by qualified unblinded site pharmacist 
according to the IP manual. Blinded investigational product will be applied to the 
participant. 
 
6.3. Measures to Minimize Bias: Randomization and Blinding 
6.3.1. Allocation to Study Intervention 
The investigator will assign participant numbers to the participants as they are screened for 
the study. Pfizer will provide a randomization schedule to the investigator and in accordance 
with the randomization code, the participant will receive the study treatment regimen 
assigned to the corresponding randomization number. 
 
Investigators and participants will remain blinded to each participant’s assigned study 
intervention throughout the course of the study. In order to maintain this blind, an otherwise 
uninvolved third party (for example, pharmacist) will be responsible for the preparation and 
dispensing of all treatments, according to the randomization schedule and assigned treatment 
for the individual participant. 
 
6.3.2. 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 


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investigator should make every effort to contact the Medical Monitor prior to unblinding a 
participant’s treatment assignment unless this could delay further management of the 
participant. If a participants’ 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 data collection tool (DCT). 
 
CRU Pharmacy must ensure that any opened randomization information is secured 
appropriately again after consultation. 
 
Blinding codes should be broken only under exceptional circumstances when knowledge of 
the actual treatment code is absolutely essential for further management of the participant. 
Investigators are encouraged to discuss with a member of the study team if they believe that 
unblinding is necessary. 
 
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 will be blinded to study 
treatments. A limited number of Pfizer study team personnel will be unblinded to participant 
treatments in order to permit real-time interpretation of the safety data and provide 
information necessary to determine dose and regimen of the optional cohort, if enrolled. 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. 
 
6.4. Study Intervention Compliance 
Investigational product will be applied under the supervision of investigator site personnel. 
The application site of each participant will be examined following dosing to ensure the 
investigational product was topically applied. The date and time of each dose administered 
will be recorded in the source documents. 
 
6.5. Dose Modification 
No dose modification is anticipated for Cohort 1 and Cohort 2 in this study. Dose and dosing 
regimen in Cohort 3 and Cohort 4 may be determined based on review of emerging data from 
Cohort 1 (for Cohort 3 only) and Cohort 1, Cohort 2 and Cohort 3 (for Cohort 4 only). 
 
6.5.1. Dose Stopping Rules 
No dose escalation is planned for this study. 
 
The dosing will be terminated based on the following criteria: 
 
• If 50% or more of the participants receiving active drug (but not participants 
receiving placebo) develop similar clinically significant laboratory, ECG, or vital sign 
abnormalities, in the same organ class, indicating dose-limiting intolerance. 


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• Severe nonserious AEs, considered as, at least, possibly related to study intervention 
administration, in 2 participants at a given dose level (but not participants receiving 
placebo), independent of within or not within the same system organ class, indicating 
dose-limiting intolerance. 
 
• Dosing will be paused for any SAE that occurs in a participant receiving active 
treatment until causality is fully assessed by the PI and sponsor. Dosing may resume 
if the SAE is determined to be not drug-related by the PI and sponsor. If the SAE is 
determined to be either drug-related or unknown, either dosing will cease or the SAE 
will be evaluated by the sponsor’s protocol review committee (or similar review 
group), which is independent of the study team and investigators. If the protocol 
review committee determines that dosing may resume, a plan that mitigates risks to 
participants with the resumption of dosing will be implemented. Such a plan could 
include a revision of inclusion/exclusion criteria, repeating or reducing the dose, or 
adding appropriate safety monitoring. 
 
• Draize score will be incorporated in individual dose application decisions. The dose 
will not be considered well-tolerated and application of corresponding IP will be 
terminated if: 
 
• Persistent Draize scoring of ≥3 in more than 50% participants in each cohort. 
• Persistent Draize score of 4 in 2 or more participants in a cohort. In addition, the 
study will be paused for further assessment of any Draize score of 4. 
 
• Clinically significant skin abnormalities following application of the IP (based on 
the judgment of the medical provider/investigator) in 2 or more participants in a 
cohort. These include persistent moderate to severe skin findings at the site of 
active drug application: edema, papules, vesicles, bullae, weeping, fissuring, and 
erosions. 
 
• Within a participant, “Persistent” is defined as the presence of skin findings in 
at least 2 consecutive assessment periods at least 8 hours apart. 
 
• Other findings that, at the discretion of the study team and investigator, indicate that 
dosing should be halted. 
 
Optional cohort dosing will occur after review of all available safety data in a minimum of 
4 participants (3 active: 1 vehicle) dosed in Cohort 1 , Cohort 2 and Cohort 3 (for Cohort 4 
only) up to 10 days post-dose. 


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6.5.2. Individual Stopping Rules 
If an individual participant exceeds any of the following, the participant will be discontinued 
from the study and will enter early termination visit as per SoA: 
 
• Any of the following values (to be confirmed at 24 hours [±8 hours window]): 
• ECG changes (as described in Section 7.1.1), potential acute kidney injury (as 
described in Section 7.1.2), and potential drug-induced liver injury (as described 
in Appendix 6); 
 
• Any laboratory values or clinically significant findings meeting criteria of 
CTCAE v5.0 Grade 3 or greater. 
 
• Any SAE (irrespective of relatedness to study drug). 
• Any adverse dermal findings that, at the discretion of the study team and investigator, 
indicate that dosing should be halted. 
 
• Please refer to Section 7 for additional individual discontinuation criteria. 
6.6. Continued Access to Study Intervention After the End of the Study 
No intervention will be provided to study participants at the end of the study. 
 
6.7. Treatment of Overdose 
For this study, the maximum feasible formulation of IP specified below, Q12H to designated 
surface area within a 24-hour time period ±2 hour will be considered an overdose: 
 
• any dose of PF-07295324 greater than 0.12% within a 24-hour time period ±2 hours 
will be considered an overdose. 
 
• any dose of PF-07259955 greater than 2% within a 24-hour time period ±2 hours will 
be considered an overdose. 
 
There is no specific treatment for an overdose. 
 
In the event of an overdose, the investigator should: 
 
1. Contact the medical monitor within 24 hours. 
 
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF-07295324 and 
PF-07259955 (whichever is longer). 
 
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF. 


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4. Overdose is reportable to Pfizer Safety only when associated with an SAE. 
 
5. Obtain a blood sample for PK analysis within 1 day from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case 
basis). 
 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 
 
6.8. Concomitant Therapy 
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of 
investigational product. Limited use of nonprescription medications that are not believed to 
affect participant safety or the overall results of the study may be permitted on a case-by-case 
basis following approval by the sponsor. Acetaminophen/paracetamol may be used at doses 
of ≤1 g/day. 
 
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 investigational product will be 
documented as a prior treatment. Treatments taken after the first dose of investigational 
product will be documented as concomitant treatments. 
 
6.8.1. Rescue Medicine 
There is no rescue therapy to reverse the AEs observed with PF-07295324 and PF-07259955; 
standard medical supportive care must be provided to manage the AEs. 
 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. Discontinuation of Study Intervention 
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: 
 
• Refused further follow-up; 
• Lost to follow-up; 
• Death; 
• Study terminated by sponsor. 


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Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant will remain in the study to 
be evaluated for safety, tolerability, and skin irritation potential. See the SoA for data to be 
collected at the time of discontinuation of study intervention and follow-up for any further 
evaluations that need to be completed. 
 
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information. 
 
7.1.1. ECG Changes 
A participant who meets either of the bulleted criterion based on the average of triplicate 
ECG readings will be withdrawn from the study. 
 
• QTcF >500 msec. 
• Change from baseline: QTcF >60 msec. 
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE. 
 
See the SoA for data to be collected at the time of intervention discontinuation and follow-up 
and for any further evaluations that need to be completed. 
 
7.1.2. Potential Cases of Acute Kidney Injury 
Abnormal values in SCr concurrent with presence or absence of increase in BUN that meet 
the criteria below, in the absence of other causes of kidney injury, are considered potential 
cases of acute kidney injury and should be considered important medical events. 
 
An increase of ≥0.3 mg/dL (or ≥26.5 µmol/L) in SCr level relative to the participant’s own 
baseline measurement should trigger another assessment of SCr as soon as practically 
feasible, preferably within 48 hours from awareness. 
 
If the second assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 µmol/L] in SCr 
relative to the participant’s own baseline measurement) is ≥0.4 mg/dL (or ≥35.4 µmol/L), the 
participant should be discontinued from the study and adequate, immediate, supportive 
measures taken to correct apparent acute kidney injury. 
 
Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
SCr result. This evaluation should include laboratory tests, detailed history, and physical 


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assessment. In addition to repeating SCr, laboratory tests should include serum BUN, serum 
creatine kinase, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
examination, and urinary indices. All cases confirmed on repeat testing as meeting the 
laboratory criteria for acute kidney injury, with no other cause(s) of laboratory abnormalities 
identified, should be considered potential cases of drug-induced kidney injury irrespective of 
availability of all the results of the investigations performed to determine etiology of the 
abnormal SCr. If ≥2 healthy participants in a given treatment arm are noted to have 
2 consecutive SCr results of ≥0.3 mg/dL (or ≥26.5 µmol/L), an assessment of whether the 
finding may be considered an adverse drug reaction should be undertaken. 
 
