Clinical trial NCT04903093
Conditions: Healthy Volunteers
Keywords: Abrocitinib Atopic Dermatitis Healthy Volunteers Relative Bioavailability Taste Assessment
Sponsor: Pfizer
Start date: 2021-06-04; Completion date: 2021-10-26
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This study consists of 2 parts: Part A is to estimate the relative bioavailability of a single 200 mg dose of abrocitinib oral suspension (Test formulation) compared to the commercial abrocitinib tablet (200 mg) (Reference formulation). The effect of an acid-reducing agent on the pharmacokinetics of abrocitinib and its metabolites will also be evaluated by administering abrocitinib 200 mg commercial tablet with or without famotidine 40 mg, as an acid-reducing agent. Part B is to assess the taste and palatability of six different abrocitinib oral suspension formulations. Additionally, the safety and tolerability of abrocitinib tablet (in Part A) and abrocitinib oral suspension formulations (in Part B) will be assessed when given with or without famotidine 40 mg once daily.

Detailed description:
This is a Phase 1 randomized study in healthy participants to estimate the relative bioavailability of abrocitinib oral suspension (Test formulation) compared to commercial abrocitinib tablet (Reference formulation) under fasted condition. The effect of an acid-reducing agent on the pharmacokinetics of the commercial tablet formulation will be evaluated by administering abrocitinib 200 mg commercial tablet with famotidine 40 mg, as an acid-reducing agent. Assessment of taste and palatability of six different abrocitinib suspension formulations will also be performed. This study consists of 2 parts, as listed below:

Part A

Part A of the study will be an open label, randomized, single dose, crossover, 3-treatment, 6 sequence, 3-period design in healthy male and/or female adult participants (18-55 years). Healthy participants will be screened within 28 days prior to the first administration of the study intervention to confirm that they meet the participant selection criteria for the study. Eligible participants will be admitted to the CRU on Day -1 and will be confined in the CRU until discharge, on Day 2 of Period 9 in Part B, after completing both Parts A and B of the study. In Part A, participants will be randomized to receive one of the following: a single 200 mg dose of abrocitinib commercial tablet (Treatment A), a single 200 mg dose of abrocitinib oral suspension formulation 1 (Treatment B), or famotidine (40 mg) administered 120 minutes before a single 200 mg dose of abrocitinib commercial tablet (Treatment C). All participants will be fasting for at least 10 hours before taking abrocitinib.

Part B

Part B will be a single-blind, randomized, 6-period, crossover study in healthy male and/or female adult participants (18-55 years). For any new healthy participants joining Part B only, screening will be performed within 28 days prior to the first administration of the study intervention to confirm that they meet the participant selection criteria for the study. New participants enrolled in Part B only will be admitted to the CRU on Day -1 and will be confined in the CRU until discharge, which is Day 2 of Period 9. On Day 1 of each treatment period under fasted conditions, participants will receive a famotidine tablet (40 mg with 240 mL of room temperature water) administered 120 minutes before a single 200 mg dose of abrocitinib oral suspensions (Formulations 1 to 6) or administered a single 200 mg dose of abrocitinib oral suspension alone (Formulations 1 to 6), after a fast of at least 10 hours before abrocitinib administration.

Arms: arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None arm 7: None arm 8: None arm 9: None arm 10: None arm 11: None arm 12: None arm 13: None arm 14: None arm 15: None
Interventions: intervention 1: Abrocitinib tablet intervention 2: Abrocitinib Suspension F1 intervention 3: Abrocitinib Suspension F2 intervention 4: Abrocitinib Suspension F3 intervention 5: Abrocitinib Suspension F4 intervention 6: Abrocitinib Suspension F5 intervention 7: Abrocitinib Suspension F6 intervention 8: Famotidine
Intervention descriptions: intervention 1: Single dose of abrocitinib 200 mg tablet will be administered after an overnight fast of at least 10 hours. intervention 2: Single dose of abrocitinib 200 mg oral suspension formulation 1 will be administered after an overnight fast of at least 10 hours. intervention 3: Single dose of abrocitinib 200 mg oral suspension formulation 2 will be administered after an overnight fast of at least 10 hours. intervention 4: Single dose of abrocitinib 200 mg oral suspension formulation 3 will be administered after an overnight fast of at least 10 hours. intervention 5: Single dose of abrocitinib 200 mg oral suspension formulation 4 will be administered after an overnight fast of at least 10 hours. intervention 6: Single dose of abrocitinib 200 mg oral suspension formulation 5 will be administered after an overnight fast of at least 10 hours. intervention 7: Single dose of abrocitinib 200 mg oral suspension formulation 6 will be administered after an overnight fast of at least 10 hours. intervention 8: Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.

