Clinical trial NCT04863417
Conditions: Healthy
Sponsor: Pfizer
Start date: 2021-06-30; Completion date: 2021-09-09
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the safety, tolerability, skin irritation potential, and PK of PF-07038124 in Japanese healthy adult participants.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: PF-07038124 or vehicle intervention 2: PF-07038124 or vehicle
Intervention descriptions: intervention 1: PF-07038124 0.01% or vehicle Ointment QD applied to 2000 cm2 Body Surface Area intervention 2: PF-07038124 0.01% or vehicle Ointment QD applied to 4000 cm2 Body Surface Area

Protocol documents:
Prot_000.pdf: 
PF-07038124 
Protocol C3941003
Final Protocol Amendment 1, 12 March 2021
PFIZER CONFIDENTIAL
Page 1
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, 
PARALLEL COHORT STUDY TO EVALUATE THE SAFETY, TOLERABILITY, 
SKIN IRRITATION POTENTIAL AND PHARMACOKINETICS OF 
MULTIPLE-DOSE, TOPICAL ADMINISTRATION OF PF-07038124 
TO JAPANESE HEALTHY PARTICIPANTS
Study Intervention Number:
PF-07038124
Study Intervention Name:
N/A
US IND Number:
N/A
EudraCT Number:
N/A
Protocol Number:
C3941003
Phase:
1
Short Title: A Phase 1 Study to Evaluate the Safety, Local and Systemic Tolerability, 
and PK of Multiple-Dose Topical Administration of PF-07038124 in Japanese 
Healthy Participants.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.


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Protocol C3941003
Final Protocol Amendment 1, 12 March 2021
PFIZER CONFIDENTIAL
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Amendment 1
12 March 2021
Added descriptions in Section 6.1.1.3.
Rationale: Addition to define additional 
application sites appropriately to secure 
planned application area.
Added descriptions in Section 8.5.
Rationale: Addition to add an instruction 
of wash around PK sampling to avoid 
contamination.
Added "X" in Section 1.3 Schedule of 
Activities.
Rationale: Addition to be consistent with 
PK sampling schedule.
Revised descriptions in Section 6.5.
Rationale: Revision of the period of 
prior therapy to consistent with Section 
5.2.
Revised descriptions in Section 1.3 
Schedule of Activities, Section 8, 
Section 8.2.2, Section 9.4.6, Section 10.8.
Rationale: Updates to distinguish 
between pulse rate and PR interval.
Revised descriptions in Section 8.8.
Rationale: Updates descriptions 
according to the protocol template 
instruction.
Original protocol
08 January 2021
N/A


PF-07038124 
Protocol C3941003
Final Protocol Amendment 1, 12 March 2021
PFIZER CONFIDENTIAL
Page 3
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
LIST OF FIGURES ...................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................12
1.3. Schedule of Activities .............................................................................................13
2. INTRODUCTION ...............................................................................................................16
2.1. Study Rationale .......................................................................................................16
2.2. Background .............................................................................................................16
2.2.1. Role of Proinflammatory Cytokines in AD and Psoriasis..........................16
2.2.2. Description of Study Intervention: Mechanism of Action .........................17
2.2.3. Preclinical Safety Data ...............................................................................18
2.2.4. Clinical Overview.......................................................................................19
2.2.4.1. Clinical Safety...........................................................................20
2.2.4.2. Clinical Pharmacokinetics.........................................................20
2.3. Benefit/Risk Assessment.........................................................................................21
2.3.1. Risk Assessment.........................................................................................22
2.3.2. Benefit Assessment.....................................................................................23
2.3.3. Overall Benefit/Risk Conclusion................................................................23
3. OBJECTIVES AND ENDPOINTS.....................................................................................23
4. STUDY DESIGN.................................................................................................................23
4.1. Overall Design.........................................................................................................23
4.2. Scientific Rationale for Study Design.....................................................................24
4.3. Justification for Dose ..............................................................................................25
4.4. End of Study Definition ..........................................................................................26
5. STUDY POPULATION......................................................................................................26
5.1. Inclusion Criteria.....................................................................................................27
5.2. Exclusion Criteria....................................................................................................27
5.3. Lifestyle Considerations..........................................................................................30
5.3.1. Meals and Dietary Restrictions...................................................................30


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5.3.2. Caffeine, Alcohol, and Tobacco .................................................................30
5.3.3. Activity .......................................................................................................30
5.3.4. Contraception..............................................................................................31
5.4. Screen Failures ........................................................................................................31
6. STUDY INTERVENTION..................................................................................................31
6.1. Study Intervention(s) Administered........................................................................32
6.1.1. Administration............................................................................................32
6.1.1.1. Study Treatment Regimen.........................................................32
6.1.1.2. Calculation of Per Application Dose.........................................33
6.1.1.3. Application of Study Intervention.............................................33
6.2. Preparation/Handling/Storage/Accountability ........................................................33
6.2.1. Preparation and Dispensing........................................................................34
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................35
6.3.1. Allocation to Study Intervention ................................................................35
6.3.2. Breaking the Blind......................................................................................35
6.4. Study Intervention Compliance...............................................................................35
6.5. Concomitant Therapy..............................................................................................36
6.5.1. Rescue Medicine.........................................................................................36
6.6. Dose Modification...................................................................................................36
6.7. Intervention After the End of the Study..................................................................36
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................36
7.1. Discontinuation of Study Intervention ....................................................................36
7.2. Participant Discontinuation/Withdrawal From the Study.......................................38
7.2.1. Withdrawal of Consent...............................................................................38
7.3. Lost to Follow up ....................................................................................................39
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................39
8.1. Efficacy Assessments..............................................................................................40
8.2. Safety Assessments .................................................................................................41
8.2.1. Physical Examinations................................................................................41
8.2.2. Vital Signs ..................................................................................................41
8.2.2.1. Temperature ..............................................................................41


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Protocol C3941003
Final Protocol Amendment 1, 12 March 2021
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8.2.3. Electrocardiograms.....................................................................................41
8.2.4. Clinical Safety Laboratory Assessments ....................................................42
8.2.5. Skin Irritation Assessment..........................................................................43
8.2.6. Pregnancy Testing ......................................................................................44
8.2.7. COVID-19 Specific Assessments...............................................................44
8.3. Adverse Events and Serious Adverse Events..........................................................45
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......45
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................46
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................46
8.3.2. Method of Detecting AEs and SAEs ..........................................................46
8.3.3. Follow-up of AEs and SAEs.......................................................................46
8.3.4. Regulatory Reporting Requirements for SAEs...........................................46
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................47
8.3.5.1. Exposure During Pregnancy......................................................47
8.3.5.2. Exposure During Breastfeeding ................................................48
8.3.5.3. Occupational Exposure .............................................................49
8.3.6. Cardiovascular and Death Events...............................................................49
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................49
8.3.8. Adverse Events of Special Interest.............................................................49
8.3.8.1. Lack of Efficacy........................................................................49
8.3.9. Medical Device Deficiencies......................................................................50
8.3.10. Medication Errors.....................................................................................50
8.4. Treatment of Overdose............................................................................................50
8.5. Pharmacokinetics ....................................................................................................51
8.6. Pharmacodynamics..................................................................................................52
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8.9. Immunogenicity Assessments.................................................................................53
8.10. Health Economics .................................................................................................53
9. STATISTICAL CONSIDERATIONS ................................................................................53
9.1. Statistical Hypotheses .............................................................................................53
9.2. Sample Size Determination.....................................................................................54
9.3. Analysis Sets ...........................................................................................................54
9.4. Statistical Analyses .................................................................................................54
9.4.1. General Considerations...............................................................................54
9.4.2. Primary Endpoint(s)....................................................................................54
9.4.2.1. Electrocardiogram Analyses......................................................55
9.4.3. Secondary Endpoint(s)................................................................................55
9.4.3.1. Pharmacokinetic Analyses of PF-07038124 .............................55
9.4.6. Other Safety Analyses ................................................................................57
9.5. Interim Analyses .....................................................................................................57
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............57
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................58
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............58
10.1.1. Regulatory and Ethical Considerations ....................................................58
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................58
10.1.2. Financial Disclosure .................................................................................59
10.1.3. Informed Consent Process ........................................................................59
10.1.4. Data Protection .........................................................................................60
10.1.5. Dissemination of Clinical Study Data ......................................................60
10.1.6. Data Quality Assurance ............................................................................61
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10.1.7. Source Documents....................................................................................63
10.1.8. Study and Site Start and Closure ..............................................................63
10.1.9. Publication Policy.....................................................................................64
10.1.10. Sponsor’s Qualified Medical Personnel .................................................64
10.2. Appendix 2: Clinical Laboratory Tests .................................................................66
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................67
10.3.1. Definition of AE .......................................................................................67
10.3.2. Definition of SAE.....................................................................................68
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................69
10.3.4. Reporting of SAEs....................................................................................72
10.4. Appendix 4: Contraceptive Guidance ...................................................................74
10.4.1. Male Participant Reproductive Inclusion Criteria....................................74
10.4.2. Female Participant Reproductive Inclusion Criteria.................................74
10.4.3. Woman of Childbearing Potential ............................................................74
10.4.4. Contraception Methods.............................................................................75
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........78
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................80
10.8. Appendix 8: Abbreviations ...................................................................................82
11. REFERENCES ..................................................................................................................86
LIST OF TABLES
Table 1.
PF-07038124 Clinical Development Program – Completed Studies 
as of January 2021 ....................................................................................19
Table 2.
Descriptive Summary of Day 10 Plasma PF-07038124 PK 
Parameters, C3941001..............................................................................20
Table 3.
Proposed Doses, Predicted Free Exposures, and Safety Margins 
following QD Topical Application of PF-07038124a...............................26
Table 4.
Skin Irritation Assessment Using Draize Scoring ....................................43
Table 5.
Plasma PK Parameters..............................................................................56
Table 6.
Protocol-Required Safety Laboratory Assessments .................................66
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Final Protocol Amendment 1, 12 March 2021
PFIZER CONFIDENTIAL
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LIST OF FIGURES
Figure 1.
Schema of Study C3941003 .....................................................................12


PF-07038124 
Protocol C3941003
Final Protocol Amendment 1, 12 March 2021
PFIZER CONFIDENTIAL
Page 9
1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: A Phase 1 Study to Evaluate the Safety, Local and Systemic Tolerability, and 
PK of Multiple-Dose Topical Administration of PF-07038124 in Japanese Healthy 
Participants.
Rationale
The purpose of this study is to evaluate the multiple-dose safety, tolerability, skin irritation 
potential, and PK of PF-07038124, applied to Japanese healthy adult participants. This study 
will be randomized, vehicle-controlled, double-blinded to treatment assignment to permit an 
unbiased assessment of safety and tolerability.
Objectives and Endpoints
Objectives
Endpoints
Primary: 
Primary: 
•
To evaluate the safety, tolerability, and skin 
irritation potential of PF-07038124, following 
multiple doses applied topically, in Japanese 
healthy participants.
•
Incidence of treatment emergent AEs and SAEs, 
clinically significant changes in vital signs, ECG, 
and laboratory tests during the entire study.
•
Incidence and severity of local skin irritation at 
times indicated in SoA.
Secondary: 
Secondary: 
•
To characterize the PK of PF-07038124, 
following topical administration, in Japanese 
healthy participants.
•
PF-07038124 PK parameters following topical 
application on Days 1 and 10, as data permit: 
AUCtau, and Cmax, if applicable.
 