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator. Reasons for discontinuation from 
the study include the following: 
 
• Refused further study procedures; 
• Lost to follow-up; 
• Death; 
• Study terminated by sponsor; 
• Behavioral, compliance, or administrative reasons. 
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal. 
 
The participant will be permanently discontinued from the study intervention and the study at 
that time. 
 
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. 
 
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent. 


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When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the Case Report Form (CRF) and reported on the Clinical Trial (CT) SAE Report. 
 
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved. 
 
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law. 
 
Participants who withdraw from the study for non-safety reasons may be replaced at the 
discretion of the investigator upon consultation with the sponsor. 
 
7.3. Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study; 
 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record; 
 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 


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8. STUDY ASSESSMENTS AND PROCEDURES 
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
 
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention. 
 
Participants will be screened within 28 days prior to application of the study intervention to 
confirm that they meet the study population criteria. If the time between screening and 
dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug shipment), then 
participants do not require rescreening if the laboratory results obtained prior to first dose 
administration meet eligibility criteria. 
 
A participant who qualified for this protocol but did not enroll from an earlier cohort/group 
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study. In 
addition, other clinical assessments or specimen collections, eg, banked biospecimens, may 
be used without repeat collection, as appropriate. 
 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention. 
 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
 
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner. 
 
Safety/laboratory/analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded. 


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If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter. 
 
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study. 
 
The total blood sampling volume for individual participants in this study is approximately 
165 mL. The actual collection times of blood sampling may change. Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 60 consecutive 
days. 
 
To prepare for study participation, participants will be instructed on the information in the 
LifeStyle Considerations and Concomitant Therapy sections of the protocol. 
 
8.1. Efficacy Assessments 
Not Applicable. 
 
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues. 
 
8.2.1. Physical Examinations 
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 
 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant-reported symptoms. 
 
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation. 
 
Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 
surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
 
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 


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definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.3.1 to Section 8.3.3. 
 
8.2.2. Vital Signs 
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study. Participants should be 
instructed not to speak during measurements. 
 
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds. When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection. 
 
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data. 
 
8.2.3. Electrocardiograms 
12-Lead ECGs should be collected at times specified in the SoA section of this protocol 
using an ECG machine that automatically calculates the heart rate and measures PR, QT, and 
QTcF intervals and QRS complex. All scheduled ECGs should be performed after the 
participant has rested quietly for at least 10 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 before dose administration on Day 1 will serve as 
each participant’s time-controlled 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 
≥30 msec from the baseline and is >450 msec; or b) an absolute QTcF value is ≥500 msec 
for any scheduled ECG. If either of these conditions occur, 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. 
 
If a postdose QTcF interval remains ≥30 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner, 
at the discretion of the investigator), or QTc intervals get progressively longer, the participant 
should undergo continuous ECG monitoring. A cardiologist should be consulted if QTc 
intervals do not return to less than the criterion listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator). 
 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 


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same positions each time in order to achieve precise ECG recordings. If a machine-read 
QTcF value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range. 
 
ECG values of potential clinical concern are listed in Appendix 7. 
 
8.2.4. Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues. 
 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition. 
 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 36 hours after the last dose of study intervention should 
be repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or 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. 
 
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF. 
 
Participants may undergo random urine drug testing at the discretion of the investigator. 
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
 
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury. 
 
8.2.5. Application Site Assessments 
Local toleration will be assessed as specified in the SoA, by Draize scoring (Table 5) and via 
clinical observation. 


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A clinical research site staff member trained in the evaluation of skin will assess local 
toleration at the treatment test areas by examining the skin under standard light conditions for 
visible skin irritation; findings on this scale do not require reporting as an AE unless the skin 
response is deemed to be clinically significant by the investigator. Unscheduled Draize 
evaluations may be performed at any time during the study as deemed necessary by the 
investigator. 
 
Scores for erythema, edema, papules, and vesicles are judged to be present if they involve 
25% or more of the test area. Identifiable reaction(s) encompassing less than 25% of the test 
areas are to be documented as a comment rather than a score or grade. All numerical, letter 
grades, and superficial observations will be collected on the designated CRF. 
 
The site staff member will be recommended to adequately describe the appearance of the 
skin irritation in addition to the Draize score assessment. 
 
Table 5. 
Skin Irritation Assessment Using Draize Scoring 
 
Definition 
Score 
No reaction visible 
0 
Trace reaction – barely perceptible pinkness 
1 
Mild reaction – readily visible pinkness 
2 
Moderate reaction – definite redness 
3 
Strong to severe reaction – very intense redness 
4 
 
Definition of letter grades appended to a numerical grade: 
 
J 
Burning, stinging, itching 
E 
Edema – swelling, spongy feeling when palpated 
P 
Papules – red, solid, pinpoint elevations, granular feeling 
V 
Vesicles – small elevation containing serous fluid (blister-like), diameter 5 mm or less 
B 
Bulla reaction – fluid-filled lesion greater than 0.5 cm in diameter 
S 
Spreading – evidence of the reaction beyond the test site 
W 
Weeping – result of a vesicular or bulla reaction – serous exudates – clear fluid oozing or 
covering test area 
I 
Induration – solid, elevated, hardened, thickening skin reaction 
XC 
Additional comments appear in Comments section 
 
Definition of superficial observations appended to a numerical and/or letter grade: 
 
G 
Glazing 
Y 
Peeling 
C 
Scab, dried film of serous exudates of vesicular or bulla reaction 
D 
Hyperpigmentation (reddish-brown discoloration of test area) 
H 
Hypopigmentation (loss of visible pigmentation at test area) 
F 
Fissuring – grooves in the superficial layers of the skin to glistening 
R 
Erosion(s) 
U 
Ulceration(s) 
K 
Scaling – flaking of skin 


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Photographs of dosing area are taken to document Draize scoring reaction ≥3 or AE at the 
treatment application site. These photographs are for illustrative reference only and will be 
used to document Draize scores ≥3.Photographs will be taken in a non-identifiable manner 
without participants face in frame. 
 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting. 
The definitions of an AE and an SAE can be found in Appendix 3. 
 
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the Investigator or 
other healthcare providers (clinical signs, test results, etc.). 
 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
 
During the active collection period as described in Section 8.3.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner. 
 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion. 
 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days after the last administration of the study intervention. 
 
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator. 
 
For participants who are screen failures, the active collection period ends when screen failure 
status is determined. 
 
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn. 
 
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form. 


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Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and he/she 
considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the CT SAE Report Form. 
 
8.3.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
 
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF 
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF. 
 
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant. 
 
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4. 
 
8.3.2. Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
 
8.3.3. Follow-Up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). 


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In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
 
Further information on follow-up procedures is given in Appendix 3. 
 
8.3.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators. 
 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
 
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements. 
 
8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure 
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure. 
 
Any such exposure to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness. 
 
8.3.5.1. Exposure During Pregnancy 
An EDP occurs if: 
 
• A female participant is found to be pregnant while receiving or after discontinuing 
study intervention. 
 
• A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception. 


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• A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental EDP: 
 
• A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion or skin contact. 
 
• A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion or skin contact then exposes his female partner prior to 
or around the time of conception. 
 
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
 
• If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 28 days after 
the last dose. 
 
• If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file. 
 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported). 
 
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 
 
• Spontaneous abortion including miscarriage and missed abortion; 


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• Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner. 
 
8.3.5.2. Exposure During Breastfeeding 
An exposure during breastfeeding occurs if: 
 
• A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention. 
 
• A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by ingestion, inhalation, or skin contact. 
 
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file. 
 
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding. 
 
8.3.5.3. Occupational Exposure 
The investigator must report any instance of occupational exposure to Pfizer Safety within 24 
hours of the investigator’s awareness using the CT SAE Report Form regardless of whether 
there is an associated SAE. Since the information about the occupational exposure does not 
pertain to a participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed CT SAE Report Form must be maintained in the 
investigator site file. 


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An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE. 
 
8.3.6. Cardiovascular and Death Events 
Not applicable. 
 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
 
8.3.8. Adverse Events of Special Interest 
Not applicable. 
 
8.3.8.1. Lack of Efficacy 
This section is not applicable because efficacy is not expected in the study population. 
 
8.3.9. Medical Device Deficiencies 
Not applicable. 
 
8.3.10. Medication Errors 
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength. 
 
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors. 
 
Safety Event 
Recorded on the CRF 
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness 
Medication errors 
All (regardless of whether 
associated with an AE) 
Only if associated with an SAE 
 
Medication errors include: 
 
• Medication errors involving participant exposure to the study intervention; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant. 
 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page. 


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In the event of a medication dosing error, the sponsor should be notified within 24 hours. 
 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF. 
 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE. 
 