Protocol documents:
Prot_000.pdf: 
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A PHASE 1, RANDOMIZED, CROSSOVER STUDY TO EVALUATE RELATIVE 
BIOAVAILABILITY OF ABROCITINIB ORAL SUSPENSION AND EFFECT OF 
AN ACID-REDUCING AGENT ON THE BIOAVAILABILITY OF ABROCITINIB
COMMERCIAL TABLET AND TO ASSESS THE TASTE OF ABROCITINIB ORAL 
FORMULATIONS IN HEALTHY ADULT PARTICIPANTS AGED 18 TO 55 YEARS
OF AGE
Study Intervention Number:
PF-04965842
Study Intervention Name:
Abrocitinib
US IND Number:
EudraCT Number:
N/A
Protocol Number:
B7451061
Phase:
1
Brief Title: A Phase 1 Study Evaluating Relative Bioavailability of an Oral Suspension 
of Abrocitinib and Effect of an Acid-Reducing Agent on the Bioavailability of 
Abrocitinib and Assessing the Taste of Abrocitinib Oral Formulations in Healthy Adult 
Participants Aged 18 to 55 Years of Age.
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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Document History
Document
Version Date
Original protocol
06 May 2021


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
LIST OF FIGURES ...................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................14
1.3. Schedule of Activities .............................................................................................15
2. INTRODUCTION ...............................................................................................................20
2.1. Study Rationale .......................................................................................................20
2.2. Background .............................................................................................................20
2.2.1. Mechanism of Action/Indication................................................................20
2.2.2. Overview of Disease State..........................................................................21
2.2.3. Rationale for Development of Abrocitinib.................................................21
2.2.4. Nonclinical Pharmacology..........................................................................22
2.2.5. Nonclinical Pharmacokinetics and Metabolism .........................................23
2.2.6. Nonclinical Safety ......................................................................................23
2.2.7. Clinical Overview.......................................................................................24
2.2.7.1. Summary of Safety Data from Completed Studies ...................24
2.2.7.2. Summary of Abrocitinib Pharmacokinetics, Metabolism 
and In Vitro Enzymology..................................................................26
2.3. Benefit/Risk Assessment.........................................................................................28
3. OBJECTIVES AND ENDPOINTS.....................................................................................29
4. STUDY DESIGN.................................................................................................................29
4.1. Overall Design.........................................................................................................29
4.2. Scientific Rationale for Study Design.....................................................................32
4.2.1. Choice of Contraception/Barrier Requirements .........................................34
4.2.2. Collection of Retained Research Samples..................................................34
4.3. Justification for Dose ..............................................................................................34
4.4. End of Study Definition ..........................................................................................35
5. STUDY POPULATION......................................................................................................35
5.1. Inclusion Criteria.....................................................................................................35
5.2. Exclusion Criteria....................................................................................................37


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5.3. Lifestyle Considerations..........................................................................................40
5.3.1. Meals and Dietary Restrictions...................................................................40
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................40
5.3.3. Activity .......................................................................................................40
5.3.4. Contraception..............................................................................................41
5.4. Screen Failures ........................................................................................................41
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................41
6.1. Study Intervention(s) Administered........................................................................41
6.1.1. Administration............................................................................................44
6.2. Preparation, Handling, Storage, and Accountability...............................................44
6.2.1. Preparation and Dispensing........................................................................45
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................46
6.3.1. Allocation to Study Intervention ................................................................46
6.4. Study Intervention Compliance...............................................................................46
6.5. Dose Modification...................................................................................................46
6.6. Continued Access to Study Intervention After the End of the Study......................46
6.7. Treatment of Overdose............................................................................................46
6.8. Concomitant Therapy..............................................................................................47
6.8.1. Rescue Medicine.........................................................................................48
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................48
7.1. Discontinuation of Study Intervention ....................................................................48
7.2. Participant Discontinuation/Withdrawal From the Study.......................................48
7.2.1. Withdrawal of Consent...............................................................................49
7.3. Lost to Follow-up....................................................................................................49
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................49
8.1. Efficacy Assessments..............................................................................................51
8.2. Safety Assessments .................................................................................................51
8.2.1. Physical Examinations................................................................................51
8.2.2. Vital Signs ..................................................................................................51
8.2.2.1. Temperature ..............................................................................52
8.2.3. Electrocardiograms.....................................................................................52