 
 
 
 
 
 
 
Overall Design
This is a Phase 1, randomized, double-blind, vehicle-controlled, parallel cohort study to 
evaluate the safety, tolerability, skin irritation potential, and PK of PF-07038124 in Japanese 
healthy adult participants. Both cohorts can be conducted simultaneously.
This study will evaluate the safety, tolerability, skin irritation potential and PK following 
application of PF-07038124 at 0.01% concentration and vehicle to 2000 cm2 (Cohort 1; 
approximately 10% BSA) or 4000 cm2 (Cohort 2; approximately 20% BSA).
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Number of Participants
A sample size of 12 participants (4 PF-07038124: 2 vehicle per cohort) has been selected 
empirically to permit adequate characterization of safety, tolerability, skin irritation potential, 
and PK at each dose level in Japanese healthy participants. Participants who discontinue prior 
to completion of the study for non-safety related reasons may be replaced, at the discretion of 
the PI and Sponsor.
Intervention Groups and Duration
Participants will be randomized to receive PF-07038124 or vehicle in a ratio of 
4 PF-07038124: 2 vehicle, per cohort. Each participant will receive multiple doses of 
PF-07038124 or vehicle starting on Day 1 topically applied for 10 consecutive days; applied 
QD in the AM for Cohort 1 and Cohort 2.  
The total participation time for each participant is approximately 66 days, including the 
screening period of up to 28 days, the double-blind treatment period of 10 days, and the
follow-up period of 28 days from last dose of the study intervention.
Participants will be screened within 28 days prior to application of the study intervention to 
confirm that they meet the selection criteria for the study. Participants will be admitted to the 
CRU at least 12 hours prior to their planned dose application time, and will be required to 
remain in the CRU until completion of procedures on Day 11 as described in the SoA.
Data Monitoring Committee or Other Independent Oversight Committee: No
Statistical Methods
All analyses described below will be conducted by treatment and cohort.  In addition, data 
from vehicle in Cohort 1 and Cohort 2 will be pooled.
All safety analyses will be performed on the safety analysis set, which is defined as all 
participants randomly assigned to study intervention and who take at least 1 dose of study 
intervention.  Participants will be analyzed according to the product they actually received.  
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
The primary endpoints of this study are treatment emergent AEs and SAEs, clinically 
significant changes in vital signs, ECG, laboratory tests, and incidence and severity of local 
skin irritation.
The primary endpoints will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and/or graphical presentations in 
order to evaluate the safety, tolerability, and skin irritation potential of PF-07038124.


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Protocol C3941003
Final Protocol Amendment 1, 12 March 2021
PFIZER CONFIDENTIAL
Page 11
The PK parameters for PF-07038124 following multiple-dose topical application will be 
derived from the plasma concentration-time profiles.  PK parameters 
 of 
PF-07038124 will be descriptively summarized by treatment group and nominal time, as 
appropriate.
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1.2. Schema
Figure 1.
Schema of Study C3941003
Screening
Randomized, Double-blind, Vehicle-controlled, Parallel cohort
Follow up
Day -28
Day 1
Day -1
Day 11
Day 10
Day 38 – 41
PF-07038124 0.01% QD or Vehicle QD to 2000 cm2 (approximately 10% BSA)
Cohort 1 
PF-07038124 0.01% QD or Vehicle QD to 4000 cm2 (approximately 20% BSA)
Cohort 2 


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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.
Schedule of Activities
Visit Identifiera
Abbreviations used in this table 
may be found in Appendix 8.
Screening
Treatment Phase
Follow-Upb
Early 
Termination/
Discontinuation
Days Relative to Day 1
-28 to -2
-1
1
2
3
4
5
6
7
8
9
10
11
38+3
Informed consent
X
CRU confinementc
X











Outpatient visit
X
Inclusion/exclusion criteria
X
X
X
Randomization
X
Medical/medication history 
(update) 
X
X
Physical examd
X
X
X
Height and weight
X
Review prior or concomitant 
treatments, as applicable
X












X
X
Safety laboratory, including 
fibrinogen and hsCRPe
X
X
X
X
X
X
Demography
X
Contraception check
X
X
X
X
X
Single, supine 12-Lead ECGf
X
X
X
X
X
X
Single, supine BP and pulse 
rate, and temperaturef
X
X
X
X
X
X
FSHg
X
Pregnancy test (WOCBP only)
X
X
X
X
HIV, HBsAg, HBcAb, HCVAb, 
syphilis
X
COVID-19 testing
Xh
X


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Final Protocol Amendment 1, 12 March 2021
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Visit Identifiera
Abbreviations used in this table 
may be found in Appendix 8.
Screening
Treatment Phase
Follow-Upb
Early 
Termination/
Discontinuation
Days Relative to Day 1
-28 to -2
-1
1
2
3
4
5
6
7
8
9
10
11
38+3
Urine drug test
X
X
Study intervention 
administration (QD)i
X
X
X
X
X
X
X
X
X
X
Skin Irritation Evaluationj
X
X
X
X
X
X
X
X
X
X
X
 
 
CRU dischargel
X
Serious and nonserious AE 
monitoringm
X
→
→
→
→
→
→
→
→
→
→
→
→
X
X
PK blood samplingn
X
X
X
X
X
X
X
a.
Day relative to start of study intervention (Day 1).
b.
All cohorts: Follow-up contact to occur 28-31 days post last dose with a phone call; additional follow-up at investigator discretion, including to monitor 
open AE, or based on emerging data.
c.
Participants will be admitted at least 12 hours prior to dosing. Admission procedures will be conducted once, unless deemed necessary by investigator or 
sponsor.
d.
Physical examination may be performed at non-specified timings if there are findings during the previous exam or new/open AEs, if appropriate and at 
investigator discretion. 
e.
For screening visit, test results must be reviewed and deemed acceptable in order to proceed with participation in study.
f.
12-lead ECGs, BP, pulse rate and temperature will be collected at screening.  For Days 1, 4, and 10, ECGs, BP, pulse rate, and temperature will be 
collected prior to and at approximately 6 hours post-dose.  Day 11 is 24 hours post-dose on Day 10 and is prior to discharge.  
g.
For confirmation of postmenopausal status only.
h.
COVID-19 viral test to occur between Day -5 and Day -3 to permit availability of test result prior to admission on Day -1.
i.
Study intervention (PF-07038124 or vehicle) will be applied QD in the AM.  Refer to Section 6.1.1 for additional details.
j.
Skin irritation assessment of the application sites will be conducted on Days 1-10 prior to each application of the study intervention and 24 hours post-dose 
on Day 10.  Refer to Section 8.2.5. 
 
l.
CRU discharge should occur following collection of PK sample at 24 hours post-dose on Day 10. Participants who have AEs or dermatological 
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Visit Identifiera
Abbreviations used in this table 
may be found in Appendix 8.
Screening
Treatment Phase
Follow-Upb
Early 
Termination/
Discontinuation
Days Relative to Day 1
-28 to -2
-1
1
2
3
4
5
6
7
8
9
10
11
38+3
observations on Day 11 will return to the CRU up to the discretion of the investigator, and follow-up contact will be made.
m. If unexpected reactions (eg, rash, hives) other than irritation reactions outlined in Table 4, Section 8.2.5 occur at an application site, the application site 
location must be recorded.
n.
Refer to Pharmacokinetic Sampling Schedule table below.
Pharmacokinetic Sampling Schedule
Visit Identifier 
Day
PK Blood Sampling
Hours Before/After AM Dose
0a
1
2
4
6
8
12
24
1 
X
X
X
X
X
X
X
X
4
X
X
7
X
X
10
X
X
X
X
X
X
X
X
a.
Predose sample collection.


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2. INTRODUCTION
PF-07038124 is a topical PDE4 inhibitor that is currently being developed for the treatment 
of AD and plaque psoriasis (psoriasis).
2.1. Study Rationale 
The purpose of this study is to evaluate the multiple-dose safety, tolerability, skin irritation 
potential, and PK of PF-07038124 in Japanese healthy participants.  This study will evaluate 
application of PF-07038124 and vehicle to a surface area of 2000 cm2 (approximately 10% 
BSA) and 4000 cm2 (approximately 20% BSA). These data will provide support for clinical 
development in Japanese participants with AD and psoriasis.
2.2. Background 
2.2.1. Role of Proinflammatory Cytokines in AD and Psoriasis
ATOPIC DERMATITIS: AD, also known as atopic eczema, is a common, chronic, 
inflammatory skin disorder characterized by flaky skin lesions, intense pruritus, and a general 
deterioration in quality of life.  AD can affect any age group.  Prevalence estimates suggest 
approximately 10% of adults and 10%-20% of children suffer from AD, and up to 18% of 
those affected with AD suffer with severe disease.  
There are a limited number of treatments available for AD.  Current treatments for AD 
include emollients, topical corticosteroids (eg, betamethasone, clobetasol, fluocinonide), 
topical calcineurin inhibitors (eg, pimecrolimus, tacrolimus), and coal tar preparations.  
Crisaborole ointment, 2% (weight by weight) (20 mg/g), a PDE4 inhibitor, is approved in the 
United States (US; Eucrisa®) as a topical treatment therapy in patients 3 months of age and 
older with mild to moderate AD; and in Canada (Eucrisa®), Israel, the EU, Australia and 
China (Staquis®) as a topical treatment therapy in patients 2 years of age and older with mild 
to moderate AD.  Additional treatments generally reserved for severe AD include 
phototherapy (eg, UVA light with or without psoralen) and systemic agents (eg, 
corticosteroids, cyclosporine, recombinant IFN-, mycophenolate mofetil, methotrexate).  
None of the currently available therapies offer a cure; therefore, the main aims of existing 
treatments are to reduce the occurrence of acute flares, increase the time between relapses, 
reduce pruritus and reduce the resulting sleep disturbances. 
For most AD patients not responding to topical therapies and phototherapy, off-label use of 
systemic agents, which includes both oral corticosteroids and oral immunosuppressants 
remain the last viable treatment option.  Dupilumab injection, an IL-4 receptor alpha 
antagonist, was approved for use in patients with moderate to severe AD.  Systemic therapy 
options are associated with potentially severe adverse effects and require careful monitoring.  
Therefore, the prominent unmet medical need in AD is for an effective, safe topical agent for 
once a day dosing without restrictions on long-term or continuous use, and without local or 
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The T-helper-2 response contribute to AD-associated skin inflammation and itch.1  The 
pathogenic role that the Th2 derived cytokines, IL-4 and IL-13, play in AD has been 
demonstrated through the clinical efficacy of dupilumab, an antibody to the IL-4 receptor that 
blocks the activity of both IL-4 and IL-13.2
PSORIASIS: The most common variant of psoriasis, plaque psoriasis (psoriasis vulgaris), is 
a chronic inflammatory skin disease characterized by red, scaly, raised plaques.  Chronic 
plaque psoriasis is a common skin disorder with a worldwide prevalence of 2%.  Although 
psoriasis primarily affects the skin and is not a life-threatening disease, it can profoundly 
impact the patient’s QoL resulting in an impairment akin to other major diseases, such as 
type 2 diabetes, myocardial infarction, and arthritis.  Current treatments for psoriasis include 
topicals, phototherapy, systemic non-biological therapies (methotrexate, cyclosporin, 
acitretin, apremilast [Otezla®]) and biologics.
Proinflammatory cytokines such as TNF-, IFN-and IL-23/T-helper-17 response cytokines 
play an important role in the pathogenesis of psoriasis.3  Several biologics monoclonal 
antibodies that target these proinflammatory cytokines have been shown to be effective for 
the treatment of psoriasis in clinical trials.4  Biologic agents used in the treatment of psoriasis 
include multiple anti-TNF agents (such as infliximab, adalimumab, etanercept), anti-IL-
12/IL-23 antibodies and anti-IL-17 antibodies.  PDE4 inhibitors such as apremilast (Otezla®) 
may reduce production of pro‐inflammatory TNF-and IFN-by increasing cAMP levels.
2.2.2. Description of Study Intervention: Mechanism of Action
PDE are a family of enzymes that breakdown the ubiquitous second messengers, cAMP and 
cGMP, that regulate various cellular processes.  PDE4 is a subfamily that includes the four 
isozymes, each encoded by separate genes, PDE4 A, B, C and D.  Inhibitors of the PDE4 
family have been the focus of intense drug development over many years due to their broad 
potential in inflammatory diseases such as AD and psoriasis.  For example, apremilast 
(Otezla®) is an oral small-molecule inhibitor of PDE4 that is approved for the treatment of 
patients with moderate to severe plaque psoriasis and active psoriatic arthritis.  Crisaborole 
(Eucrisa®, Staquis®) is a topically delivered PDE4 inhibitor that has demonstrated efficacy in 
clinical trials5 and is approved for the treatment of mild to moderate AD as described 
previously.  In addition, other topical PDE4 inhibitors, such as roflumilast (ARQ-151), have 
shown activity in the treatment of psoriasis.6
PF-07038124 is designed to be a best-in-class, oxaborole-based potent PDE4 inhibitor that 
has increased immunomodulatory activity in T-cell based assays, which correlates with 
inhibition of additional PDE family members that are active in immune cells.  This enhanced 
activity contributes to greater inhibition of cytokines IL-13 and IL-4 from activated T cells 
which may lead to increased clinical activity. 