8.4. Pharmacokinetics 
Blood samples will be collected for measurement of plasma concentrations of PF-07295324 
or PF-07259955 as specified in the SoA. Instructions for the collection and handling of 
biological samples will be provided in the laboratory manual or by the sponsor. The actual 
date and time (24-hour clock time) of each sample will be recorded. 
 
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after application 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. 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. 
 
Samples collected for measurement of plasma concentrations of PF-07295324 or 
PF-07259955 will be analyzed using a validated analytical method in compliance with 
applicable SOPs. 
 
Genetic analyses will not be performed on these plasma samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained. 
 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised. 
 
Drug concentration information that may unblind the study will not be reported to 
investigator sites or blinded personnel until the study has been unblinded. 


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Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/IEC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD. 
 
8.4.1. Pharmacokinetics of PF-07295324 
Blood samples of approximately 4 mL, to provide approximately 1.2 mL of plasma, will be 
collected for analysis of plasma concentrations of PF-07295324 as specified in the SoA. 
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual. The actual date and time (24 hour clock time) of each sample will be 
recorded. 
CCI 
 
8.4.2. Pharmacokinetics for PF-07259955 
Blood samples of approximately 4 mL, to provide approximately 1.2 mL of plasma, will be 
collected for analysis of plasma concentrations of PF-07259955 as specified in the SoA. 
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual. The actual date and time (24 hour clock time) of each sample will be 
recorded. 
CCI 
 
8.5. Genetics 
8.5.1. Specified Genetics 
Genetics (specified analyses) are not evaluated in this study. 
 
8.5.2. Retained Research Samples for Genetics 
A 4-mL blood sample optimized for DNA isolation Prep D1 (dispotassium edetic acid 
[ethylenediaminetetraacetic acd] [K2EDTA] whole-blood collection optimized for DNA 
analysis) will be collected according to the SoA, as local regulations and IRBs/ECs allow. 
 
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 
banked samples. 
 
See Appendix 5 (Section 10.5)for information regarding genetic research. Details on 
processes for collection and shipment of these samples can be found in the lab manual and 
supporting documentation. 


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CCI 


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CCI 
 
8.7. Immunogenicity Assessments 
Immunogenicity assessments are not included in this study. 
 
8.8. Health Economics 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 
 
9. STATISTICAL CONSIDERATIONS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor. The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment. 
 
9.1. Statistical Hypotheses 
No statistical hypotheses will be tested in this study. 
 
9.2. Analysis Sets 
For purposes of analysis, the following analysis sets are defined: 
 
Population 
Description 
Enrolled 
All participants who sign the ICD. 
Randomly assigned to 
investigational product 
All participants who sign the ICD and determined eligible to 
participate in the study. 
Evaluable 
The evaluable population is defined as all participants who are 
randomly assigned to IP and who are applied at least 1 dose of 
IP. 
Safety 
All participants randomly assigned to IP and who are applied at 
least 1 dose of IP. Participants will be analyzed according to 
the product they actually received. 
PK concentration 
All participants randomly assigned to investigational product 
who received a application of PF-07295324 or PF-07259955 
and in whom at least 1 plasma sample concentration value is 
reported. 
PK parameter 
All participants randomly assigned to investigational product 
who received an application of PF-07295324 or PF-07259955 


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Population 
Description 
and who 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. Efficacy Analyses 
An efficacy analysis is not applicable to this study. 
 
9.3.2. Safety Analyses 
All safety analyses will be performed on the safety population. 
 
AEs, ECGs, BP, pulse rate, skin irritation assessment, and safety laboratory data will be 
reviewed and summarized on an ongoing basis during the study, to evaluate the safety of 
participants. Any clinical laboratory, ECG, BP, and pulse rate abnormalities of potential 
clinical concern will be described. Safety data will be presented in tabular and/or graphical 
format and summarized descriptively, where appropriate. 
 
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered as source data and will 
not be required to be reported, unless otherwise noted. However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE. 
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted. Demographic data collected at screening will be reported. 
 
9.3.2.1. Electrocardiogram Analyses 
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time. 
 
The number (%) of participants with maximum postdose QTc values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
 
Safety QTc Assessment 
 
Degree of 
Prolongation 
Mild (msec) 
Moderate (msec) 
Severe (msec) 
Absolute value 
>450-480 
>480-500 
>500 
Increase from baseline 
30-60 
>60 


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In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized. 
 
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 QTc value 
>500 msec, but the mean of the triplicates is not >500 msec, the data from the participant’s 
individual tracing will be described in a safety section of the clinical study report (CSR) in 
order to place the >500-msec value in appropriate clinical context. However, values from 
individual tracings within triplicate measurements that are >500 msec will not be included in 
the categorical analysis unless the average from the triplicate measurements is also 
>500 msec. Changes from baseline will be defined as the change between the postdose QTc 
value and the average of the time-matched baseline triplicate values on Day -1, or the 
average of the predose triplicate values on Day 1. 
 
9.3.3. Pharmacokinetic Analyses 
9.3.3.1. Derivation of Pharmacokinetic Parameters 
Actual PK sampling times will be used in the derivation of PK parameters. 
 
PK parameters for PF-07295324 and PF-07259955, following topical administration, will be 
derived from the plasma concentration-time profiles using non-compartmental methods, as 
data permit. 
 
The PK parameters to be assessed in this study, their definition, and method of determination 
are listed in Table 6. Actual PK sampling times will be used in the derivation of PK 
parameters. 


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Table 6. 
Plasma PK Parameters* 
 
Parameter 
Day 
Definition 
Method of Determination 
Cmax 
1, 10 
Maximum plasma concentration 
Observed directly from data 
Tmax 
1, 10 
Time at which maximum plasma 
concentration occurs 
Observed directly from data 
Cavg 
1, 10 
Average plasma concentration 
AUCtau/tau; where tau is the 
dosing interval and AUCtau is 
area under the plasma 
concentration-time profile from 
time zero to time tau (), the 
dosing interval 
Ctrough 
1, 5, 7 and 10 
Pre-dose Concentration 
Observed directly from data 
t½ 
10 
Terminal half-life 
Loge(2)/kel, where kel is the 
terminal phase rate constant 
calculated by a linear regression 
of the log-linear 
concentration-time curve 
AUCtau 
1, 10 
Area under the plasma 
concentration-time profile from 
time zero to time tau (), the dosing 
interval 
Linear/Log trapezoidal method 
up to tau, the dosing interval 
CL/F 
10 
Apparent clearance 
Dose/AUCtau 
Vz/F 
10 
Apparent volume of distribution 
Dose/(AUCtau × kel) 
Rac (Cmax) 
10 
Accumulation ratio for Cmax 
Cmax, Day 10/Cmax, (first dose) 
Rac (AUCtau) 
10 
Accumulation ratio for AUCtau 
AUCtau, Day 10/AUCtau, (first dose) 
*as data permits 
 
9.3.3.2. Statistical Methods for PK Data 
No formal inferential statistics will be applied to the PK data. 
 
The plasma concentration of PF-07295324 and PF-07259955 will be listed and descriptively 
summarized, by nominal PK sampling time and by treatment group. Individual participant, 
mean and median profiles of the plasma concentration-time data of PF-07295324 and PF- 
07259955 will be plotted by treatment group using actual (for individual) and nominal (for 
mean and median) times, respectively. Mean and median profiles of PF-07295324 and PF- 
07259955 will be presented separately, on both linear and log scales. 
 
The plasma PK parameters of PF07295324 and PF-07259955 listed in Table 6 above, will be 
summarized descriptively by treatment group in accordance with Pfizer data standards, as 
data permit. Additional PK analyses may be performed if deemed appropriate, and will not 
be included in the CSR. 


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CCI 
 
9.4. Interim Analyses 
No formal interim analysis will be conducted for this study. As this is an 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 dosing decisions for optional cohorts, and/or 
supporting clinical development. 
 
9.5. Sample Size Determination 
The study consists of 2 planned cohorts and a total of approximately 12 participants in these 
planned cohorts. For this FIH study, a sample size of up to approximately 6 participants per 
cohort has been chosen based on the need to minimize first exposure of PF-07295324 and 
PF-07259955 to humans and the requirement to provide adequate safety and tolerability 
assessment at maximum feasible dose level. This sample size has been judged sufficient to 
obtain a preliminary evaluation of safety, tolerability and PK of PF-07295324 and PF- 
07259955, in healthy participants. 
 
In addition, 2 optional cohorts of approximately 6 healthy participants/cohort may be 
included. 


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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
 
• Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines; 
 
• Applicable ICH GCP guidelines; 
• Applicable laws and regulations, including applicable privacy laws. 
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated. 
 
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
 
The investigator will be responsible for the following: 
 
• Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC; 
 
• Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures; 
 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local 
regulations. 
 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 


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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of. 
 
10.1.2. Financial Disclosure 
Not Applicable. 
 
10.1.3. Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant and answer all questions regarding the study. The 
participant should be given sufficient time and opportunity to ask questions and to decide 
whether or not to participate in the trial. 
 
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center. 
 
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities. 
 
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data. 
 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD. 
 
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study. 
 
A copy of the ICD(s) must be provided to the participant. 