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8.2.4. Clinical Safety Laboratory Assessments ....................................................53
8.2.5. COVID-19 Specific Assessments...............................................................53
8.2.6. Pregnancy Testing ......................................................................................53
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................54
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......54
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................55
8.3.1.2. Recording Nonserious AEs and SAEs on the DCT ..................55
8.3.2. Method of Detecting AEs and SAEs ..........................................................55
8.3.3. Follow-Up of AEs and SAEs......................................................................55
8.3.4. Regulatory Reporting Requirements for SAEs...........................................56
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................56
8.3.5.1. Exposure During Pregnancy......................................................56
8.3.5.2. Exposure During Breastfeeding ................................................58
8.3.5.3. Occupational Exposure .............................................................58
8.3.6. Cardiovascular and Death Events...............................................................58
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................59
8.3.8. Adverse Events of Special Interest.............................................................59
8.3.8.1. Lack of Efficacy........................................................................59
8.3.9. Medical Device Deficiencies......................................................................59
8.3.10. Medication Errors.....................................................................................59
8.4. Pharmacokinetics ....................................................................................................60
8.4.1. Plasma for Analysis of Abrocitinib and Metabolites..................................60
8.6. Biomarkers ..............................................................................................................62
8.7. Immunogenicity Assessments.................................................................................62
8.8. Health Economics ...................................................................................................62
9. STATISTICAL CONSIDERATIONS ................................................................................62
9.1. Statistical Hypotheses .............................................................................................62
9.2. Analysis Sets ...........................................................................................................63
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9.3. Statistical Analyses .................................................................................................63
9.3.1. Safety Analyses ..........................................................................................63
9.3.1.1. Electrocardiogram Analyses......................................................64
9.4. Interim Analyses .....................................................................................................66
10. SUPPORTING DOCUMENTS AND OPERATIONAL CONSIDERATIONS...............68
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............68
10.1.1. Regulatory and Ethical Considerations ....................................................68
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................69
10.1.2. Informed Consent Process ........................................................................69
10.1.3. Data Protection .........................................................................................70
10.1.4. Committees Structure ...............................................................................70
10.1.4.1. Data Monitoring Committee ...................................................70
10.1.5. Dissemination of Clinical Study Data ......................................................71
10.1.6. Data Quality Assurance ............................................................................72
10.1.7. Source Documents....................................................................................73
10.1.8. Study and Site Start and Closure ..............................................................73
10.1.9. Publication Policy.....................................................................................74
10.1.10. Sponsor’s Qualified Medical Personnel .................................................75
10.2. Appendix 2: Clinical Laboratory Tests .................................................................76
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................79
10.3.1. Definition of AE .......................................................................................79
10.3.2. Definition of an SAE ................................................................................80
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................81