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PF-07038124 is a potent and selective PDE4 inhibitor intended to be used for topical 
administration for the treatment of AD and psoriasis.  PF-07038124 inhibits the enzymatic 
activity of the PDE4 isoforms that have been tested with an IC50 of 0.505 nM and 0.3 nM on 
PDE4B and PDE4D, respectively.  PF-07038124 inhibits cytokine production and release 
from T cells and monocytes in PBMC over a range of concentrations that is dependent on the 
cytokine that is being modulated.  The IC50 for release of LPS stimulated TNF-is most 
sensitive with an IC50 of 0.15 nM.  The IC50’s for inhibition of IFN-, IL-4, and IL-13 from 
lectin stimulated PBMCs are 1, 4 and 135 nM, respectively.  PF-07038124 exhibited greater 
inhibitory activity on IL-13 release than was seen with other PDE4 specific inhibitors, 
consistent with its inhibitory activity on additional PDEs, such as PDE3 at higher 
concentrations.  PF-07038124 increased the level of cAMP in human PBMCs in a dose 
dependent manner, consistent with its primary mechanism of action as a PDE inhibitor.  
An ex vivo human skin model of Th2 inflammation was used to measure the activity of 
PF-07038124 in its ointment formulation with topical application.  This model has been used 
to test the activity of other topical therapeutic compounds, including topical corticosteroids, 
JAK inhibitors and the PDE4 inhibitor crisaborole (Eucrisa®).  In this model system with a 
single dose application on excised human skin 20 hours prior to stimulation of the T cells in 
the skin tissue, PF-07038124 inhibited inflammatory cytokine gene expression at the dose 
strengths of 0.1, 0.06, 0.03 and 0.01%, with little to no activity at 0.001% strength relative to 
the vehicle (placebo) control. 
Based on its cytokine inhibition profile, topical administration of PF-07038124 is anticipated 
to provide potential therapeutic benefit in the treatment of AD and psoriasis by targeting the 
T-helper-2 response cytokines and TNF-α.
2.2.3. Preclinical Safety Data 
In the pivotal 3-month toxicity studies in rats (oral) and minipigs (dermal), the systemic 
NOAEL were identified as 4 mg/kg/day and 0.0104 mg/cm2/day (0.0052 mg/cm2, BID) to 
10% BSA, respectively, with systemic exposures of 2x and 1.2x, respectively, the projected 
maximum human exposure (uCav = 9 pg/mL).  The systemic NOAEL exposure identified in 
the more sensitive nonclinical species (minipig) was 11 pg/mL (Cav, unbound).  The local 
(dermal) NOAEL was identified at the 0.03% concentration (BID) corresponding to 
0.0052 mg/cm2/day (0.0026 mg/cm2, BID) and represents an 17x multiple to the projected 
maximum human dermal dose of 0.0003 mg/cm2/day in the current study.  Based on the 
completed nonclinical studies, local (skin) and systemic (cardiovascular, nervous, and 
gastrointestinal) target organs/systems were identified.  Local reactions (erythema, edema) 
were observed in minipigs at ≥0.00174 mg/cm2/day (5.8x the highest planned clinical dermal 
dose, 0.0003 mg/cm2/day).  A potential for skin sensitization by PF-07038124 was identified 
in a mouse local lymph node assay with a NOEL of 0.015 mg/cm2/day (50x the highest 
planned clinical dermal dose, 0.0003 mg/cm2/day). Cardiovascular effects included increases 
in heart rate, contractility, and/or blood pressure in rats and/or dogs, and vascular 
injury/compromise (in mesentery, kidney, adrenal gland, and/or bladder) in rats and/or 
minipigs.  Clinical signs indicative of nervous system effects (eg, ataxia, decreased activity, 
hunched posture, twitching, and/or tremors) and gastrointestinal effects (emesis, salivation, 


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and/or soft/liquid feces) were also observed in rats, dogs, and/or minipigs, mostly at 
non-tolerated doses.  These systemic effects in nonclinical species are consistent with those 
reported for oral selective PDE4 inhibitors.  PF-07038124 was negative for mutagenicity, 
positive in an in vitro micronucleus assay at high concentrations via aneugenic mechanism, 
but negative in an in vivo rat micronucleus assessment.  PF-07038124 was not phototoxic 
and no further photosafety testing is recommended.  Rat and rabbit EFD was assessed after 
oral administration of PF-07038124 to pregnant animals.  PF-07038124 did not cause any 
effects on EFD following oral administration at doses up to 4 mg/kg/day (rats) and 8 
mg/kg/day (rabbits), respectively.  The developmental NOAEL exposures in pregnant rats 
and rabbits corresponded to 1.7x and 2.7x the maximum planned clinical exposure on an 
uCav basis.  In addition, no effects on fertility were observed in female rats after oral 
administration of PF-07038124 up to 4 mg/kg/day (4.1x the maximum planned dose on an 
uCav comparison basis).
The nonclinical safety profile of PF-07038124 has been adequately characterized to support 
progression into clinical trials of up to 3 months. 
2.2.4. Clinical Overview
To date the clinical experience with PF-07038124 comprises one Phase 1 study in adult 
healthy Western participants designated C3941001; a multiple ascending dose study 
following topical administration.
PF-07038124 was generally safe and well tolerated in healthy participants (C3941001).  
There were no clinically meaningful findings in vital signs, ECG, or laboratory tests reported 
during this study.  A summary is provided in Table 1 below, further details are provided in 
the current IB.
Table 1.
PF-07038124 Clinical Development Program – Completed Studies as of 
January 2021
Study ID
Description
PF-07038124 Dose/Regimen
Number of Participants
C3941001 
(completed)
The study consisted of 
2 parts:
Part A: 
Randomized, double-blind, 
sponsor-open, 
vehicle-controlled multiple 
doses application to assess 
skin irritation.
Part B:
Randomized, double-blind, 
sponsor-open, 
vehicle-controlled multiple 
doses application to assess 
safety, tolerability, PK, and 
skin irritation.
Part A: 0.06% BID applied to 
20 cm2 (0.1% BSA) for 7 
days.
Part B: 0.01% QD and BID, 
and 0.03% QD applied to 
2000 cm2 (10% BSA), as well 
as 0.01% QD applied to 
4000 cm2 (20% BSA) for 
10 days.
8 (active and vehicle).
26 (8/cohort; 6 active and 
2 vehicle, only 2 at 
0.01% QD (20% BSA)).


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2.2.4.1. Clinical Safety
In Study C3941001, PF-07038124 ointment was evaluated in Part A for the potential of skin 
irritation upon applying 0.06% BID for 7 days to 0.1% BSA and the evaluation of safety, 
tolerability and PK in Part B where the drug was applied at 0.01% QD and BID to 10 and 
20% BSA and at 0.03% QD to 10% BSA.  In the Part A PF-07038124 0.06% BID group, 
skin abrasion and skin irritation were reported by 2 participants.  The most commonly 
reported all treatment-related AEs following 10 days of topical application of the 
PF-07038124 ointment during Part B across active healthy participants were skin irritation; 
including acne and erythema, which were reported as all mild.  Mild systemic AEs were also 
reported including headache, dizziness, and nausea, but were considered unrelated to study 
intervention.  There were no deaths or SAEs reported in this Phase 1 study.  Please refer to 
the IB for further details from the C3941001 study.  
2.2.4.2. Clinical Pharmacokinetics
Following multiple topical administration of PF-07038124 following 10 days of dosing, the 
majority of concentrations on Day 1 were BLQ and a limited number of participants had 
valid parameter values.  PF-07038124 was absorbed rapidly followed by a biexponential 
decline, with Cmax achieved at a median Tmax of 4 to 6 hours for treatments where median 
values could be reported.  Individual values ranged between 2 to 8 hours for all treatments.  
For the 0.01% QD (Cohort 1), 0.01% BID (Cohort 2), and 0.03% QD (Cohort 3) cohorts, 
geometric mean Cav on Day 10 was 37.43, 88.82, and 187.1 pg/mL, respectively in Table 2.  
Individual t½ on Day 10 ranged from 8.49 to 17.4 hours for treatments where t½ could be 
reported.  Geometric mean CL/F values ranged from 400.5 to 668.4 L/hr for treatments 
where mean values could be reported. In general, plasma PF-07038124 exposure appeared to 
increase in a greater than dose-proportional manner for AUCtau, and an approximate 
dose-proportional manner for Cmax. 
Individual accumulation ratios were 3.59 for AUCtau (Rac) and ranged from 2.69 to 35.8 for 
Cmax (Rac,Cmax), respectively on Day 10.  The PF-07038124 median trough plasma 
concentrations approached steady state following 10 days of dosing.
Table 2.
Descriptive Summary of Day 10 Plasma PF-07038124 PK Parameters, 
C3941001
Day 10 PK 
Parametera,b
Part B Cohort 1 
(2000 cm2) 
PF-07038124 
0.01% QD (N=6)
Part B Cohort 2 
(2000 cm2) 
PF-07038124 
0.01% BID (N=6)
Part B Cohort 3 
(2000 cm2) 
PF-07038124 
0.03% QD (N=6)
Part B Cohort 4 
(4000 cm2) 
PF-07038124 0.01% 
QD (N=2)
AUCtau
(pg.hr/mL)
897.2 (44)
1068 (44)
4491 (57)
N/A
Cav (pg/mL)
37.43 (44)
88.82 (44)
187.1 (57)
N/A
Cmax (pg/mL)
52.78 (59)
104.7 (49)
264.7 (70)
48.8, 96.0b


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Ctrough
(pg/mL)
26.95 (48)
87.73 (47)
147.4 (66)
41.8, 86.2b
a.
Geometric mean (geometric %coefficient of variation)
b.
Individual values are listed when there are less than 3 evaluable measurements.
2.3. Benefit/Risk Assessment
PF-07038124 is not expected to provide any clinical benefit to healthy participants.  This 
study is designed primarily to generate safety, tolerability, skin irritation potential, and 
pharmacokinetic data for further clinical development.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of PF-07038124 may be found in the IB, which is the SRSD for this 
study. 