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10.1.4. Data Protection 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data. 
 
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password-protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law. 
 
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws. 
 
10.1.5. Committees Structure 
10.1.5.1. Data Monitoring Committee 
This study will not use a DMC. 
 
10.1.6. Dissemination of Clinical Study Data 
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs. 
 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted. 
 
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. 


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EudraCT 
 
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements. 
 
www.pfizer.com 
 
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov. 
 
Documents within marketing authorization packages/submissions 
 
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015. 
 
Data sharing 
 
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted. 
 
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes. 
 
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. 


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The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties. 
 
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process. 
 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality, such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 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 
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. 


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Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
 
Definition of what constitutes source data can be found in the Source Document Locator, 
which is maintained by the sponsor’s designee (Pfizer Clinical Research Unit). 
 
Description of the use of the computerized system is documented in the Source Document 
Locator, which is maintained by the sponsor’s designee (Pfizer Clinical Research Unit). 
 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements. 
 
10.1.9. Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
 
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date. 
 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study -site closure visit has been performed. 
 
The investigator may initiate study -site closure at any time upon notification to the CRO if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants. 
 
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to: 
 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or the ICH GCP 
guidelines; 
 
• Inadequate recruitment of participants by the investigator; 
• Discontinuation of further study intervention development. 


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If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
 
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights. 
 
10.1.10. Publication Policy 
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
 
The investigator agrees to refer to the primary publication in any subsequent publications, 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer -intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results. 
 
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors. 
 
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
 
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply. 
 
10.1.11. Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the CTMS. 
 
To facilitate access to appropriately qualified medical personnel for study related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 


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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 investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. 


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10.2. Appendix 2: Clinical Laboratory Tests 
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory; or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety concerns. 
 
Table 7. 
Protocol Required Safety Laboratory Assessments 
 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
Hematocrit 
RBC count 
MCV 
MCH 
MCHC 
Platelet count 
WBC count 
Total neutrophils 
(Abs) 
Eosinophils (Abs) 
Monocytes (Abs) 
Basophils (Abs) 
Lymphocytes (Abs) 
Reticulocytes (Abs) 
BUN/urea and 
creatinine 
Glucose (fasting) 
Calcium 
Sodium 
Potassium 
Chloride 
Total CO2 (bicarbonate) 
AST, ALT 
Total bilirubin 
Alkaline phosphatase 
Uric acid 
Albumin 
Total protein 
pH 
Glucose (qual) 
Protein (qual) 
Blood (qual) 
Ketones 
Nitrites 
Leukocyte esterase 
Urobilinogen 
Urine bilirubin 
Microscopya 
• COVID-19 testing 
• Urine drug screeningb 
At screening only: 
• FSHc 
• Hepatitis B surface antigen 
• Hepatitis B core antibody 
• Hepatitis C antibody 
• TB testing 
• Human immunodeficiency 
virus 
a. 
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase. 
b. The minimum requirement for drug screening includes cocaine, tetrahydrocannabinol (THC), 
opiates/opioids, benzodiazepines, and amphetamines (others are site and study specific). 
c. 
For confirmation of postmenopausal status only. 
 
 
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. 
 
Investigators must document their review of each laboratory safety report. 
 
Laboratory/analyte results that could unblind the study will not be reported to investigator 
sites or other blinded personnel until the study has been unblinded. 
 
Any remaining serum/plasma from samples collected for clinical safety laboratory 
measurements at baseline and at all times after dose application may be retained and stored 
for the duration of the study. CCI 
 
CCI 
 


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


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


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d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e.  Is a congenital anomaly/birth defect 
f. Is a suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious. 
The event may be suspected from clinical symptoms or laboratory findings 
indicating an infection in a participant exposed to a Pfizer product. The terms 
“suspected transmission” and “transmission” are considered synonymous. These 
cases are considered unexpected and handled as serious expedited cases by 
pharmacovigilance personnel. Such cases are also considered for reporting as 
product defects, if appropriate. 
g. Other situations: 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations, such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
• 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period 
 
AE and SAE Recording/Reporting 
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the CT SAE Report Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the study intervention under study during 
pregnancy or breastfeeding, and occupational exposure. 


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It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF. When the same data are collected, the forms must 
be completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information. 
* 
EDP (with or without an associated AE or SAE): any pregnancy information is reported to 
Pfizer Safety using CT SAE Report Form and EDP Supplemental Form; if the EDP is 
associated with an SAE, then the SAE is reported to Pfizer Safety using the CT SAE 
Report Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form which would also include 
details of any SAE that might be associated with the EDB. 
*** Environmental or Occupational exposure: AEs or SAEs associated with occupational 
exposure are reported to Pfizer Safety using the CT SAE Report Form. 
• 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. 
Safety Event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours 
of Awareness 
SAE 
All 
All 
Nonserious AE 
All 
None 
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding 
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding 
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)* 
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF. 
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE). ** 
Environmental or 
None. Exposure to a study 
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.*** 
occupational exposure 
non-participant is not 
to the product under 
collected on the CRF. 
study to a non- 
participant (not 
involving EDP or EDB). 


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• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE or SAE CRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE or SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
• Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• Moderate: Minimal, local or noninvasive intervention indicated; limiting age- 
appropriate instrumental ADL. Instrumental ADL refers to preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc. 
• Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting 
self care ADL. Self care ADL refers to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden. 
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE or SAE. The investigator will use clinical 
judgment to determine the relationship. 
• A “reasonable possibility” of a relationship conveys that there are facts, 
evidence, and/or arguments to suggest a causal relationship, rather than a 
relationship cannot be ruled out. 


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• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
• The investigator will also consult the IB and/or product information, for 
marketed products, in his/her assessment. 
• For each AE or SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE or SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the 
sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
• If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for 
reporting purposes, as defined by the sponsor. In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator 
must record this causal relationship in the source documents and CRF, and report 
such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements. 
 
 
Follow-Up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations, as medically indicated or as 
requested by the sponsor, to elucidate the nature and/or causality of the AE or 
SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other 
healthcare providers. 
• If a participant dies during participation in the study or during a recognized 
follow--up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology. 


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• New or updated information will be recorded in the originally submitted 
documents. 
• The investigator will submit any updated SAE data to the sponsor within 24 
hours of receipt of the information. 
 
10.3.4. Reporting of SAEs 
 
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as the data 
become available. 
• After the study is completed at a given site, the electronic data collection tool 
will be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection 
tool has been taken off-line, then the site can report this information on a paper 
SAE form (see next section) or to Pfizer Safety by telephone. 
 
 
SAE Reporting to Pfizer Safety via CT SAE Report Form 
• Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety. 
• In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated 
reporting time frames. 


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10.4. Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria 
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 90 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 or homosexual 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 when engaging in any activity that allows for 
passage of ejaculate to another person. 
 
• Male participants should 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. 
 
10.4.2. Female Participant Reproductive Inclusion Criteria 
A female participant is eligible to participate if she is not pregnant or breastfeeding, and the 
following condition applies: 
 
• Is not a WOCBP. 
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
 
10.4.3. Contraception Methods 
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials. 
 
Highly Effective Methods That Have Low User Dependency 
 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation. 
 
2. Intrauterine device. 


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3. Intrauterine hormone-releasing system. 
 
4. Bilateral tubal occlusion (eg, bilateral tubal ligation). 
 
5. Vasectomized partner. 
 
• A vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days. 
 
Highly Effective Methods That Are User Dependent 
 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation. 
 
• Oral; 
• Intravaginal; 
• Transdermal; 
7. Progestogen-only hormone contraception associated with inhibition of ovulation. 
 
• Oral; 
• Injectable. 
8. Sexual abstinence. 
 
• Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant. 


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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 multi-study 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 and 
Study Intervention Rechallenge Guidelines 
Potential Cases of Drug-Induced Liver Injury 
 
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.” 
 
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks. The increase in TBili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be elevated within 
the same laboratory sample). In rare instances, by the time TBili elevations are detected, 
AST/ALT values might have decreased. This occurrence is still regarded as a potential DILI. 
Therefore, abnormal elevations in either AST OR ALT in addition to TBili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases 
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded. 
 
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values: 
 
• Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available. 
 
• For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline: 
 
• Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller). 
 
• Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller). 


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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
 
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
 
In addition to repeating measurements of AST and ALT and TBili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities. 
 
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology 


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


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• Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm 
(heart rate <40 bpm), accelerated idioventricular rhythm (HR >40 bpm to 
<100 bpm), and monomorphic/polymorphic ventricular tachycardia (HR 
>100 bpm (such as torsades de pointes)). 
• Type II second -degree (Mobitz II) AV block. 
• Complete (third -degree) heart block. 
ECG Findings That Qualify as SAEs 
• Change in pattern suggestive of new myocardial infarction. 
• Sustained ventricular tachyarrhythmias (>30 seconds’ duration). 
• Second- or third -degree AV block requiring pacemaker placement. 
• Asystolic pauses requiring pacemaker placement. 
• Atrial flutter or fibrillation with rapid ventricular response requiring 
cardioversion. 
• Ventricular fibrillation/flutter. 
• At the discretion of the investigator, any arrhythmia classified as an adverse 
experience. 
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs. 