10.3.4. Reporting of SAEs....................................................................................85
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information................................................................................................................86
10.4.1. Male Participant Reproductive Inclusion Criteria....................................86
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10.4.2. Female Participant Reproductive Inclusion Criteria.................................86
10.4.3. Woman of Childbearing Potential ............................................................86
10.4.4. Contraception Methods.............................................................................87
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .......90
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................92
10.8. Appendix 8: Taste Assessment Questionnaire......................................................94
10.9. Appendix 9: Abbreviations .................................................................................103
11. REFERENCES ................................................................................................................107
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LIST OF TABLES
Table 1.
Schedule of Activities (Part A)................................................................15
Table 2.
Schedule of Activities (Part B).................................................................17
Table 4.
Randomized Treatment Sequences of Part A ...........................................30
Table 5.
Randomized Treatment Sequences of Part B ...........................................31
Table 6.
Summary of Abrocitinib Oral Suspension Formulations to be 
administered for PK and Taste Assessment..............................................43
Table 7.
Safety QTc Assessment ............................................................................64
Table 8.
Derivation of PK Parameters....................................................................65
Table 9.
Width of 90% CIs for Different Estimated Effects of 
Test/Reference Ratio ................................................................................66
Table 10.
Half width of a two-sided 90% CI of the estimated mean for each of 
the taste assessment questions, with 80% coverage probability...............67
Table 12.
Protocol-Required Safety Laboratory Assessments .................................77
LIST OF FIGURES
Figure 1.
Abrocitinib pH Solubility Curve ..............................................................34
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Brief Title: A Phase 1 Study Evaluating Relative Bioavailability of an Oral Suspension of 
Abrocitinib and Effect of an Acid-Reducing Agent on the Bioavailability of Abrocitinib and
Assessing the Taste of Abrocitinib Oral Formulations in Healthy Adult Participants Aged 18 
to 55 Years of Age.
Rationale
PF-04965842 (abrocitinib) is a JAK 1 inhibitor that is developed for the treatment of AD. 
Key cytokines implicated in the pathophysiology of AD including IL-4, IL-5, IL-13, IL-22, 
IL-31, and IFN-γ, require JAK1 for signal transduction, suggesting that selective JAK1 
inhibitors, that modulate the activity of these cytokines, represent a compelling approach to 
the treatment of inflammatory skin diseases such as AD. Abrocitinib is being developed as an 
oral treatment for participants with moderate to severe AD based on its mechanism of action, 
and the clinical results obtained in Phase 1 and Phase 2 studies.
Abrocitinib pediatric program will be initiated to fulfill the regulatory requirements. Critical 
to the regulatory requirements is the development and filing of a pediatric age-appropriate 
formulation for AD participants aged 6 months to <12 years, with rBA similar to currently 
developed abrocitinib commercial tablet and with acceptable palatability. Thus, this study 
will be conducted to estimate the rBA of an oral suspension formulation of abrocitinib 
compared to abrocitinib commercial tablet. The potential effects of alterations in 
gastrointestinal pH induced by an ARA on the PK of abrocitinib commercial tablet and its 
major metabolite are also evaluated in this study. A taste evaluation will also be conducted to 
assess the taste and palatability of six different oral suspension formulations for abrocitinib. 
The results of this taste assessment will help in guiding the selection and development of 
abrocitinib pediatrics formulation and inform whether taste masking is required for the 
commercial pediatric formulation.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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As described above, this study consists of 2 parts: Part A is to estimate the rBA of a single 
200 mg dose of abrocitinib oral suspension compared to the commercial abrocitinib 
tablet (200 mg). The effect of ARA on the BA of abrocitinib and its metabolites will also be
evaluated by administering abrocitinib 200 mg commercial tablet with or without famotidine 
40 mg, as an ARA. Part B is to assess the taste and palatability of six different abrocitinib 
oral suspension formulations, to guide the selection and development of abrocitinib pediatrics 
formulation.
 