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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention PF-07038124
Adverse Nonclinical findings – PDE4 inhibitor 
associated vasculitis
Vasculitis is an effect associated with 
administration of oral PDE4 inhibitors in 
nonclinical species, correlates with an acute phase 
reaction, and occurs at doses above the NOAEL 
and also systemic exposures at the clinical 
MRHD for oral PDE4 inhibitors.
Participants will be assessed for safety throughout 
the study (including monitoring of acute-phase 
reactions such as fibrinogen and C-reactive protein). 
Adverse Nonclinical findings – PDE4-related 
nervous system and gastrointestinal effect (a class 
effect of AEs observed with PDE4 inhibitors)
Clinical signs indicative of nervous system effects 
(eg, ataxia, decreased activity, hunched posture, 
twitching, and/or tremors) and gastrointestinal 
effects (emesis, salivation, and/or soft/liquid 
feces) were observed in rats, dogs, and/or 
minipigs, at non-tolerated doses.
Participants will be assessed for safety throughout 
the study.
Nonadverse Nonclinical findings – PDE4-related 
cardiovascular effect
Cardiovascular effects (eg, increases in heart rate, 
contractility, and/or blood pressure) in rats and/or 
dogs.  A NOEL for the heart rate effect was not 
determined in either species.
Participants will be assessed for safety throughout 
the study.
Adverse Nonclinical findings – Potential Skin 
Sensitization
The potential for skin sensitization was identified 
as a risk in nonclinical species at dermal 
concentrations 50x above the planned dose 
concentration of 0.01%, with a no observed effect 
level of 0.06% ointment.
Participants will be assessed for safety 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 study interventions 
will be excluded from the study.
Other
Risk of COVID-19 exposure during study
During the pandemic, study participants could be 
infected with the SARS-CoV-2 virus during study 
participation. This could lead to increased health 
risk for this participant and others in the study.
Participants undergo COVID-19 specific 
assessments prior to admission to study site and Day 
4 according to SoA.


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2.3.2. Benefit Assessment
While PF-07038124 is not expected to provide any clinical benefit to healthy participants, 
this study is designed to generate the safety, tolerability, skin irritation potential, and PK data 
of PF-07038124 in Japanese healthy participants for further clinical development.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in association with PF-07038124 are justified by the 
anticipated benefits that may be afforded to participants with AD and psoriasis.
3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 
•
To evaluate the safety, tolerability, and skin 
irritation potential of PF-07038124, following 
multiple doses applied topically, in Japanese 
healthy participants.
•
Incidence of treatment emergent AEs and SAEs, 
clinically significant changes in vital signs, ECG, 
and laboratory tests during the entire study.
•
Incidence and severity of local skin irritation at 
times indicated in SoA.
Secondary:
Secondary: 
•
To characterize the PK of PF-07038124, 
following topical administration, in Japanese 
healthy participants.
•
PF-07038124 PK parameters following topical 
application on Days 1 and 10, as data permit: 
AUCtau, and Cmax, if applicable.
 
 
 
 
 
 
 
 
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1, randomized, double-blind, vehicle-controlled, parallel cohort study to 
evaluate the safety, tolerability, skin irritation potential, and PK of PF-07038124 in Japanese 
healthy adult participants. Both cohorts can be conducted simultaneously.
This study will evaluate the safety, tolerability, skin irritation potential and PK following 
application of PF-07038124 at 0.01% concentration and vehicle to 2000 cm2 (Cohort 1; 
approximately 10% BSA) or 4000 cm2 (Cohort 2; approximately 20% BSA).
Participants will be randomized to receive PF-07038124 or vehicle in a ratio of 
4 PF-07038124: 2 vehicle, per cohort. Each participant will receive multiple doses of 
CCI


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PF-07038124 or vehicle starting on Day 1 topically applied for 10 consecutive days; applied 
QD in the AM for Cohort 1 and Cohort 2.  Participants will not be randomly assigned to 
cohort.  The first group of participants will be enrolled Cohort 1 followed by Cohort 2. All 
participants will have the study interventions randomly assigned, for the purpose of 
determining skin irritation potential, as well as PK, safety and tolerability. 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. 
The total participation time for each participant is approximately 66 days, including the 
screening period of up to 28 days, the double-blind treatment period of 10 days, and the 
follow-up period of 28 days from last dose of the study intervention.
Approximately 12 Japanese healthy adult participants are planned to participate in this study.
Participants will be screened within 28 days prior to application of the study intervention to 
confirm that they meet the selection criteria for the study. Participants will be admitted to the 
CRU at least 12 hours prior to their planned dose application time (see Section 6.1.1), and 
will be required to remain in the CRU until completion of procedures on Day 11 as described 
in the SoA.
Participants will be followed-up with a phone call per the SoA following the last dose of 
study intervention to assess for AEs, SAEs, concomitant treatments, and contraception check.  
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.
4.2. Scientific Rationale for Study Design
The purpose of this study is to evaluate the multiple-dose safety, tolerability, skin irritation 
potential, and PK of PF-07038124, applied to Japanese healthy adult participants. This study 
will be randomized, vehicle-controlled, double-blinded to treatment assignment to permit an 
unbiased assessment of safety and tolerability.
Although no significant differences related to safety, tolerability, skin irritation potential or 
PK are expected between Japanese and Westerner healthy adult participants, this study can 
provide a preliminary characterization of the safety, tolerability, skin irritation potential, and 
PK profile of PF-07038124 to support potential inclusion of Japanese participants in future 
studies. 
This study consists of two cohorts to evaluate two administration areas of PF-07038124 
applied to 2000 cm2 (approximately 10% BSA) and 4000 cm2 (approximately 20% BSA) in 
parallel.  This approach is based on the result of C3941001 study which was generally safe 
and well tolerated in Westerner healthy participants.
Assessment of clinical safety laboratory tests (Appendix 2), vital signs, 12-lead ECG, 
physical examinations, and AE monitoring will provide essential data to evaluate the safety 
and tolerability of PF-07038124 following topical application.  Based on the findings from 


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the toxicology studies, fibrinogen and C-reactive protein will be added to safety laboratory 
assessments as a precaution to monitor for inflammation.
COVID-19 specific assessments have been incorporated to minimize the risks of COVID-19 
related complications to participants and the study site personnel.
Human reproductive safety data are limited for PF-07038124, but there is no suspicion of 
human teratogenicity based on the intended pharmacology of the compound. In addition, 
EFD studies conducted in pregnant rats and rabbits at exposures that correspond to 1.7x and 
2.7x the maximum planned clinical exposure did not cause any effects on embryo-fetal 
development. See Appendix 4 for contraceptive requirements.
Banked Biospecimens will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
The nonclinical safety profile of PF-07038124 following systemic administration (oral) to 
rats and topical application (dermal) to minipigs supports human clinical studies of up to 3 
months in duration (See Section 2.2.3). The dose proposed for this study was determined 
considering all relevant information obtained from nonclinical safety studies, incorporating 
the NOAEL from 3-month studies in minipigs, together with the systemic exposure observed 
following topical application of PF-07038124 to healthy participants.  As a result, the dose 
strength of PF-07038124 selected for this study is 0.01%, applied once daily. 
Regarding the high-dose cohort (Cohort 2), PF-07038124 at 0.01% concentration to 
4000 cm2 (approximately 20% BSA), has been selected to evaluate the safety and tolerability 
of PF-07038124 in Japanese healthy adult participants so that safety and tolerability can be 
examined in the dose range including the maximum potential dose in the planned global late 
phase studies.  And regarding the low-dose cohort (Cohort 1), PF-07038124 at 0.01% 
concentration to 2000 cm2 (approximately 10% BSA), has been selected to allow the direct 
comparison of PK with Cohort 1 (0.01% QD to 10% BSA) of FIH study.
Summarized in Table 3 are the predicted exposures and safety margin for the 0.01% dose 
strength in this protocol following topical application of PF-07038124.  The overall estimate 
of systemic exposure of PF-07038124 is based upon the systemic exposure observed in 
healthy participants, drug concentration and application area (eg, 10% BSA) with an 
application rate of 3 mg/cm2.
The systemic exposure of PF-07038124 was predicted as the topically applied QD dose of 
0.01% applied to 2000 and 4000 cm2 (approximately 10% and 20% BSA, respectively). The 
clinical exposure limit for this study is based on the systemic NOAEL of 0.06% (0.0104 
mg/cm2/day) with a corresponding systemic exposure (Cav free) of 11 pg/mL following 3 
months of twice daily topical administration in minipigs (see Section 2.2.3).


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Table 3.
Proposed Doses, Predicted Free Exposures, and Safety Margins following 
QD Topical Application of PF-07038124a
Formulation 
Strength 
(%)
Population
BSA (cm2, %)
Dose 
Applied 
(mg/day)
Total 
AUC24
(pg•hr/mL)
Cav
total
(pg/mL)
Cav free
(pg/mL)
Predicted 
Cav free 
Safety 
Margin
0.01 QD
Healthy
participants
2000 cm2 (10%)
0.6
897.2
37.43
1.8
6.1
0.01 QD
Healthy
participants
4000 cm2 (20%)
1.2
1794
74.86
3.6
3.1
a. Assume QD dosing.  
NOAEL exposure in minipig was 11 pg/mL. 
Maximum application rate of formulation: 3 mg/cm2.
Maximum concentration: 0.01% (0.1 mg PF-07038124/g formulation).
Topical daily dose = BSA (cm2) × formulation concentration (µg/mg) × formulation applied 
(mg/cm2).
Fraction unbound in plasma (fup) = 0.0482, molecular weight (MW)=327, where Cav
free = AUC/24hr × fup.
Based on the PK findings in the FIH study (C3941001), the free Cav exposure was 
approximately 1.8 pg/mL at the 0.01% formulation upon application to 10% BSA.  The 
predicted exposure margin at the 0.01% formulation following QD is approximately 6-fold
and 3-fold for 2000 cm2 and 4000 cm2 respectively, relative to the NOAEL exposure in the 
minipig.  
The projected systemic Cav concentrations following 0.01% QD topical application to 
20% BSA is less than the observed systemic Cav concentrations (Study C3941001: Total 
Cav = 187 pg/mL; free ~9 pg/mL) at 0.03% QD topical application to healthy participants, 
which was well tolerated.  As a result, there is low potential that participants could 
experience PDE4-related side effects. 
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 Follow-Up.
The end of the study is defined as the date of the Follow-Up of the last participant in the 
study.
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.


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Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male and female participants must be 20 to 55 years of age, inclusive, at the time of 
signing the ICD.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Male and female participants who are overtly healthy as determined by medical 
evaluation including medical history, physical examination, laboratory tests, and 12-
lead ECG.
3. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Participants must have 4 biologically Japanese grandparents who were born in Japan.
Weight:
5. BMI of 17.5 to 25 kg/m2; and a total body weight >50 kg (110 lb).
Informed Consent:
6. 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. 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.


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2. Participants who have a history of or have active forms of dermatitides/eczematous 
conditions (eg, contact dermatitis, seborrhhoeic, discoid, gravitational, asteatotic and 
dishydrotic eczema) or other inflammatory skin diseases(eg, psoriasis, viral infection, 
fungal infection, bacterial infection) that would interfere with evaluation of the test 
site reaction.
3. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
4. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, 
HBcAb, HCVAb, or syphilis at screening.  Hepatitis B vaccination is allowed.
5. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
6. Acute disease state (unstable medical condition such as nausea, vomiting, fever or 
diarrhea, etc) within 7 days of Day 1.
7. Have undergone significant trauma or major surgery within 4 weeks of screening.
Prior/Concomitant Therapy:
8. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention.  (Refer to Section 6.5 for additional details).
Prior/Concurrent Clinical Study Experience:
9. Previous administration with an investigational drug within 4 months (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:
10. A positive urine drug test at screening and/or Day -1.
11. 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.
12. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may
affect participant safety or interpretation of study results (eg, baseline QTcF interval 


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>450 msec, complete LBBB, signs of an acute or indeterminate-age myocardial
infarction, ST-T interval changes suggestive of myocardial ischemia, second- or 
third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias).  If the 
baseline uncorrected QT interval is >450 msec, this interval should be rate-corrected 
using the Fridericia method and the resulting QTcF should be used for decision 
making and reporting.  If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the 
ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values 
should be used to determine the participant’s eligibility.  Computer-interpreted ECGs 
should be overread by a physician experienced in reading ECGs before excluding 
participants.
13. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat test, if deemed necessary:

AST or ALT level ≥1.5 × ULN;

Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert’s 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is≤ULN.
14. A positive COVID-19 test at screening.
Other Exclusions:
15. 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).
16. Blood donation (excluding plasma donations) of approximately ≥400 mL within 3 
months or ≥200 mL within a month prior to dosing.  Additionally, approximately 
≥400 mL within 4 months for female participants.  
17. History of serious adverse reactions or hypersensitivity to any topical drug; or known 
allergy to any of the study intervention or any components in the study intervention or 
history of hypersensitivity; or allergic reactions to any of the study preparations.
18. Not willing to refrain from shaving (Note: shaving around face is permitted), 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.