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10.8. Appendix 8: Alternative Measures During Public Emergencies 
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally and will become effective for other public emergencies 
only upon written notification from Pfizer. 
 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
 
10.8.1. Eligibility 
Not applicable. 
 
10.8.2. Telehealth Visits 
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of 
Activities or unscheduled visits. Telehealth visits may be used to continue to assess 
participant safety and collect data points. Telehealth includes the exchange of healthcare 
information and services via telecommunication technologies (e.g., audio, video, video- 
conferencing software) remotely, allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit: 
 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.3. 
• Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 
 
• Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4 and Section 10.8.3.1 of this appendix regarding 
pregnancy tests. 
 
Study participants must be reminded to promptly notify site staff about any change in their 
health status. 
 
10.8.3. Alternative Facilities for Safety Assessments 
10.8.3.1. Laboratory Testing 
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local 
regulations. The local laboratory may be a standalone institution or within a hospital. The 
following safety laboratory evaluations may be performed at a local laboratory: 
 
• See Table 7 


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If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and certifications/ 
accreditations for filing at the site. Laboratory test results are to be provided to the site staff 
as soon as possible. The local laboratory reports should be filed in the participant’s source 
documents/medical records. Relevant data from the local laboratory report should 
be recorded on the CRF. 
 
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 mIU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol. 
 
10.8.3.2. Imaging 
Not applicable. 
 
10.8.3.3. Electrocardiograms 
If the participant is unable to visit the study site for ECGs, the participant may visit an 
alternative facility to have the ECGs performed. Qualified study site personnel must order, 
receive, and review results. 
 
10.8.4. Study Intervention 
If the safety of a trial participant is at risk because they cannot complete required evaluations 
or adhere to critical mitigation steps, then discontinuing that participant from study 
intervention must be considered. 
 
10.8.5. Home Health Visits 
Not applicable 
 
10.8.6. Adverse Events and Serious Adverse Events 
If a participant has COVID-19 during the study, this should be reported as an AE or SAE and 
appropriate medical intervention provided. Discontinuation of the study intervention may be 
medically appropriate until the participant has recovered from COVID-19. 
 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
 
10.8.7. Efficacy Assessments 
Not applicable. 
 
10.8.8. Independent Oversight Committees 
Not applicable. 


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10.9. Appendix 9: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
Abs 
absolute 
AD 
atopic dermatitis 
ADL 
activities of daily living 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUC24 
area under the plasma concentration-time curve from 0 to 24 hours 
AUCtau 
Area under the plasma concentration-time profile from time zero to 
time tau (), the dosing interval 
AV 
atrioventricular 
BBS 
Biospecimen Banking System 
BID 
twice daily 
BMI 
body mass index 
BP 
blood pressure 
bpm 
beats per minute 
BSA 
body surface area 
BUN 
blood urea nitrogen 
BW 
body weight 
Cav/Cavg 
average concentration 
Ctrough 
pre-dose Concentration 
CCL26 
chemokine (C-C motif) ligand 26 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CLp 
clearance of the drug from plasma 
CL/F 
apparent clearance 
Cmax 
maximum observed concentration 
CO2 
carbon dioxide (bicarbonate) 
Coh 
cohort 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRO 
contract research organization 
CRU 
clinical research unit 
CSR 
clinical study report 
CTMS 
clinical trial management system 
CXCL10 
C-X-C motif chemokine 10 
CYP 
cytochrome P450 


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Abbreviation 
Term 
DCT 
data collection tool 
DDI 
drug-drug interaction 
DILI 
Drug -induced liver injury 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
EC 
ethics committee 
ECC 
emergency contact card 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDB 
exposure during breastfeeding 
EDP 
exposure during pregnancy 
EMA 
European Medicines Agency 
EOS 
end of study 
EPO 
erythropoietin 
ET 
early termination 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
Fa 
fraction of drug absorbed 
Fg 
fraction of drug extracted at intestine 
FIH 
first-in-human 
fm 
fraction metabolized 
FSH 
Follicle -stimulating hormone 
Fu,p 
Fraction Unbound in plasma 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practice 
GM-CSF 
granulocyte/macrophage colony stimulating factor 
HBcAb 
hepatitis B core antibody 
HCVAb 
hepatitis C antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HIV 
human immunodeficiency virus 
HR 
heart rate 
CCI 
IB 
investigator’s brochure 
IC50 
50% inhibitive concentration 
ICD 
informed consent document 
ICH 
International Council for Harmonisation 
ID 
identity 
IFN 
interferon 
IFN 
interferon alpha 


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Abbreviation 
Term 
IFN/IFNg 
interferon gamma 
IL 
interleukin 
IND 
investigational new drug 
INR 
international normalized ratio 
IP 
investigational product 
CCI 
IP manual 
investigational product manual 
IPAL 
Investigational Product Accountability Log 
IQMP 
integrated quality management plan 
IRB 
institutional review board 
IV 
intravenous 
JAK 
janus kinase 
kel 
terminal phase rate constant 
LBBB 
left bundle branch block 
LFT 
liver function test 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MFD 
maximum feasible dose 
mL 
milliliter 
MMP12 
matrix metallopeptidase 12 
mRNA 
messenger ribonucleic acid 
msec 
millisecond 
N/A 
not applicable 
nM 
nanomolar 
NOAEL 
No -observed -adverse -effect level 
OCT2 
organic cation transporter 2 
SYS 
systemic 
PACL 
Protocol Administrative Change Letter 
PCRU 
Pfizer Clinical Research Unit 
PD 
pharmacodynamic(s) 
CCI 
PI 
principle investigator 
PK 
pharmacokinetic(s) 
PT 
prothrombin time 
PVC 
premature ventricular contraction/complex 
Q12H 
every 12 hours 
QD 
once daily 
QTc 
corrected QT 
QTcF 
corrected QT (Fridericia method) 
qual 
qualitative 


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Abbreviation 
Term 
Rac (Cmax) 
Accumulation ratio for Cmax 
Rac (AUCtau) 
Accumulation ratio for AUCtau 
RBC 
red blood cell 
CCI 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCr 
serum creatinine 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SRSD 
single reference safety document 
STAT 
signal transducer and activator of transcription 
SUSAR 
suspected unexpected serious adverse reaction 
t½ 
apparent terminal half-life 
Tmax 
time to first occurrence of Cmax 
TB 
tuberculosis 
TBili 
total bilirubin 
TDD 
total daily dose 
Th 
T helper cell 
THC 
tetrahydrocannabinol 
TSLP 
thymic stromal lymphopoietin 
TYK 
tyrosine kinase 
uCavg 
Unbound average concentration 
UGT 
uridine diphosphate-glucuronosyltransferase 
ULN 
upper limit of normal 
US 
United States 
Vd 
Volume of distribution 
Vss 
volume of distribution at steady state 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
WOCBP 
woman/women of childbearing potential 
WONCBP 
woman/women of non-childbearing potential 


PF-07295324 and PF-07259955 
Protocol C4711001 
Final Protocol Amendment 1, 21 April 2022 
PFIZER CONFIDENTIAL 
Page 99 
 
 
 
11. REFERENCES 
 
 
1 
Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol. 
2007;178(5):2623-9. 
 
2 
O’Sullivan LA, Liongue C, Lewis RS, et al. Cytokine receptor signaling through the 
Jak-Stat-Socs pathway in disease. Mol Immunol. 2007;44(10):2497-506. 
 
3 
Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic 
dermatitis and psoriasis--part II: immune cell subsets and therapeutic concepts. J Allergy 
Clin Immunol. 2011;127(6):1420-32. 
 
4 
Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and 
its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 
2017;139(4S):S65-S76. 
 
5 
Peeva E, Hodge MR, Kieras E, et al. Evaluation of a Janus kinase 1 inhibitor, PF- 
04965842, in healthy subjects: A phase 1, randomized, placebo-controlled, dose- 
escalation study. British Journal of Clinical Pharmacology. 2018: 84(8); 1776-78. 
 
6 
Banfield C, Scaramozza M, Zhang W, et al. The safety, tolerability, pharmacokinetics, 
and pharmacodynamics of a TYK2/JAK1 inhibitor (PF-6700841) in healthy subjects 
and patients with plaque psoriasis The Journal of Clinical Pharmacology. 2018 
Apr;58(4):434-447. 