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Objectives and Endpoints
Objectives
Endpoints
Primary: 
Primary: 
Part A:
•
Estimate the rBA of abrocitinib 200 mg oral 
suspension formulation 1 compared to the 
1×200 mg of abrocitinib commercial tablet 
under fasting condition.
•
Evaluate the effect of a single dose of an acid-
reducing agent (famotidine 40 mg) on the BA
of abrocitinib 1×200 mg commercial tablet 
under fasting conditions.
•
Plasma abrocitinib PK parameters: AUCinf (if 
data permit), AUClast and Cmax after 
administration of abrocitinib oral suspension 
formulation and commercial tablet.
•
Plasma abrocitinib PK parameters: AUCinf (if 
data permit), AUClast and Cmax after 
administration of ARA plus abrocitinib 
commercial tablet.
Part B:
•
Evaluate the taste and palatability of 
6 abrocitinib suspension formulations using a 
200 mg dose.
•
Taste Assessment Survey Scoring Metrics after 
suspension formulation: mouthfeel, bitterness, 
tongue/mouth burn, saltiness, sourness, and 
overall liking.
Secondary: 
Secondary: 
 
 
•
Determine the PK of metabolites (M1, M2 and 
M4) following the administration of 1×200 mg 
of abrocitinib commercial tablet with or without
an ARA (famotidine 40 mg) in Part A.
•
Evaluate the safety and tolerability following 
oral administration of each of the abrocitinib 
formulations in Parts A and B.
•
PK parameters: AUCinf (if data permit), AUClast
and Cmax after administration of 1×200 mg of
abrocitinib commercial tablet with or without an 
ARA.
•
Assessment of TEAEs, clinical laboratory tests, 
vital signs, and 12-lead ECGs.
 