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19. History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin 
is planned to flush intravenous catheters.
20. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol.
21. 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 4 hours prior 
to any safety laboratory evaluations.

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.
5.3.3. Activity

Showering/Bathing: Participant’s dosing areas are required to be dry for at least 
30 minutes prior to each study intervention application.  To help facilitate this, 
participants will not be permitted to shower or bathe within 2 hours prior to and 
4 hours after any study intervention 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 2 hours prior to the AM dose.  Participants will be allowed 
to take a shower on Day -1 prior to the first application of the study intervention.

The use of any products in the area where the study intervention is applied is 
prohibited during confinement in the CRU.

Participants should be encouraged not to touch the area of application.


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
Participants should be encouraged not to put hands in the mouth to avoid ingestion of 
study intervention.

Participants should avoid wiping the study intervention off the skin until 4 hours post-
dose.

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 that may cause either the 
study medication to be 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 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use.  At time points indicated in the 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).  In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention/enrolled in the study. Screen 
failure data are collected and remain as source and are not reported to the clinical database.
Individuals who do not meet the criteria for participation in this study (screen failure) may 
not be rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to PF-07038124 0.01% ointment 
and PF-07038124 vehicle ointment.


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6.1. Study Intervention(s) Administered
Intervention Name
PF-07038124 0.01% ointment
PF-07038124 vehicle ointment
ARM Name
(group of patients receiving a specific 
treatment (or no treatment)
Active
Vehicle
Type
Drug
Drug
Dose Formulation
Ointment
Ointment
Unit Dose Strength(s)
0.1 mg/g ointment in 60-gram tube
0 mg/g ointment in 60-gram tube
Dosage Level(s)
0.01% (wt/wt), QD
0% (wt/wt), QD
Route of Administration
Topical
Topical
Use
Experimental
Placebo
IMP or NIMP
IMP
IMP
Sourcing
Provided centrally by the sponsor.
Provided centrally by the sponsor.
Packaging and Labeling
Study intervention will be provided in 
cartons.  Each carton will contain one 
tube.  Both the carton and tube will be 
labeled in a blinded format as 
required per country requirement.
Study intervention will be provided 
in cartons.  Each carton will contain 
one tube.  Both the carton and tube 
will be labeled in a blinded format as 
required per country requirement.
PF-07038124 topical ointment, 0.1 mg/g will be provided as the active ingredient with 
precedented excipients: white petrolatum, mono- and di-glycerides, hexylene glycol and 
paraffin wax.
Vehicle (placebo, no active drug in the formulation) topical ointment will be provided as the 
precedented excipients only: white petrolatum, mono- and di-glycerides, hexylene glycol and 
paraffin wax.
PF-07038124 and vehicle ointments will be supplied by Pfizer to the CRU as 60 gram tubes
and labeled according to local regulatory requirements in a blinded fashion.
During the stay in the CRU, study intervention applications will be performed by trained 
study staff to ensure proper study intervention application.
6.1.1. Administration
6.1.1.1. Study Treatment Regimen
The study intervention will be applied in blinded fashion, at the CRU. All applications of the 
study intervention will be dispensed and applied by study site staff from Day 1 through 
Day 10 dose.  Every effort must be made for the dose applications on Days 2-10 to be 
completed at 24±2 hour intervals from the recorded time of completion of the Day 1 dose 
application, for each participant.  
The study intervention will be applied QD for 10 consecutive days from Day 1 AM through 
Day 10 AM. 
The per application dose will be calculated using the formula provided below in 
Section 6.1.1.2. The intended dose of the study intervention application is approximately 


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3 mg/cm2. The study intervention should be applied evenly to all identified areas. The per 
application dose will be expressed as the weight of ointment in grams. The per application 
dose will remain fixed and the study intervention will be applied to the areas identified on 
Day 1.
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 × 0.003 (g/cm2) = Weight of study intervention (in g) per application.
where BSA is 2000 cm2 for Cohort 1, and 4000 cm2 for Cohort 2.
6.1.1.3. Application of Study Intervention
Before the Day 1 AM dose is applied for each participant, the designated areas for treatment 
will be identified on Day 1 and documented in the participant’s study records. For each 
subsequent study intervention application, study site staff will refer to the documented 
locations as determined on Day 1.
The application area will include a treatment area of 2000 cm2±200 cm2 (approximately 10% 
BSA) for Cohort 1. For Cohort 2, the treatment area is 4000 cm2±400 cm2 (approximately 
20% BSA).  The study intervention will be applied for 10 consecutive days.  The application 
area will include the back as well as other extremities, abdomen and/or chest, identified by 
the investigator.
Wearing gloves, study site staff will apply the per application dose to the surface area 
determined on Day 1.  Study intervention will be applied as a thin layer of participant’s skin. 
Care must be taken to avoid study intervention 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 study intervention application, participants will be 
instructed to wear loose-fitting clothing, to not wipe study intervention off the skin, and to 
refrain from bathing, sauna or washing the treated areas within 4 hours after application.  At 
4 hours post-dose, study intervention will be wiped from all application sites, with a clean 
towel, prior to participants being released to shower.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 


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minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken.  The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible.  Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention.  Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. The head of the medical institution (where applicable) or study intervention 
administrator is responsible for study intervention accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records), such as 
the IPAL or sponsor-approved equivalent. All study interventions will be accounted 
for using a study intervention accountability form/record.
7. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual.  All destruction must be adequately 
documented.  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP Manual.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff.  Dispensing is defined as the provision of study intervention, concomitant treatments, 
and accompanying information by qualified staff member(s) to a healthcare provider, 
participant in accordance with this protocol.  Local health authority regulations or 
investigator site guidelines may use alternative terms for these activities.
The study intervention will be dispensed in a blinded fashion using an IRT system at the 
study days as summarized in the SoA.  A qualified staff member will dispense the study 


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intervention via unique container numbers on the cartons provided.  A second staff member 
will verify the dispensing.
Prior to application, the per application dose will be carefully weighed out by the qualified 
CRU staff. Blinded study intervention will be applied to the participant. 
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation of participants to treatment groups will proceed through the use of an IRT system 
(IWR).  The site personnel (study coordinator or specified designee) will be required to enter 
or select information including but not limited to the user’s ID and password, the protocol 
number, and the participant number.  The site personnel will then be provided with a 
treatment assignment, randomization number, and DU or container number when study 
intervention is being supplied via the IRT system.  The IRT system will provide a 
confirmation report containing the participant number, randomization number, and DU or 
container number assigned.  The confirmation report must be stored in the site’s files.  Study 
intervention will be dispensed at the study days as summarized in the SoA.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.3.2. Breaking the Blind
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
treatment assignment is warranted. Participant safety must always be the first consideration 
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a 
participant’s treatment assignment unless this could delay further management of the 
participant. If a participant’s treatment assignment is unblinded, the sponsor must be notified 
within 24 hours after breaking the blind. The date and reason that the blind was broken must 
be recorded in the source documentation and CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
The study intervention will be applied by the investigator site personnel.  The application site 
of each participant will be examined following dosing by the second staff member to ensure 
the study intervention was topically applied.  The date and time of each dose administered in 
the clinic will be recorded in the source documents and recorded in the CRF.  The dose of 
study intervention and study participant identification will be confirmed at the time of dosing 
by a member of the study site staff other than the person administering the study intervention.


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6.5. Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention.  Limited use of nonprescription medications that are not believed to affect 
participant safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor.  Acetaminophen/paracetamol may be used at doses of 
≤1 g/day.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.  All participants will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment.  Treatments taken after the first dose of study intervention
will be documented as concomitant treatments.
6.5.1. Rescue Medicine
There is no rescue therapy to reverse the AEs observed with PF-07038124; standard medical 
supportive care must be provided to manage the AEs. 
6.6. Dose Modification
Not applicable.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following: Liver injury, ECG changes, local tolerability, and AEs.
Note that discontinuation of study intervention does not represent withdrawal from the study.  
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for follow up. See the SoA for data to be collected at the time of 
discontinuation of study intervention and follow-up for any further evaluations that need to 
be completed.


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In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information.
The site will inform the Sponsor Medical Monitor or Sponsor Clinician if the below criteria 
for permanent discontinuation of the study intervention are triggered.
Liver Injury
Please refer to Appendix 6 for Potential Cases of Drug-Induced Liver Injury (DILI; Hy’s 
law). 
ECG Changes
A participant who meets either bulleted criterion based on the average of triplicate ECG 
readings will be withdrawn from the study intervention. 

QTcF >500 msec.

Change from baseline: QTc >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.
Local Tolerability 
If a participant experiences severity Score 4 (Strong to severe) on the local tolerability 
assessment (Section 8.2.5), study treatment will be discontinued permanently, and participant 
will proceed to Early Termination/Discontinuation visit and follow-up as described in SoA. 
If a participant experiences application site reaction of Score 3 (Moderate) on the local 
tolerability assessment, investigator may temporarily discontinue application of the study 
intervention for up to 5 consecutive days. If temporary withholding of the study intervention 
occurs for more than 5 consecutive days, then the participant should be permanently 
withdrawn from treatment and should follow-up with the site until complete or near complete 
resolution of the AE.  This dosing gap may occur only once for the same participant.
AEs
Hypersensitivity Reactions: If signs and symptoms of hypersensitivity are attributable to the 
study intervention, including contact urticaria, it must be discontinued immediately, and 
appropriate therapy initiated. 


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Additional instances of temporary discontinuation may be appropriate (eg, surgery, infection, 
etc.).
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study.  Participants should be questioned regarding 
their reason for withdrawal.  
The participant will be permanently discontinued both from the study intervention and from 
the study at that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 


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should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 
and/or posttreatment study follow-up, and entered on the appropriate CRF page.  In the event 
that vital status (whether the participant is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed 
in accordance with local law.
7.3. Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 


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record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention 
to confirm that they meet the study population criteria for the study.  If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.
A participant who qualified for this protocol but did not enroll from an earlier cohort/group 
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study.  In 
addition, other clinical assessments or specimen collections, eg, banked biospecimens, may 
be used without repeat collection, as appropriate.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately 
180 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.