SAP_001.pdf: 
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Protocol C4711001
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, 
VEHICLE-CONTROLLED, FIRST-IN-HUMAN, MULTIPLE-DOSE STUDY, TO 
INVESTIGATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS, OF 
TOPICALLY ADMINISTERED PF-07295324 AND PF-07259955, IN HEALTHY 
ADULT PARTICIPANTS
Statistical Analysis Plan 
(SAP)
Version:
1
Date:
03 Feb 2022


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................3
LIST OF FIGURES ...................................................................................................................3
APPENDICES ...........................................................................................................................3
1. VERSION HISTORY............................................................................................................4
2. INTRODUCTION .................................................................................................................4
2.1. Study Objectives, Endpoints, and Estimands............................................................5
2.2. Study Design .............................................................................................................5
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................6
3.1. Primary Endpoint(s): Safety Endpoints.....................................................................6
3.1.1. Adverse Events .............................................................................................7
3.1.2. Laboratory Data............................................................................................7
3.1.3. Vital Signs ....................................................................................................7
3.1.4. ECG ..............................................................................................................8
3.2. Secondary Endpoint(s): PK Parameters ....................................................................8
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS).....................................................9
4.1. Treatment Misallocations........................................................................................10
4.2. Protocol Deviations.................................................................................................10
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................10
5.1. Hypotheses and Decision Rules ..............................................................................10
5.2. General Methods .....................................................................................................10
5.2.1. Analyses for Continuous Endpoints ...........................................................11
5.2.2. Analyses for Categorical Endpoints ...........................................................11
5.3. Methods to Manage Missing Data ..........................................................................11
6. ANALYSES AND SUMMARIES ......................................................................................12
6.1. Primary Endpoint(s) ................................................................................................12
6.1.1. Safety Summaries and Analyses.................................................................12
6.1.1.1. Adverse Events..........................................................................12
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6.1.1.2. Laboratory Data.........................................................................12
6.1.1.3. Vital Signs.................................................................................13
6.1.1.4. ECG...........................................................................................13
6.2. Secondary Endpoint(s) ............................................................................................14
6.2.1. PK Parameters ............................................................................................14
6.4. Subset Analyses.......................................................................................................16
6.5. Baseline and Other Summaries and Analyses.........................................................16
6.5.1. Baseline Summaries....................................................................................16
6.5.2. Study Conduct and Participant Disposition................................................16
6.5.3. Concomitant Medications and Nondrug Treatments..................................16
7. INTERIM ANALYSES.......................................................................................................16
7.1. Introduction .............................................................................................................16
7.2. Interim Analyses and Summaries............................................................................16
8. APPENDICES .....................................................................................................................17
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................4
Table 2.
Plasma PK Parameters................................................................................9
Table 3.
PK Parameters to be Summarized Descriptively......................................14
LIST OF FIGURES
Figure 1.
Study Schema .............................................................................................6
APPENDICES
Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern .....17
Appendix 2. List of Abbreviations...........................................................................................18
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1. VERSION HISTORY
Table 1.
Summary of Changes
Version/
Date
Associated
Protocol 
Amendment
Rationale
Specific Changes
1
03 Feb 2022
Original 
06 Dec 2021
N/A
N/A
2. INTRODUCTION
PF-07295324 and PF-07259955 are JAK inhibitors, and are proposed for topical treatment 
of mild to moderate AD. 
The purpose of the study is to evaluate the safety, local and systemic tolerability, and 
pharmacokinetics following multiple doses of topically applied, maximum feasible 
formulation of PF-07295324 (0.12% w/w) and PF-07259955 (2% w/w), on approximately 
20% BSA in healthy adult participants.  
As is typical for first-in-human (FIH) studies, the population envisioned for this study will be 
healthy, adult, male and female participants.  Female participants will be confirmed to be 
categorized as women of non-childbearing potential (WONCBP) as, at the present time, 
embryo fetal developmental toxicology studies with PF-07295324 and PF-07259955 have 
not been conducted.  In male participants, appropriate measures to minimize potential 
transfer of PF-07295324 and PF-07259955 via semen to partners are expected to be 
followed (refer to Section 10.4).
As this is the first time PF-07295324 and PF-07259955 will be topically administered in 
humans, safety risks to participants will be minimized by conducting the study in in-patient 
settings, with adequate monitoring of local and systemic AEs, safety laboratory parameters, 
12-lead ECGs, and vital signs. Cumulative safety data will be reviewed after the completion 
of each cohort. 
The safety, local and systemic tolerability, and PK from this study will support the parallel 
clinical development of PF-07295324 and PF-07259955.
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C4711001.  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.


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2.1. Study Objectives, Endpoints, and Estimands
Objectives
Endpoints
Primary: 
Primary:

To evaluate the safety, and local and systemic 
tolerability, of PF-07295324 and 
PF-07259955, following multiple doses 
of topically administered PF-07295324 or 
PF-07259955, on approximately 20% BSA in 
healthy adult participants.

Incidence and severity of systemic AEs, safety 
laboratory tests, vital signs (including blood 
pressure and pulse rate), and heart rhythms as 
assessed via 12-lead electrocardiogram (ECG).

Incidence and severity of application site AEs as 
assessed by Draize score.
Secondary: 
Secondary:

To characterize plasma PK following multiple 
topical applications of PF-07295324 and 
PF-07259955.

Plasma PK of multiple topical doses of 
PF-07295324 and PF-07259955, as data 
permits:
Day 1: Cmax, Tmax, Cavg, Ctrough, AUCtau
Day 10: Cmax, Tmax, Cavg, Ctrough, AUCtau, Rac
(Cmax), Rac(AUCtau), t½, CL/F, and Vz/F
 
 
 
2.2. Study Design
C4711001 is an investigator- and participant-blinded, interventional, randomized, 
vehicle-controlled, Phase 1 study to evaluate the safety, and local and systemic tolerability 
and pharmacokinetics of maximum feasible formulation of topical JAK inhibitors, 
PF-07295324 (0.12%) and PF-07259955 (2%) in healthy adult participants.  
This study will enroll healthy adult participants in ≤4 cohorts: 2 planned cohorts and 
2 optional cohorts. Approximately 6 participants will be enrolled in each cohort, 
randomized as 4 active:2 vehicle. Cohort 1 and the optional Cohort 3 will be assigned to 
PF-07295324/vehicle, administered topically as an ointment. Cohort 2 and the optional 
Cohort 4 will be assigned to PF-07259955/vehicle administered topically as a cream.
Participants will be enrolled in the optional cohorts in a sequential design to the respective 
planned cohort, as shown in Figure 1. Planned cohorts assigned to different interventions 
may progress simultaneously. Similarly, optional cohorts assigned to different interventions 
may progress simultaneously (Figure 1).  
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Up to 2 optional cohorts (Cohort 3 and Cohort 4) of up to 6 participants/cohort may be 
enrolled in this study. Participants enrolled in the optional cohort will be randomized to 
either active or vehicle (4:2). The optional cohorts may be used to explore lower strength 
formulations on approximately 20% BSA, or to repeat the maximum feasible formulation on 
lower body surface area, or to administer maximum feasible formulation at a less frequent 
dosing regimen on approximately 20% BSA. Participants enrolled in the optional cohorts 
will be guided by the same stopping criteria as the planned cohorts.
Figure 1.
Study Schema
a. PF-07295324 (0.12%)/vehicle in Cohort 1 or PF-07259955 (2%)/vehicle in Cohort 2, will be topically 
applied on approximately 20% body surface area, Q12H from D1 to D9; only morning (AM) dose will 
be applied on D10.
b. Based on review of emerging safety from Cohort 1, optional Cohort 3 may be enrolled to explore lower 
formulation strength of PF-07295324, topically applied on approximately 20% BSA or PF-07295324 
(0.12%) on lower body surface area or at a less frequent dosing regimen on approximately 20% BSA.
c. Based on review of emerging safety assessments from Cohort 2, optional Cohort 4 may be enrolled to explore
lower formulation strength of PF-07259955 topically applied on approximately 20% BSA or PF-07259955 
(2%) on lower body surface area or at a less frequent dosing regimen on approximately 20% BSA.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s): Safety Endpoints

Incidence and severity of systemic AEs, safety laboratory tests, vital signs (including 
blood pressure and pulse rate), and heart rhythms as assessed via 12-lead 
electrocardiogram (ECG). 

Incidence and severity of application site AEs as assessed by Draize score.


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The following data are considered in standard safety summaries (see protocol for collection 
days, baseline assessment, and list of parameters):

AEs;

Safety laboratory tests;

Vital signs (Blood Pressure and Pulse rate);

ECG.
3.1.1. Adverse Events
An adverse event (AE) is considered a Treatment-Emergent Adverse Event (TEAE) if the 
event started during the effective duration of treatment. All events that start on or after the 
first dosing day and time/start time, if collected, but before the last dose plus the lag time, 
will be flagged as TEAEs. The lag time is defined by the Pfizer Standard of 365 days post 
last dose. The algorithm will not consider any events that started prior to the first dose date. 
If an AE starts on the same day as the first dose date, it will be considered treatment 
emergent unless the CRF data indicates otherwise via explicitly recording time for AE onset 
which was occurred before the first treatment dosing.
Local toleration of skin irritation assessment will be assessed as specified in the Schedule of 
Activities (SoA) given in the protocol, by Draize scoring and via clinical observation (see
Section 8.2.5 in the protocol). 
3.1.2. Laboratory Data
Safety laboratory tests will be performed as described in the protocol. See Protocol 
Appendix 2 for the list of clinical safety laboratory tests to be performed.
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 not take into 
account whether each subject’s baseline test result is within or outside the laboratory 
reference range for the particular laboratory parameter. 
Baseline of safety laboratory tests is defined as the pre-dose measurement on Day -1. If a 
value is missing on Day -1, then the last pre-dose measurement will be used as baseline.
3.1.3. Vital Signs
Supine blood pressure and pulse rate measurements will be taken at all time points listed in 
the SoA given in the protocol. 