 
 
 
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Overall Design
Brief Summary
This is a Phase 1 randomized, crossover study in healthy participants to estimate the rBA of 
abrocitinib oral suspension (Test formulation) compared to commercial abrocitinib tablet
(Reference formulation) under fasted condition. The effect of ARA on the BA of the 
commercial tablet formulation will be evaluated by administering abrocitinib 200 mg 
commercial tablet with famotidine 40 mg as an ARA. Assessment of taste and palatability of 
six different abrocitinib suspensions will also be performed to guide the selection and 
development of abrocitinib pediatrics oral suspension formulation. This study consists of 
2 parts, as listed below.
Part A: 
Part A of the study will be an open label, randomized, single dose, crossover, 3-treatment, 
6 -sequence, 3-period design in healthy male and/or female adult participants (18-55 years). 
Healthy participants will be screened within 28 days prior to the first administration of the 
study intervention to confirm that they meet the participant selection criteria for the study. 
Eligible participants will be admitted to the CRU on Day -1 and will be confined in the CRU 
until discharge, on Day 2 of Period 9 in Part B, after completing both Parts A and B of the 
study. In Part A, participants will be randomized to receive one of the following: a single 
200 mg dose of abrocitinib commercial tablet (Treatment A), a single 200 mg dose of 
abrocitinib oral suspension formulation 1 (Treatment B), or famotidine (40 mg) administered 
120 minutes before a single 200 mg dose of abrocitinib commercial tablet (Treatment C). All 
participants will be fasting for at least 10 hours before taking abrocitinib.
Part B: 
Participants who complete Part A of the study are expected to proceed to Part B. Part B will 
be a single-blind, randomized, 6-period, crossover study in healthy male and/or female adult 
participants (18-55 years). For any new healthy participants joining Part B only to support 
the achievement of the required number of healthy participants enrolled and randomized in 
this part of the study, screening will be performed within 28 days prior to the first 
administration of the study intervention to confirm that they meet the participant selection 
criteria for the study. New participants enrolled in Part B only will be admitted to the CRU 
on Day -1 and will be confined in the CRU until discharge, which is Day 2 of Period 9. On 
Day 1 of each treatment period under fasted conditions, participants will receive a famotidine 
tablet (40 mg with 240 mL of room temperature water) administered 120 minutes before a 
single 200 mg dose of abrocitinib oral suspensions (Formulations 1 to 6) or administered a 
single 200 mg dose of abrocitinib oral suspension alone (Formulations 1 to 6), after a fast of 
at least 10 hours before abrocitinib administration. 
Number of Participants
In Parts A and B of the study, approximately 18 participants will be randomly assigned to 
study intervention (1 of 6 sequences).


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Intervention Groups and Duration
Part A:
Each randomized treatment sequence will consist of 3 treatment periods.
Randomized Treatment Sequences of Part A
Sequence
Period 1
Period 2
Period 3
1 (n=3)
A
B
C
2 (n=3)
B
C
A
3 (n=3)
C
A
B
4 (n=3)
A
C
B
5 (n=3)
B
A
C
6 (n=3)
C
B
A
Treatment A = Abrocitinib 200 mg commercial tablet only, under fasted conditions.
Treatment B = Abrocitinib 200 mg oral suspension formulation 1 only, under fasted conditions.
Treatment C = Famotidine 40 mg tablet administered 2 hours prior to abrocitinib 200 mg commercial tablet 
under fasted conditions.
Part B:
Each randomized treatment sequence will consist of 6 treatment periods.
Randomized Treatment Sequences of Part B
Sequence
Period 4
Period 5
Period 6
Period 7
Period 8
Period 9
1 (n=3)
F1+ARA
F2+ARA
F3+ARA
F4+ARA
F5+ARA
F6+ARA
2 (n=3)
F6+ARA
F1+ARA
F2+ARA
F3+ARA
F4+ARA
F5+ARA
3 (n=3)
F5+ARA
F6+ARA
F1+ARA
F2+ARA
F3+ARA
F4+ARA
4 (n=3)
F4
F5
F6
F1
F2
F3
5 (n=3)
F3
F4
F5
F6
F1
F2
6 (n=3)
F2
F3
F4
F5
F6
F1
F1 = Abrocitinib oral suspension formulation 1 under fasted conditions.
F2 = Abrocitinib oral suspension formulation 2 under fasted conditions.
F3 = Abrocitinib oral suspension formulation 3 under fasted conditions.
F4 = Abrocitinib oral suspension formulation 4 under fasted conditions.
F5 = Abrocitinib oral suspension formulation 5 under fasted conditions.
F6 = Abrocitinib oral suspension formulation 6 under fasted conditions.
ARA = Famotidine 40 mg under fasted condition.
Abrocitinib oral suspension formulations 1 to 6 for tasting will be offered to all participants 
in a blinded fashion. Participants randomized to Sequence 1-3 will receive famotidine (40 mg 
with 240 mL of room temperature water) 120 minutes before administering a single 200 mg 
dose of abrocitinib oral suspension formulations 1 to 6 with participants fasting for at least 
10 hours before taking abrocitinib. While participants randomized to Sequence 4-6 will 
receive abrocitinib oral suspension formulations 1 to 6 with participants fasting for at least 
10 hours before taking abrocitinib. Participants will place samples into their mouths, swish 
the sample in the mouth for approximately 10 seconds and then swallow it. Each participant 