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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 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. 
Physical examinations may be conducted by a physician. 
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. 
8.2.2. Vital Signs
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest.  The same arm 
(preferably the dominant arm) will be used throughout the study.  Participants should be 
instructed not to speak during measurements.  
The same properly sized and calibrated BP cuff will be used to measure BP each time.  The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds.  When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
8.2.2.1. Temperature
Temperature (oral or axillary) will be measured.  No eating, drinking, or smoking is allowed 
for 15 minutes prior to the measurement.
8.2.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, QT, and QTcF intervals and QRS 
complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) is not 
recommended given the potential risk of discrepancies with ECGs acquired using standard 


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limb lead placement.  All scheduled ECGs should be performed after the participant has 
rested quietly for at least 10 minutes in a supine position. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements.  Additional ECG monitoring will occur if a) a 
postdose QTcF interval is increased by ≥60 msec from the baseline and is >450 msec; or b) 
an absolute QTcF value is ≥500 msec for any scheduled ECG.  If either of these conditions 
occurs, then 2 additional ECGs will be collected approximately 2 to 4 minutes apart to 
confirm the original measurement.  If the QTcF values from these repeated ECGs remain 
above the threshold value, then a single ECG must be repeated at least hourly until QTcF 
values from 2 successive ECGs fall below the threshold value that triggered the repeat 
measurement.
If a) a postdose QTcF interval remains ≥60 msec from the baseline and is >450 msec; or b) 
an absolute QTcF value is ≥500 msec for any scheduled ECG for greater than 4 hours (or 
sooner, at the discretion of the investigator); or c) QTcF intervals get progressively longer, 
the participant should undergo continuous ECG monitoring.  A cardiologist should be 
consulted if QTcF intervals do not return to less than the criterion listed above after 8 hours 
of monitoring (or sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read 
QTcF value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in 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 2 days after the last dose of study intervention should be 


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repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
8.2.5. Skin Irritation Assessment
Local toleration will be assessed by Draize scoring and clinical observation in Table 4. 7  
The dermatologists will assess local toleration at the treatment test areas by examining the 
skin under standard light conditions (eg, using a 100-Watt incandescent blue bulb) 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.  The same dermatologist
should do all the skin response grading for any given participant during the course of the 
study, if possible.  The skin response grading for any given participant by the second 
dermatologist will NOT be considered a protocol deviation.  The dermatologists are to be 
blinded to the treatment assignments and must make daily assessment independently (without 
review) of the previous score(s).  The dermatologists identification will be captured on the 
source document.  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.
Table 4.
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:


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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
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.
8.2.6. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in WOCBP at the times listed in the SoA.  
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior the participant’s receiving the study intervention.  Pregnancy tests will also be done 
whenever 1 menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the end of the study.  Pregnancy tests may also be 
repeated if requested by IRBs/ ECs or if required by local regulations.  If a urine test cannot 
be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required.  In
such cases, the participant must be excluded if the serum pregnancy result is positive.
8.2.7. COVID-19 Specific Assessments
Participants will be tested for SARS-CoV-2 infection at the timepoints specified in the SoA.  
Additional testing may be required by local regulations, institutional policies or by the 
Principal Investigator.  The test result must be negative in order for a participant to proceed 
with admission on Day -1.  COVID-19 tests may be conducted at central or local labs.  
COVID-19 specific assessments data will be considered source data.  If the participant has 
had a positive COVID-19 test result, the result of such a test is recorded in the AE section of 
the CRF.


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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days after the last administration of the study intervention.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AE or SAE after the participant has concluded 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has completed the study, and he/she considers the event to be 
reasonably related to the study intervention, the investigator must promptly report the SAE to 
Pfizer using the CT SAE Report Form.


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8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
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/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in 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 towards 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 


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sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental exposure during pregnancy:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion 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.


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
If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
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.


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


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8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
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. Treatment of Overdose
For this study, any dose of study intervention greater than QD or greater than 24 g within a 
24-hour time period 2 hours will be considered an overdose.
Sponsor does not recommend specific treatment for an overdose.


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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 study intervention
(whichever is longer).
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis 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.
8.5. Pharmacokinetics 
Blood samples of approximately 4 mL, to provide approximately 1.2 mL plasma, will be 
collected for measurement of plasma concentrations of PF-07038124 as specified in the SoA.  
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor. The actual date and time (24-hour clock time) of each 
sample will be recorded.
The actual times may change, but the number of samples will remain the same.  All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing.  Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF.  Collection of samples more than 10 hours after dose
administration that are obtained ≤1 hour away from the nominal time relative to dosing will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. This protocol deviation window does not apply to 
samples to be collected more than 10 hours after dose administration at outpatient/follow-up 
visits with visit windows.
The skin around PK sampling must be thoroughly cleansed prior to blood sample collection 
with mild soap and water followed by an isopropyl wipe.
Samples will be used to evaluate the PK of PF-07038124. Samples collected for analyses of 
plasma PF-07038124 concentration may also be used to evaluate safety or efficacy aspects 
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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.
Samples collected for measurement of plasma concentrations of PF-07038124 will be 
analyzed using a validated analytical method in compliance with applicable SOPs.  
 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor.  
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Drug concentration information that would unblind the study will not be reported to 
investigator sites or blinded personnel until the study has been unblinded.
Any changes in the timing or addition of 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/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
 
 
 
 
 
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8.9. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
No statistical hypotheses will be tested in this study.
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9.2. Sample Size Determination
A sample size of 12 participants (4 PF-07038124: 2 vehicle per cohort) has been selected 
empirically to permit adequate characterization of safety, tolerability, skin irritation potential, 
and PK at each dose level in Japanese healthy participants. Participants who discontinue prior 
to completion of the study for non-safety related reasons may be replaced, at the discretion of 
the PI and Sponsor.
9.3. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis 
Set
Description
Enrolled/Randomly 
assigned to study 
intervention
"Enrolled" means a participant’s, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process.  
Potential participants who are screened for the purpose of 
determining eligibility for the study, but do not participate in 
the study, are not considered enrolled, unless otherwise 
specified by the protocol.
Safety
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention.  Participants will 
be analyzed according to the product they actually received.
PK concentration
All participants randomly assigned to study intervention who 
received a dose of PF-07038124 and in whom at least 1 plasma 
sample concentration value is reported.
PK parameter
All participants randomly assigned to study intervention who 
received a dose of PF-07038124 and who have at least 1 of the 
PK parameters of interest calculated.
9.4. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. General Considerations
All analyses described below will be conducted by treatment and cohort.  In addition, data 
from vehicle in Cohort 1 and Cohort 2 will be pooled.
9.4.2. Primary Endpoint(s)
All safety analyses will be performed on the safety analysis set, which is defined as all 
participants randomly assigned to study intervention and who take at least 1 dose of study 


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intervention.  Participants will be analyzed according to the product they actually received.  
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
The primary endpoints of this study are treatment emergent AEs and SAEs, clinically 
significant changes in vital signs, ECG, laboratory tests, and incidence and severity of local 
skin irritation.
The primary endpoints will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and/or graphical presentations in 
order to evaluate the safety, tolerability, and skin irritation potential of PF-07038124.
9.4.2.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTcF interval, PR 
interval, and QRS complex will be summarized by treatment and time.  Changes from 
baseline will be defined as the change between the postdose QTcF value and the predose 
value on Day 1.
The number (%) of participants with maximum postdose QTcF values and maximum 
increases from baseline in the following categories will be tabulated by treatment: 
Safety QTcF Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
9.4.3. Secondary Endpoint(s)
9.4.3.1. Pharmacokinetic Analyses of PF-07038124
PK parameters (AUCtau, and Cmax) for PF-07038124, following multiple-dose topical 
administration, will be derived from the plasma concentration-time profiles using 
noncompartmental methods, as data permit.
The PK parameters to be assessed in this study, their definition, and method of determination 
are listed in Table 5.  Actual PK sampling times will be used in the derivation of PK 
parameters.
No formal inferential statistics will be applied to the PK data.
The plasma PK parameters in Table 5 will be summarized descriptively by treatment group 
in accordance with Pfizer data standards, as data permit.  The plot will include individual 


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participant values and the geometric means for each dose.  These plots will be used to help 
understand the relationship between the PK parameters and dose.
Table 5.
Plasma PK Parameters
Parameter*
Day
Definition
Method of Determination
Cmax
1, 10
Maximum plasma concentration
Observed directly from data
 
AUCtau
1, 10
Area under the plasma 
concentration-time profile from 
time zero to time tau (τ), the dosing 
interval, where tau = 24 hours 
Linear/Log trapezoidal method 
up to (tau), the dosing interval, 
where tau = 24 hours
 
 
 
 
 
 
 
 
 
 
  
 
 
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9.4.6. Other Safety Analyses
AEs, ECGs, BP, pulse rate, temperature, and safety laboratory data will be reviewed and 
summarized on an ongoing basis during the study to evaluate the safety of participants.  Any 
clinical laboratory, ECG, BP, and pulse rate abnormalities of potential clinical concern will 
be described.  Safety data will be presented in tabular and/or graphical format and 
summarized descriptively, where appropriate.
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered source data and will 
not be required to be reported, unless otherwise noted.  However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE.  
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted.  Demographic data collected at screening will be reported.
9.5. Interim Analyses
No interim analyses are planned.
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will not use a DMC. 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the head of the medical institution and reviewed and approved by the IRB/EC 
before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.


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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 to the 
participant and answer all questions regarding the study.  The participant should be given 
sufficient time and opportunity to ask questions and to decide whether or not to participate in 
the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, HIPAA requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant.
Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research.  The optional 
additional research does not require the collection of any further samples. The investigator 
or authorized designee will explain to each participant the objectives of the additional
research. Participants will be told that they are free to refuse to participate and may 


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withdraw their consent at any time and for any reason during the storage period. A separate 
signature will be required to document a participant's agreement to allow specimens to be 
used for additional research. Participants who decline to participate in this optional
additional research will not provide this separate signature.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site will be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations.  In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
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 available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.


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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 (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator or authorized site personnel 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 or authorized site personnel 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 or authorized site personnel 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.


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10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in the study monitoring plan.
Description of the use of computerized system is documented in the Data Management Plan.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.


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Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the SToD system.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 


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problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  For sites other than a Pfizer CRU, the contact number is not intended 
for use by the participant directly, and if a participant calls that number, he or she will be 
directed back to the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol.  Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values.  These additional tests would not require additional collection of 
blood.  Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety issues.
Table 6.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
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

Fibrinogen

hsCRP

Urine drug screeningc

Pregnancy test (-hCG)d

COVID-19 teste
At screening only:

FSHb

Hepatitis B surface antigen

Hepatitis B core antibody

Hepatitis C antibody

Human immunodeficiency 
virus

Syphilis
a.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
b.
For confirmation of postmenopausal status only.
c.
The minimum requirement for drug screening includes cocaine, THC, opiates/opioids, benzodiazepines, 
and amphetamines (others are site and study specific).
d.
Serum or urine -hCG for female participants of childbearing potential per SoA. Serum pregnancy test 
must be performed at screening.
e.
May be conducted at central or local laboratory.
Investigators must document their review of each laboratory safety report.


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


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


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


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occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (and EDP supplemental 
form for EDP)  
Note:  Include all SAEs
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity


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


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


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


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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR

Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3);
OR

Is a WOCBP and using an acceptable contraceptive method as described below 
during the intervention period (for a minimum of 28 days after the last dose of study 
intervention).  The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.


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Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female.

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition, a

High FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 

Female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.*
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.


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5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed.  If not, an additional highly effective 
method of contraception should be used.  The spermatogenesis cycle is 
approximately 90 days.
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation.

Oral;

Intravaginal;*

Transdermal;*

Injectable.*
7. Progestogen-only hormone contraception associated with inhibition of ovulation.

Oral;*

Injectable.*
8. Sexual abstinence.

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.*
10. Male or female* condom with* or without spermicide.
11. Cervical cap*, diaphragm*, or sponge with spermicide*.
12. A combination of male condom with either cervical cap*, diaphragm*, or sponge 
with spermicide* (double-barrier methods).
*) Not approved in Japan


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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI.  
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks.  The increase in TBili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample).  In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased.  This occurrence is still regarded as a 
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).