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The baseline measurement is the pre-dose measurement at Hour 0 taken on Day 1. If a value 
is missing on Day 1, then the last pre-dose measurement will be used as baseline. 
3.1.4. ECG
Triplicate 12-lead ECGs will be obtained approximately 2 to 4 minutes apart; the average of 
the triplicate ECG measurements collected before dose administration on Day 1 will serve as 
each participant’s time-controlled baseline QTcF value. If a value is missing on Day 1, then 
the last pre-dose measurement will be used as baseline.
The QT, QTc, PR, QRS and heart rate will be recorded at each assessment time. 
If not supplied, QTcF will be derived using Fridericia’s heart rate correction formula: 
QTcF = QT/(RR)1/3  
where RR = 60/HR (if not provided)
3.2. Secondary Endpoint(s): PK Parameters

Plasma PK of multiple topical doses of PF-07295324 and PF-07259955, as data
permits:
Day 1: Cmax, Tmax, Cavg, Ctrough, AUCtau
Day 10: Cmax, Tmax, Cavg, Ctrough, AUCtau, Rac (Cmax), Rac(AUCtau), t½, CL/F, and Vz/F
Actual PK sampling times will be used in the derivation of PK parameters.
PK parameters for PF-07295324 and PF-07259955, following topical administration, will be 
derived from the plasma concentration-time profiles using non-compartmental methods, as 
data permit.  
The PK parameters to be assessed in this study, their definition, and method of determination 
are listed in Table 2. Actual PK sampling times will be used in the derivation of PK 
parameters.


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Table 2.
Plasma PK Parameters
Parameter
Day
Definition
Method of Determination
Cmax
1, 10
Maximum plasma concentration
Observed directly from data
Tmax
1, 10
Time at which maximum plasma 
concentration occurs
Observed directly from data
Cavg
1, 10
Average plasma concentration
AUCtau/tau; where tau is the 
dosing interval and AUCtau is 
area under the plasma 
concentration-time profile from 
time zero to time tau (), the 
dosing interval
Ctrough
1, 5, 7 and 10
Pre-dose Concentration
Observed directly from data
t½a
10
Terminal half-life
Loge(2)/kel, where kel is the 
terminal phase rate constant 
calculated by a linear regression 
of the log-linear 
concentration-time curve
AUCtau
1, 10
Area under the plasma 
concentration-time profile from 
time zero to time tau (), the dosing 
interval
Linear/Log trapezoidal method 
up to tau, the dosing interval
CL/F
10
Apparent clearance
Dose/AUCtau
Vz/Fa
10
Apparent volume of distribution
Dose/(AUCtau × kel)
Rac (Cmax)
10
Accumulation ratio for Cmax
Cmax, Day 10/Cmax, (first dose)
Rac (AUCtau)
10
Accumulation ratio for AUCtau
AUCtau, Day 10/AUCtau, (first dose)
a.  as data permit.
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures.
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Population
Description
Enrolled 
All participants who sign the ICD.
Randomly assigned to 
investigational product
All participants who sign the ICD and determined eligible to 
participate in the study.
Evaluable
The evaluable population is defined as all participants who are 
randomly assigned to IP and who are applied at least 1 dose of IP.
Safety
All participants randomly assigned to IP and who are applied at 
least 1 dose of IP.  Participants will be analyzed according to the 
product they actually received.
PK concentration
All participants randomly assigned to investigational product who 
received an application of PF-07295324 or PF-07259955 and in 
whom at least 1 plasma sample concentration value is reported.
PK parameter 
All participants randomly assigned to investigational product who 
received an application of PF-07295324 or PF-07259955 and who 
have at least 1 of the PK parameters of interest calculated.
4.1. Treatment Misallocations
All analyses will be performed on an “as-treated” basis and will not include data from 
participants who are randomized but not treated.
If a participant takes a treatment that is not consistent with the treatment they are randomized 
to, for example takes a treatment out of sequence or takes the same treatment twice, then they 
will be reported under the treatment that they actually receive for all safety, PK and 
pharmacodynamic analyses, where applicable.
4.2. Protocol Deviations
Participants who experience events that may affect their PK profile may be excluded from 
the PK analysis. At the discretion of the pharmacokineticist, a concentration value may also 
be excluded if the deviation in sampling time is of sufficient concern or if the concentration 
is anomalous for any other reason.
A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure.
5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
No formal hypothesis testing will be performed in this study.
5.2. General Methods
Descriptive analyses will be performed. Some measures will be summarized using graphical 
representations, where appropriate.


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5.2.1. Analyses for Continuous Endpoints
For continuous variables, the data will be summarized using the number of subjects, mean, 
median, standard deviation, minimum, and maximum in accordance with current Pfizer’s 
data and reporting standards. For appropriate PK parameters, geometric mean and geometric 
coefficient of variation (geocv%) will also be summarized.
5.2.2. Analyses for Categorical Endpoints
For categorical or ordinal variables, number of subjects, numbers and percentages of subjects 
meeting the categorical criteria will be supplied in accordance with current Pfizer’s data and 
reporting standards.
5.3. Methods to Manage Missing Data
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.
Methods to handle missing PK data are described below. 
Concentrations Below the Limit of Quantification:
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero. (In listings BLQ values will be reported as “<LLQ” where LLQ 
will be replaced with the value for the lower limit of quantification).
Deviations, Missing Concentrations and Anomalous Values: 
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if 1 of the following cases is true: 
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample), 
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist. 
Note that summary statistics will not be presented at a particular time point if more than 
50% of the data are missing. 
Pharmacokinetic Parameters: 
Actual PK sampling times will be used in the derivation of PK parameters. If a PK parameter 
cannot be derived from a subject’s concentration data, the parameter will be coded as NC 
(ie, not calculated). (Note that NC values will not be generated beyond the day that a subject 
discontinues). In summary tables, statistics will be calculated by setting NC values to 


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missing; and statistics will be presented for a particular dose with ≥3 evaluable 
measurements. 
If an individual subject has a known biased estimate of a PK parameter (due for example to 
an unexpected event such as vomiting before all the compound is adequately absorbed from 
the gastrointestinal tract), this will be footnoted in summary tables and will not be included in 
the calculation of summary statistics or statistical analyses.
6. ANALYSES AND SUMMARIES
6.1. Primary Endpoint(s)
6.1.1. Safety Summaries and Analyses
All safety analyses will be performed on the safety population (See Section 4).
AEs, ECGs, BP, pulse rate, skin irritation assessment, and safety laboratory data will be 
reviewed and summarized on an ongoing basis during the study, to evaluate the safety of 
participants.  Any clinical laboratory, ECG, BP, and pulse rate abnormalities of potential 
clinical concern will be described.  Safety data will be presented in tabular and/or graphical 
format and summarized descriptively, where appropriate.
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered as 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.
PF-07295324 and PF-07259955 will have corresponding vehicle groups throughout, 
ie, vehicle groups will be summarized by administration type (ointment and cream).
6.1.1.1. Adverse Events
Adverse events will be reported in accordance with the sponsor reporting standards.
Subject discontinuations due to adverse events will be detailed by treatment. Data will be 
reported in accordance with sponsor reporting standards.
Skin irritation assessment using Draize Score will be listed and summarized by treatment.
6.1.1.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with the sponsor 
reporting standards. 


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6.1.1.3. Vital Signs
Single supine blood pressure and pulse will be collected at times specified in the SoA in the 
protocol.
The following vital signs endpoints will be determined and summarized for each treatment 
group:

Actual values, change from baseline in supine blood pressure and pulse rate over all 
measurements taken postdose;

The maximum decrease and increase from baseline over all measurements taken 
postdose for supine blood pressure.
The increase from baseline will be calculated by subtracting the baseline value from each 
post-dose measurement to give the change from baseline for each participant. The maximum 
of these values over the duration of dosing will be reported as maximum increase from 
baseline, except where a participant does not show an increase. In such an instance, the 
minimum decrease will be reported.
Similarly, decrease from baseline will be calculated by subtracting each post-dose 
measurement from individual participant’s baseline value. Maximum decrease from baseline 
will be reported as the minimum value of the changes from baseline. In cases where a 
participant does not show a decrease, the minimum increase will be reported.
Maximum absolute values and changes from baseline for vital signs will also be tabulated by 
treatment using categories as defined in Appendix.
6.1.1.4. ECG
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
The maximum absolute value (post-dose) and the maximum increase from baseline for 
QTcF, QT, heart rate, PR and QRS, will be determined over all measurements taken 
post-dose and reported.
The number (%) of participants with maximum postdose QTc values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60