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will record the sensory attributes at timed intervals of 0 (immediately after dosing), 5, 10, and 
20 minutes after swallowing using the abrocitinib Taste Assessment Questionnaire. Each 
formulation will be tested daily. Participants will be asked as much as possible not to
verbalize their responses and not discuss taste with other participants until after they have 
filled out the response for that formulation in the questionnaire. Participants will cleanse their 
mouths with room temperature water before tasting a formulation. This water will not be 
swallowed. 
For a participant who completes both Parts A and B of the study, the expected duration of 
participation from screening in Part A to the follow-up telephone contact in Part B of the 
study is approximately 11 weeks. While for a participant who completes only Part A or 
Part B of the study, the expected duration of participation from screening to the follow-up 
telephone contact is approximately 10 weeks. Participants who discontinue the study may be 
replaced at the sponsor’s discretion. The replacement participant will receive the same 
treatment sequences as the participant who discontinued.
Data Monitoring Committee or Other Independent Oversight Committee: No
Statistical Methods
For the rBA portion of Part A, natural log-transformed PK parameters (AUCinf, AUClast, and 
Cmax) will be analyzed using a mixed-effect model with sequence, period and treatment as 
fixed effects and participant within sequence as a random effect. For Part B, the data used in 
the analysis will be transcribed and rescaled to a score from 0 to 100 from the raw 
measurements on the questionnaire. The sensory attributes (overall liking, mouthfeel, 
bitterness, sourness, saltiness, tongue/mouth burn) from the taste questionnaires will be listed 
and descriptively summarized by prototype formulation, and question across participants. 
1.2. Schema
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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.
Table 1.
Schedule of Activities (Part A)
Visit Identifiera
Abbreviations used in this table may be found in 
Appendix 9: Abbreviations
Screeningb
Period 1
Periods 2
Period 3
Early Termination/
DC
Days Relative to Day 1
Day -28 to
Day -2
Day -1
Day 
1
Day 
2
Day 3 Day 1 Day 2 Day 3 Day 1 Day 2
Day 3c
Informed consent
X
CRU confinement
X
→
→
→
→
→
→
→
→
→
X
Inclusion/exclusion criteria
X
X
Medical, drug, tobacco and alcohol history
X
X
Physical examinationd
X
X
X
X
Height and weight assessment
X
Safety laboratorye
X
X
X
Demography (including height and weight)
X
Pregnancy test for WOCBP only
X
X
X
Contraception check for WOCBP only
X
X
X
Serum FSH in post-menopausal femalesf
X
Urine drug testing
X
X
Single 12-Lead ECG
X
Xg
X
Supine BP, pulse rate, and oral temperature
X
Xh
X
Serology: HBcAb, HBsAg, HBsAb, HCVAb, HIV 
testsi
X
QuantiFERON® - TB Gold Testj
X
COVID-19 questionnairek
X
X
COVID-19 testingl
X
X
X
COVID-19 check temperaturem
X
X
X
X
X
X
X
X
X
X
X
Study treatment administrationn
X
X
X
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Table 1.
Schedule of Activities (Part A)
Visit Identifiera
Abbreviations used in this table may be found in 
Appendix 9: Abbreviations
Screeningb
Period 1
Periods 2
Period 3
Early Termination/
DC
Days Relative to Day 1
Day -28 to
Day -2
Day -1
Day 
1
Day 
2
Day 3 Day 1 Day 2 Day 3 Day 1 Day 2
Day 3c
CRU discharge
X
Serious and nonserious AE monitoring
X
X
→
→
→
→
→
→
→
→
→
→
Prior/concomitant treatments
X
X
→
→
→
→
→
→
→
→
→
→
a.
Day relative to the first day of study intervention dosing in all periods.
b.
Screening must take place a maximum of 28 days prior to the administration of the study intervention in Period 1.
c.
Day 3 of Period 3 in Part A of the study overlaps with Day -1 of Period 4 in Part B of the study.
d.
A complete physical examination will be done at screening or may be deferred to Day -1 of Period 1 at the discretion of the investigator. A complete physical examination 
would also be performed at the Early Termination/DC visit (if this occurs). A brief physical examination would be performed at Day 3 of Period 3 and could be performed at 
other times if findings during the previous examination or new/open AE, at the discretion of the investigator.
e.
Safety laboratory assessments must be collected following at least a 4-hour fasting. For details on the tests to be performed, please refer to protocol Appendix 2. The 
hematology, urinalysis, and clinical chemistry tests will be performed at screening, each admission to the CRU, at Day -1 of Period 4 in Part B, at study discharge, and early 
withdrawal. Samples will be collected if the reason for DC is related to an AE. Additional assessments may be performed at the discretion of the investigator.
f.
Females who are amenorrheic ≥12 consecutive months only.
g.
To be collected at predose of abrocitinib.
h.
To be collected at predose and 1-hour postdose (around Tmax) of abrocitinib.
i.
HBsAb tested as reflex test only in participants who are HBsAg negative but are HBcAb positive.
j.
QuantiFERON test to be performed at screening. Prior QuantiFERON test is acceptable when performed within the 12 weeks prior to Day 1 of Period 1.
k.
Check exposure to positive participant, residence or travel in area of high incidence and COVID-19 related signs and symptoms. To be done at each visit.
l.
The testing for COVID-19 pathogen by CRU will be performed at Screening and Day -1 of Period 1. For participants admitted for residence, a subsequent COVID-19 test 
will be performed after 4 days (ie, upon completion of 4 × 24 hours in-house), or if they develop COVID-19 like symptom(s).
m.
To be done at least daily during residence. 
n.
As per assigned randomization and treatment schedule. Study intervention administration should be separated by a period of at least 72 hours (washout). 
 