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


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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as 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).

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (heart 
rate <40 bpm), accelerated idioventricular rhythm (HR >40 bpm to <100 bpm), and 


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monomorphic/polymorphic ventricular tachycardia (HR >100 bpm (such as
torsades de pointes)).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as 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: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
AD
atopic dermatitis
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the curve
AUC24
area under the plasma concentration-time profile from time zero to 
time 24 hours
AUCtau
area under the plasma concentration-time profile from time zero to 
time tau, the dosing interval, where tau = 24 hours
 
AV
atrioventricular
β-hCG
beta-human chorionic gonadotropin
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
cAMP
cyclic adenosine monophosphate
Cav
average concentrations
CFR
Code of Federal Regulations
cGMP
cyclic guanosine monophosphate
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
Cmax
maximum observed concentration
COVID-19
coronavirus disease
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
DMC
data monitoring committee
CCI
CCI
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Abbreviation
Term
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDP
exposure during pregnancy
EFD
embryo-fetal development
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FIH
first-in-human
FSH
follicle-stimulating hormone
fup
fraction unbound in plasma
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HBcAb
hepatitis B core antibody
HBsAg 
hepatitis B surface antigen
HCVAb
hepatitis C antibody
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
hsCRP
high-sensitivity C-reactive protein
IB
investigator’s brochure
IC50
half maximal inhibitory concentration
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IFN
interferon
IL
interleukin
IMP
Investigational Medicinal Product
IND
Investigational New Drug 
INR
international normalized ratio
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IRB
Institutional Review Board
IRT
interactive response technology
IV
intravenous
IWR
interactive Web-based response
JAK
Janus kinase
LBBB
left bundle branch block
LFT
liver function test
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Abbreviation
Term
LPS
lipopolysaccharide
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MRHD
maximum recommended human dose
msec
millisecond
MW
molecular weight
N/A
not applicable
NIMP
Noninvestigational Medicinal Product
NOAEL
no-observed-adverse-effect level
NOEL
no observed effect level
PBMC
peripheral blood mononuclear cells
PDE
phosphodiesterase
PDE4
phosphodiesterase 4
pH
potential of hydrogen
PI
principal investigator
PK
pharmacokinetic(s)
PT
prothrombin time
PVC
premature ventricular contraction/complex
QD
once daily
QoL
quality of life
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
RBC
red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SToD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
t½
terminal phase half-life
Th2
T-Helper 2 Cells
THC
tetrahydrocannabinol
CCI
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CCI
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Abbreviation
Term
TNF
tumor necrosis factor
uCav
unbound average concentrations
ULN
upper limit of normal
US
United States
UVA
ultraviolet A
WBC
white blood cell
WOCBP
woman of childbearing potential
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11. REFERENCES
1.
Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387:1109-22.
2.
Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: 
psychometric validation and responder definition for assessing itch in moderate-to-
severe atopic dermatitis. British Journal of Dermatology. 2019;181:761-9.
3.
Nestle FO, Kaplan DH, Barker J. Psoriasis. New England Journal of Medicine.
2009;361:496-509.
4.
Sbidian E, Chaimani A, Afach S, et al. Systemic pharmacological treatments for chronic 
plaque psoriasis: a network meta‐analysis. Cochrane Database of Systematic Reviews.
2020;(1).
5.
Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a 
novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of 
atopic dermatitis (AD) in children and adults. Journal of the American Academy of 
Dermatology. 2016;75:494-503.e6.
6.
Lebwohl MG, Papp KA, Stein Gold L, et al. Trial of Roflumilast Cream for Chronic 
Plaque Psoriasis. New England Journal of Medicine. 2020;383:229-39.
7.
Draize J H,Woodard G, Calvery H O. Methods for the study of irritation and toxicity of 
substances applied topically to the skin and mucous membranes. Journal of 
Pharmacology and Experimental Therapeutics. 1944:82:377-390.

SAP_001.pdf: 
Protocol C3941003 (PF-07038124) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 1
Protocol C3941003
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, 
PARALLEL COHORT STUDY TO EVALUATE THE SAFETY, TOLERABILITY, 
SKIN IRRITATION POTENTIAL AND PHARMACOKINETICS OF 
MULTIPLE-DOSE, TOPICAL ADMINISTRATION OF PF-07038124 
TO JAPANESE HEALTHY PARTICIPANTS
Statistical Analysis Plan 
(SAP)
Version:
2
Date:
21 Sep 2021


Protocol C3941003 (PF-07038124) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 2
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................3
1. VERSION HISTORY............................................................................................................4
2. INTRODUCTION .................................................................................................................4
2.1. Study Objectives, Endpoints, and Estimands............................................................4
2.1.1. Primary Estimand(s).....................................................................................5
2.1.2. Secondary Estimand(s).................................................................................5
2.1.3. Additional Estimand(s).................................................................................5
2.2. Study Design .............................................................................................................5
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................6
3.1. Primary Endpoint(s) ..................................................................................................6
3.2. Secondary Endpoint(s) ..............................................................................................6
3.4. Baseline Variables.....................................................................................................6
3.5. Safety Endpoints .......................................................................................................6
3.5.1. Adverse Events.............................................................................................6
3.5.2. Laboratory Data............................................................................................7
3.5.3. Vital Signs ....................................................................................................7
3.5.4. Electrocardiograms.......................................................................................7
3.5.5. Skin Irritation Assessment............................................................................8
3.5.6. Other Safety Data .........................................................................................9
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS).....................................................9
5. GENERAL METHODOLOGY AND CONVENTIONS......................................................9
5.1. Hypotheses and Decision Rules ................................................................................9
5.2. General Methods .......................................................................................................9
5.2.1. Analyses for Binary Endpoints.....................................................................9
5.2.2. Analyses for Continuous Endpoints ...........................................................10
5.2.3. Analyses for Categorical Endpoints ...........................................................10
5.2.4. Analyses for Time-to-Event Endpoints ......................................................10
5.3. Methods to Manage Missing Data ..........................................................................10
5.3.1. Standard Safety Data ..................................................................................10
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5.3.2. Skin Irritation Assessment..........................................................................10
5.3.3. Pharmacokinetic Data.................................................................................10
Concentration Below the Limit of Quantification..................................10
Deviations, Missing Concentrations and Anomalous Values ................10
Pharmacokinetic Parameters ..................................................................10
6. ANALYSES AND SUMMARIES ......................................................................................11
6.1. Primary Endpoint(s) ................................................................................................11
6.1.1. Adverse Events...........................................................................................11
6.1.2. Laboratory Data..........................................................................................11
6.1.3. Vital Signs Data..........................................................................................11
6.1.4. Electrocardiograms.....................................................................................12
6.1.5. Skin Irritation Assessment..........................................................................12
6.2. Secondary Endpoint(s) ............................................................................................13
6.2.1. Pharmacokinetic Parameters.......................................................................13
6.4. Subset Analyses.......................................................................................................14
6.5. Baseline and Other Summaries and Analyses.........................................................15
6.5.1. Baseline Summaries....................................................................................15
6.5.2. Study Conduct and Participant Disposition................................................15
6.5.3. Concomitant Medications and Nondrug Treatments..................................15
6.6. Safety Summaries and Analyses .............................................................................15
7. INTERIM ANALYSES.......................................................................................................15
8. REFERENCES ....................................................................................................................15
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................4
Table 2.
Skin Irritation Assessment Using Draize Scoring ......................................8
Table 3.
PK Parameters to be Summarized Decsriptively......................................13
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1. VERSION HISTORY
Table 1.
Summary of Changes
Version/
Date
Associated
Protocol 
Amendment
Rationale
Specific Changes
1
10 Mar 2021
Original 
08 Jan 2021
N/A
N/A
2
21 Sep 2021
Amendment 1
12 Mar 2021
Clarification 
and addition of 
analyses
•
Added plots of vital signs data (section 
6.1.3)
•
Added plots of ECG data (section 6.1.4)
•
Clarified analyses of skin irritation 
assessment (section 6.1.5)
•
Added categorical class for QT of 
potential clinical concern to align with 
section 6.1.4 (appendix 1)
2. INTRODUCTION
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C3941003.  This document may modify the 
plans outlined in the protocol; however, any major modifications of the primary endpoint 
definition or its analysis will also be reflected in a protocol amendment.
2.1. Study Objectives, Endpoints, and Estimands
The followings are objectives and endpoints in this study.  Estimand framework is not 
applied to this phase 1 study.
Objectives
Endpoints
Primary: 
Primary: 
•
To evaluate the safety, tolerability, and skin 
irritation potential of PF-07038124, following 
multiple doses applied topically, in Japanese 
healthy participants.
•
Incidence of treatment emergent AEs and SAEs, 
clinically significant changes in vital signs, 
ECG, and laboratory tests during the entire 
study.
•
Incidence and severity of local skin irritation at 
times indicated in SoA.
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Secondary: 
Secondary: 
•
To characterize the PK of PF-07038124, 
following topical administration, in Japanese 
healthy participants.
•
PF-07038124 PK parameters following topical 
application on Days 1 and 10, as data permit: 
AUCtau, and Cmax, if applicable.
 
 
 
 
 
 
 
 
 
2.1.1. Primary Estimand(s)
Not applicable.
2.1.2. Secondary Estimand(s)
Not applicable.
2.1.3. Additional Estimand(s)
Not applicable.
2.2. Study Design
This is a Phase 1, randomized, double-blind, vehicle-controlled, parallel cohort study to 
evaluate the safety, tolerability, skin irritation potential, and PK of PF-07038124 in Japanese 
healthy adult participants. Both cohorts can be conducted simultaneously.
This study will evaluate the safety, tolerability, skin irritation potential and PK following 
application of PF-07038124 at 0.01% concentration and vehicle to 2000 cm2 (Cohort 1; 
approximately 10% BSA) or 4000 cm2 (Cohort 2; approximately 20% BSA).
Participants will be randomized to receive PF-07038124 or vehicle in a ratio of 
4 PF-07038124: 2 vehicle, per cohort. Each participant will receive multiple doses of 
PF-07038124 or vehicle starting on Day 1 topically applied for 10 consecutive days; applied 
QD in the AM for Cohort 1 and Cohort 2.  Participants will not be randomly assigned to 
cohort.  The first group of participants will be enrolled Cohort 1 followed by Cohort 2.  All 
participants will have the study interventions randomly assigned, for the purpose of 
determining skin irritation potential, as well as PK, safety and tolerability. 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.
The total participation time for each participant is approximately 66 days, including the 
screening period of up to 28 days, the double-blind treatment period of 10 days, and the 
follow-up period of 28 days from last dose of the study intervention.
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Approximately 12 Japanese healthy adult participants are planned to participate in this study.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
Primary endpoints are:
•
Incidence of treatment emergent AEs and SAEs, clinically significant changes in vital 
signs, ECG, and laboratory tests during the entire study;
•
Incidence and severity of local skin irritation at times indicated in SoA.
3.2. Secondary Endpoint(s)
Secondary endpoints are:
•
PF-07038124 PK parameters following topical application on Days 1 and 10, as data 
permit: AUCtau, and Cmax, if applicable.
 