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In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
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 QTc value 
>500 msec, but the mean of the triplicates is not >500 msec, the data from the participant’s 
individual tracing will be described in a safety section of the clinical study report (CSR) in 
order to place the >500-msec value in appropriate clinical context.  However, values from 
individual tracings within triplicate measurements that are >500 msec will not be included in 
the categorical analysis unless the average from the triplicate measurements is also 
>500 msec.  Changes from baseline will be defined as the change between the postdose QTc 
value and the average of the time-matched baseline triplicate values on Day -1, or the 
average of the predose triplicate values on Day 1.
6.2. Secondary Endpoint(s)
6.2.1. PK Parameters
All PK analysis will be performed on the PK analysis set (See Section 4).
The PK parameters detailed in Table 2 will be listed and summarized for participants in the 
PK concentration population (see Section 4). Missing values will be handled as detailed in 
Section 5.3. The PK parameters will be calculated using standard non-compartmental 
methods. Each PK parameter will be summarized by cohort, dose and will include the set of 
summary statistics as specified in the table below.
Table 3.
PK Parameters to be Summarized Descriptively
Parameter
Summary Statistics
AUCtau , Cavg , Cmax , Ctrough,
Rac (Cmax), Rac(AUCtau),
CL/F, Vz/F
N, arithmetic mean, median, cv%, standard deviation, minimum, maximum, 
geometric mean and geometric cv%.
Tmax
N, median, minimum, maximum.
t1/2
N, arithmetic mean, median, cv%, standard deviation, minimum, maximum.
No formal inferential statistics will be applied to the PK data.
The plasma concentration of PF-07295324 and PF-07259955 will be listed and descriptively 
summarized, by nominal PK sampling time and by treatment group.  Individual participant, 
mean and median profiles of the plasma concentration-time data of PF-07295324 and 
PF-07259955 will be plotted by treatment group using actual (for individual) and nominal 
(for mean and median) times, respectively.  Mean and median profiles of PF-07295324 and 
PF-07259955 will be presented separately, on both linear and log scales.


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The plasma PK parameters of PF-07295324 and PF-07259955 listed in Table 2, will be 
summarized descriptively by treatment group and by day, in accordance with Pfizer data 
standards, as data permit.  
Supporting data from the estimation of t½ will be listed by analyte where applicable: 
terminal phase rate constant (kel); goodness of fit statistic from the log-linear regression (r2); 
and the first, last, and number of time points used in the estimation of kel. This data may be 
included in the clinical study report.
Presentations for PF-07295324 and PF-07259955 concentrations will include:

A listing of all concentrations sorted by subject ID, cohort, dose and nominal time 
postdose. The concentration listing will also include the actual times. Deviations 
from the nominal time will be given in a separate listing.

A summary of concentrations by cohort, dose and nominal time postdose, where the 
set of statistics will include n, mean, median, standard deviation, coefficient of 
variation (cv), minimum, maximum and the number of concentrations above the 
lower limit of quantification.

Median concentrations time plots (on both linear and semi-log scales) against 
nominal time postdose by cohort and dose (all treatments on the same plot per scale, 
based on the summary of concentrations by cohort, dose and time postdose).

Mean concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose by cohort and dose (all treatments on the same plot per scale, based on 
the summary of concentrations by cohort, dose and time postdose).

Individual concentration time plots by cohort and dose (on both linear and semi-log 
scales) against actual time postdose (there will be separate spaghetti plots for each 
dose per scale).

Individual concentration time plots by subject (on both linear and semi-log scales) 
against actual time postdose [there will be separate plots for each subject (containing 
all doses) per scale].
For summary statistics, median and mean plots by sampling time, the nominal PK sampling 
time will be used, for individual subject plots by time, the actual PK sampling time will be 
used.
Additional PK analyses may be performed if deemed appropriate.


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6.4. Subset Analyses
No subset analyses are planned. 
6.5. Baseline and Other Summaries and Analyses
6.5.1. Baseline Summaries
Baseline summary of demographic characteristics (height, weight, BMI, age and race) will be 
presented for safety population. Each participant’s gender will be summarized by sex at birth 
for each cohort separately and overall in accordance with the sponsor reporting standards.
6.5.2. Study Conduct and Participant Disposition
Subject discontinuations and temporary discontinuations will be detailed and summarized 
using safety population according to Pfizer standards.
6.5.3. Concomitant Medications and Nondrug Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be reported in the 
listings.
7. INTERIM ANALYSES
No formal interim analysis will be conducted for this study.  As this is an 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 dosing decisions for optional cohorts, and/or 
supporting clinical development. 
7.1. Introduction
Not applicable.
7.2. Interim Analyses and Summaries
Available safety and PK data may be reviewed.
CCI


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8. APPENDICES
Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern
Categories for QTcF
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
Categories for PR and QRS
PR (ms)
max. ≥300 
PR (ms) increase 
from baseline
Baseline >200 and 
max. ≥25% increase
Baseline ≤200 and 
max. ≥50% increase
QRS (ms)
max. ≥140
QRS (ms) increase 
from baseline
≥50% increase
Categories for Vital Signs
Systolic BP (mm Hg)
min. <90
Systolic BP (mm Hg) 
change from baseline
max. decrease ≥30
max. increase ≥30
Diastolic BP (mm Hg)
min. <50
Diastolic BP (mm Hg) 
change from baseline
max. decrease ≥20
max. increase ≥20
Supine pulse rate (bpm)
min. <40
max. >120
Measurements that fulfill these criteria are to be listed in the clinical study report.


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Appendix 2. List of Abbreviations
Abbreviation
Term
Abs
absolute
AD
atopic dermatitis
ADL
activities of daily living
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the curve
AUC24
area under the plasma concentration-time curve from 0 to 24 hours
AUCtau
Area under the plasma concentration-time profile from time zero to 
time tau (), the dosing interval
AV
atrioventricular
BBS
Biospecimen Banking System
BID
twice daily
BLQ
below the limit of quantification
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BSA
body surface area
BUN
blood urea nitrogen
BW
body weight
Cav/Cavg
average concentration
Ctrough
pre-dose Concentration
CCL26
chemokine (C-C motif) ligand 26
CFR
Code of Federal Regulations
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLp
clearance of the drug from plasma
CL/F
apparent clearance
Cmax
maximum observed concentration
CO2
carbon dioxide (bicarbonate)
Coh
cohort
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
CXCL10
C-X-C motif chemokine 10
CYP
cytochrome P450


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Abbreviation
Term
DCT
data collection tool
DDI
drug-drug interaction 
DILI
Drug -induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram
eCRF
electronic case report form
EDB
exposure during breastfeeding
EDP
exposure during pregnancy
EMA
European Medicines Agency
EOS
end of study
EPO
erythropoietin
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
Fa
fraction of drug absorbed
Fg
fraction of drug extracted at intestine
FIH
first-in-human
fm
fraction metabolized
FSH
Follicle -stimulating hormone
Fu,p
Fraction Unbound in plasma
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GLP
Good Laboratory Practice
GM-CSF
granulocyte/macrophage colony stimulating factor
HBcAb
hepatitis B core antibody
HCVAb
hepatitis C antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HIV
human immunodeficiency virus
HR
heart rate
IB
investigator’s brochure
IC50
50% inhibitive concentration
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identity
CCI


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Abbreviation
Term
IFN
interferon
IFN
interferon alpha
IFN/IFNg
interferon gamma
IL
interleukin
IND
investigational new drug
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IQMP
integrated quality management plan
IRB
institutional review board
IV
intravenous
JAK
janus kinase
kel
terminal phase rate constant
LBBB
left bundle branch block
LFT
liver function test
LLQ
limit of quantification
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MFD
maximum feasible dose
NC
not calculated
ND
not done
NS
no sample
mL
milliliter
MMP12
matrix metallopeptidase 12
mRNA
messenger ribonucleic acid
msec
millisecond
N/A
not applicable
nM
nanomolar
NOAEL
No -observed -adverse -effect level
OCT2
organic cation transporter 2
SYS
systemic
PD
pharmacodynamic(s)
PI
principle investigator
PK
pharmacokinetic(s)
PT
prothrombin time
CCI
CCI


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Abbreviation
Term
PVC
premature ventricular contraction/complex
Q12H
every 12 hours
QD
once daily
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
Rac (Cmax)
Accumulation ratio for Cmax
Rac (AUCtau)
Accumulation ratio for AUCtau
RBC
red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
SCr
serum creatinine
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
STAT
signal transducer and activator of transcription
STOD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
t½
apparent terminal half-life
TEAE
Treatment-Emergent Adverse Event
Tmax
time to first occurrence of Cmax
TB
tuberculosis
TBili
total bilirubin
TDD
total daily dose
Th
T helper cell
THC
tetrahydrocannabinol
TSLP
thymic stromal lymphopoietin
TYK
tyrosine kinase
uCavg
Unbound average concentration
UGT
uridine diphosphate-glucuronosyltransferase
ULN
upper limit of normal
US
United States
Vd
Volume of distribution
Vss
volume of distribution at steady state
Vz/F
apparent volume of distribution
WBC
white blood cell
WOCBP
woman/women of childbearing potential
WONCBP
woman/women of non-childbearing potential
CCI