 
3.4. Baseline Variables
There are no baseline variables used as covariates or stratification factors in this study.
The demographic and baseline characteristics data will include age, sex, ethnicity, race, 
weight, height, body mass index.  Baseline variables are those collected on Day 1 prior to 
dosing or last measurement during screening visits before Day 1.
3.5. Safety Endpoints
3.5.1. Adverse Events
An adverse event is considered treatment emergent relative to a given treatment if:
•
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.
The effective duration of treatment is determined by the lag time.  The CDISC and Pfizer 
Standard (CaPS) default treatment LAG of 365 days post last dose of study drug will be used 
for this study.
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3.5.2. Laboratory Data
Safety laboratory tests will be performed as described in the protocol.
To determine if there are any clinically significant laboratory abnormalities, the 
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 participant’s baseline test result is within or outside the laboratory 
reference range for the particular laboratory parameter.
Baseline will be the last predose measurement.
3.5.3. Vital Signs
Supine blood pressure and pulse measurements will be taken at all time points listed in the 
Schedule of Activities given in the protocol.
Baseline will be defined as the last predose recording.
The following vital signs endpoints will be determined:

The maximum decrease and increase from baseline over all measurements taken postdose 
for supine systolic and diastolic blood pressures;

The maximum decrease and increase from baseline over all measurements taken postdose 
for supine pulse rate.
The maximum increase from baseline will be calculated by first subtracting the baseline 
value from each postdose measurement to give the change from baseline.  The maximum of 
these values over the treatment period will then be selected, except in the case where a 
participant does not show an increase.  In such an instance, the minimum decrease should be 
taken.
Similarly, the maximum decrease from baseline will be determined by selecting the 
minimum value of the change from baseline.  In cases where a participant does not show a 
decrease, the minimum increase should be taken.
3.5.4. Electrocardiograms
Standard 12-lead ECGs will be taken at all time points listed in the Schedule of Activities 
given in the protocol.
Baseline will be defined as the single supine 12-lead ECGs predose recording.
The QT, QTcF, PR, QRS and heart rate will be recorded at each assessment time.
If not supplied, QTcF will be derived using Fridericia’s heart rate correction formula:
QTcF = QT / (RR)1/3
where RR = 60/HR (if not provided)


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The maximum absolute value (postdose) and the maximum increase from baseline will be 
determined over all measurements taken postdose for QTcF, QT, heart rate, PR and QRS.
The maximum increase from baseline will be calculated by first subtracting the baseline 
value from each postdose measurement to give the change from baseline.  The maximum of 
these values over the treatment period will then be selected, except in the case where a 
participant does not show an increase.  In such an instance, the minimum decrease should be 
taken.
3.5.5. Skin Irritation Assessment
Local toleration will be assessed by Draize scoring and clinical observation in Table 2.
All numerical, letter grades, and superficial observations will be collected on the designated 
CRF.
Table 2.
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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3.5.6. Other Safety Data
Additional safety data, body temperature, fibrinogen and hsCRP will be colledted as
described in the protocol and will be listed (if collected in the sponsor’s database).
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.
Participant Analysis 
Set
Description
Enrolled/Randomly 
assigned to study 
intervention 
"Enrolled" means a participant’s, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process.  
Potential participants who are screened for the purpose of 
determining eligibility for the study, but do not participate in 
the study, are not considered enrolled, unless otherwise 
specified by the protocol.
Safety
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention.  Participants 
will be analyzed according to the product they actually 
received.
PK concentration
All participants randomly assigned to study intervention who 
received a dose of PF-07038124 and in whom at least 1 
plasma sample concentration value is reported.
PK parameter
All participants randomly assigned to study intervention who 
received a dose of PF-07038124 and who have at least 1 of 
the PK parameters of interest calculated.
5. GENERAL METHODOLOGY AND CONVENTIONS
This is a double-blind study.  Final analysis will follow the official database release.
5.1. Hypotheses and Decision Rules
There are no statistical hypotheses or decision rules.
5.2. General Methods
5.2.1. Analyses for Binary Endpoints
Binary endpoints will be summarized by treatment and visit (if appropriate) with number and 
percentage of participants in each category, if not otherwise specified.


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5.2.2. Analyses for Continuous Endpoints
Continuous endpoints will be summarized by treatment and visit (if appropriate) using 
descriptive statistics, including n, arithmetic mean, median, standard deviation (SD), 
minimum and maximum will be used to summarize the endpoints, if not otherwise specified.
5.2.3. Analyses for Categorical Endpoints
Categorical endpoints will be summarized by treatment and visit (if appropriate) with number 
and percent of participants in the treatment group within each category, if not otherwise 
specified.
5.2.4. Analyses for Time-to-Event Endpoints
There are no time-to-event endpoints in this study.
5.3. Methods to Manage Missing Data
5.3.1. Standard Safety Data
For the analysis of standard safety data (i.e., all safety data except local skin irritation), the 
sponsor data standard rules for imputation will be applied.
5.3.2. Skin Irritation Assessment
Missing values will not be imputed.
5.3.3. Pharmacokinetic Data
Concentration 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, plots of mean profiles and plots of median profiles, summary statistics 
will be calculated setting concentrations to missing if one of the following cases is true:
1. A concentration has been collected as ND (i.e., not done) or NS (i.e., no sample);
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
(>50%) of the data are missing.
Pharmacokinetic Parameters
Actual PK sampling times will be used in the derivation of PK parameters.


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If a PK parameter cannot be derived from a participant’s concentration data, the parameter 
will be coded as NC (i.e., not calculated).  (Note that NC values will not be generated beyond
the day that a participant discontinues.)
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular dose with ≥3 evaluable measurements.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to an unexpected event), this will be footnoted in summary tables and will not be included in 
the calculation of summary statistics.
6. ANALYSES AND SUMMARIES
All analyses described below will be conducted by treatment and cohort.  In addition, data 
from vehicle in Cohort 1 and Cohort 2 will be pooled.
6.1. Primary Endpoint(s)
The primary endpoints of this study are the standard safety endpoints and local skin irritation
presented in the Section 3.1.  A set of summary tables split by cohort and treatment group 
(including pooled vehicle group) will be produced to evaluate potential risk associated with 
the safety and toleration of administering PF-07038124.
No formal analyses are planned safety data.  The safety endpoints will be listed and 
summarized in accordance with the sponsor reporting standards, where the resulting data 
presentations will consist of participants from the safety analysis set.
6.1.1. Adverse Events
Adverse events will be listed and summarized in accordance with the sponsor reporting 
standards.
6.1.2. Laboratory Data
Laboratory data will be listed and summarized in accordance with the sponsor reporting 
standards.  Baseline is as defined in Section 3.5.2.
6.1.3. Vital Signs Data
Absolute values and changes from baseline in supine systolic and diastolic blood pressure 
and pulse rate will be summarized by cohort, treatment group and postdose timepoints, 
according to the sponsor reporting standards.  Tables will be paged by parameter.  Baseline is 
as defined in Section 3.5.3.
Mean changes from baseline for systolic and diastolic blood pressure and pulse rate will be 
plotted against time postdose.  On each plot there will be 1 line for each treatment.  Data 
from all cohorts will be plotted on the same figure using separate lines for the 2 vehicles.  
Corresponding individual plots of change from baseline will also be produced for each cohort 
and treatment.


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Maximum absolute values and changes from baseline for vital signs will also be summarized 
descriptively by treatment and cohort using categories as defined in Appendix 1.  Numbers 
and percentages of participants meeting categorical criteria will be provided.  All planned 
and unplanned postdose timepoints will be counted in these categorical summaries.  All 
values meeting the criteria of potential clinical concern will be listed.
If necessary, maximum increases or decreases in vital signs may be summarized in addition 
to the above.
6.1.4. Electrocardiograms
Absolute values and changes from baseline in QT, heart rate, QTcF, PR and QRS will be 
summarized by cohort, treatment group and postdose timepoints.  Baseline is as defined in 
Section 3.5.4. Tables will be paged by parameter.
Mean changes from baseline in QT, heart rate, QTcF, PR and QRS will be plotted against 
time postdose.  On each plot there will be 1 line for each treatment.  Data from all cohorts 
will be plotted on the same figure using separate lines for the 2 vehicles.  Corresponding 
individual plots of change from baseline will also be produced for each cohort and treatment.
Changes from baseline in QTcF will also be plotted separately against PF-07038124
concentrations.  This will be a scatter plot for all observations where QTcF and PF-07038124 
concentration are recorded.  Vehicle data will also be included (with drug concentration set 
to zero).  Data from all cohorts will be plotted on the same figure.  Different symbols will be 
used for each treatment.  
The number (%) of participants with maximum postdose QTcF values and maximum 
increases from baseline in the following categories will be tabulated by cohort and treatment
group:
Safety QTcF Assessment
Degree of 
Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
6.1.5. Skin Irritation Assessment
Draize numerical grades, letter grades and superficial observations will be summarized by 
visit and assessment location (i.e., back, leg, arm, abdomen and chest).  If there are multiple 
observations of numerical score in an assessment location (e.g., right arm and left arm), 
maximum score regardless of body side and directionality will be used.  Similarly, if  there 
are multiple observations of letter grades or superficial observations, “Y” will be used in 


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preference to “N” for summarization. For numerical grades, the followings will also be 
summarized:
•
Maximum score by visit, regardless of assessment location;
•
Maximum score during the study, regardless of visit and assessment location.
6.2. Secondary Endpoint(s)
6.2.1. Pharmacokinetic Parameters
PK parameters (AUCtau and Cmax) will be listed, summarized and plotted for participants in 
the PK parameter analysis set (as defined in Section 4).  Missing values will be handled as 
detailed in Section 5.3.3.  Each PK parameter will be summarized by day and treatment 
group, 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, Cmax
n, arithmetic mean, median, SD, minimum, maximum, 
percent coefficient of variation (%CV), geometric mean and 
geometric %CV
There will be one summary table presenting all PK parameters.
AUCtau and Cmax will be plotted against treatment group, and will include individual 
participant values and geometric means for each treatment group. The plots will be paged by 
day. Geometric means will have a different symbol than individual values.  A footnote will 
be added to the plots to indicate that geometric means are presented.
 
 
 
 
 
 
 
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6.4. Subset Analyses
No subset analysis will be conducted for this study.
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6.5. Baseline and Other Summaries and Analyses
6.5.1. Baseline Summaries
Demographic and baseline characteristics (age, gender, race, ethnicity, weight, height and 
body mass index) collected prior to the first dose of the study drug will be summarized in 
accordance with the sponsor reporting standards.
6.5.2. Study Conduct and Participant Disposition
The following participant dispositions will be reported following the sponsor reporting 
standards:

A summary of participant discontinuations up to the end of study;

Summary of participant dispositions analysed for PK and safety;

Summary of numbers of participant treated by treatment group.
6.5.3. Concomitant Medications and Nondrug Treatments
All concomitant medications as well as nondrug treatments will be provided in the listings.
6.6. Safety Summaries and Analyses
The details of safety analyses are described in the Section 6.1.
7. INTERIM ANALYSES
No interim analyses are planned.
8. REFERENCES
None.


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Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern
CATEGORIES FOR QTCF
QTcF (ms)
450≤ max. <480
480≤ max.<500
max. ≥500
QTcF (ms) 
increase from 
baseline
30≤ max. <60
max. ≥60
CATEGORIES FOR QT
QT (ms)
max. ≥500
CATEGORIES FOR PR AND QRS
PR (ms)
max. ≥300
PR (ms) increase 
from baseline
Baseline >200 
and max. 
≥25% increase
Baseline ≤200 
and max. 
≥50% increase
QRS (ms)
max. ≥140
QRS (ms) 
increase from 
baseline
≥50% increase
CATEGORIES FOR VITAL SIGNS
Systolic BP (mm Hg)
min. <90
Systolic BP (mm Hg) 
change from baseline
max. decrease ≥30
max. increase ≥30
Diastolic BP (mm Hg)
min. <50
Diastolic BP (mm Hg) 
change from baseline
max. decrease ≥20
max. increase ≥20
Supine pulse rate (bpm)
min. <40
max. >120
Standing pulse rate (bpm)
min. <40
max. >140
Measurements that fulfill these criteria are to be listed in report.