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Table 2.
Schedule of Activities (Part B)
Visit Identifiera
Abbreviations used in this table may be 
found in Appendix 9: Abbreviations
Period 4
Period 5
Period 6
Period 7
Period 8
Period 9
Early Termination/
DC
Follow-upb
Days Relative to Day 1
Day -1c
Day 1
Day 1
Day 1
Day 1
Day 1
Day 1
Day 2
28-35 Days
Informed consentd
CRU confinement
→ 
→
→
→
→
→
→
X
X
Inclusion/exclusion criteriad
Physical examinatione
X
X
Safety laboratoryf
X
X
X
Pregnancy test for WOCBP only
X
X
Contraception check for WOCBP only
X
X
X
X
Single 12-Lead ECG
Xg
X
X
Supine BP, pulse rate, and oral 
temperature
X
Xh
X
X
COVID-19 testing
Xi
COVID-19 check temperaturej
X
X
X
X
X
X
X
Study treatment administration 
X
X
X
X
X
X
Taste Assessment Questionnairek
X
X
X
X
X
X
 
CRU discharge
X
X
Serious and nonserious AE monitoring
 
→
→
→
→
→
→
→ 
→
X
Prior/concomitant treatments
 
→
→
→
→
→
→
→ 
→
X
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Table 2.
Schedule of Activities (Part B)
Visit Identifiera
Abbreviations used in this table may be 
found in Appendix 9: Abbreviations
Period 4
Period 5
Period 6
Period 7
Period 8
Period 9
Early Termination/
DC
Follow-upb
Days Relative to Day 1
Day -1c
Day 1
Day 1
Day 1
Day 1
Day 1
Day 1
Day 2
28-35 Days
a.
Day relative to the first day of study intervention dosing in all periods.
b.
Contact may occur via telephone contact and must occur 28 to 35 days from administration of the final dose of study intervention, either in Parts A (in case of early 
termination/DC) or in Part B of the study
c.
Day -1 of Period 4 in Part B of the study overlaps with Day 3 of Period 3 in Part A of the study.
d.
For new participants enrolled in Part B only, all Screening and Day -1 visit procedures will be performed as listed in Table 1 SoA (Part A).
e.
A complete physical examination will be done at screening or may be deferred to Day -1 of Period 4 at the discretion of the investigator for new participants admitting for 
Part B only of the study.  A complete physical examination should be performed on Day 2 of Period 9 or at the Early Termination/DC visit (if this occurs). A brief physical 
examination can be performed at other times if findings during the previous examination or new/open AE, at the discretion of the investigator.
f.
Section 8.2.4 Safety laboratory test assessments consist of hematology, urinalysis, and clinical chemistry.  For details on the tests to be performed, please refer to protocol
Appendix 2. The safety tests will be performed at screening, Day-1 of Period 4, each admission to CRU, at study discharge, and early withdrawal. All assessments must be 
collected following at least a 4-hour fasting period. Samples will be collected if the reason for DC is related to an AE. Additional assessments may be performed at the 
discretion of the investigator. 
g.
To be collected at predose of abrocitinib for new participants enrolled in Part B only.
h.
To be collected at predose and 1-hour postdose (around Tmax) of abrocitinib.
i.
For new participants joining this part of the study, and admitted for residence, a subsequent COVID-19 test will be performed after 4 days (ie, upon completion of 4 × 24 
hours in-house), or if they develop COVID-19 like symptom(s).
j.
To be done at least daily during residence. 
k.
Review taste questionnaire and instructions with participants prior to the first taste assessment on Period 4, Day 1. Each participant will record the sensory attributes at timed 
intervals of 0 (immediately after dosing), 5, 10 and 20 minutes after swallowing the suspension, using a Taste Assessment Questionnaire (see Appendix 8). 
 
 
 
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2. INTRODUCTION
Abrocitinib (also referred to as PF-04965842) is an orally bioavailable potent JAK1 inhibitor
with good selectivity over the broader kinome being developed for the treatment of AD.1
2.1. Study Rationale 
The primary purpose of this study in healthy participants is to estimate the rBA of an oral 
suspension of abrocitinib compared to abrocitinib commercial tablet. Additionally, this study 
will also evaluate the effect of an ARA on PK of abrocitinib commercial tablet and evaluate 
the taste and palatability of six different oral suspensions of abrocitinib to help in guiding the 
selection and development of abrocitinib pediatrics formulation.
2.2. Background
2.2.1. Mechanism of Action/Indication
The JAK family, including JAK1, JAK2, JAK3 and TYK2, is a group of cytoplasmic 
tyrosine kinases that mediates signal transduction via interactions with Type 1 and Type 2 
cytokine receptors critical for leukocyte activation, proliferation, survival and function. 
Cytokine receptors demonstrate restricted association with JAKs such that different receptors 
or receptor classes preferentially utilize a given JAK dimer or trimer combination to 
transduce their signal.1 JAK1 pairs with JAK3 to mediate γ-common cytokine signaling and 
also with JAK2 or TYK2 to transmit the signals of additional cytokines important in 
inflammation and immune responses including IL-4, -5, -6, -13, -21, -31, TSLP, IFN-γ, and 
IFN-α. JAK2 homodimers are critical for the signaling of hematopoietic cytokines and 
hormones including erythropoietin, IL-3, granulocyte-macrophage colony-stimulating factor 
and prolactin. IL-12 and IL-23 are dependent on TYK2 and JAK2 for transmitting their 
signals.1
Following cytokine activation, receptor-associated JAKs are phosphorylated, and in turn 
phosphorylate specific sites on the receptor intracellular domain. Phosphorylation of specific 
sites on the intracellular domain of the receptor allows for the recruitment of STATs that can 
subsequently be phosphorylated by JAKs.2 Phosphorylated STAT molecules are released
from the receptor, translocate to the nucleus where they bind to specific sites on the DNA 
and regulate gene transcription.3
Key cytokines implicated in the pathophysiology of AD including IL-4, IL-5, IL-13, IL-22,
IL-31, and IFN-, require JAK1 for signal transduction, suggesting that selective JAK1 
inhibitors, that modulate the activity of these cytokines, represent a compelling approach to 
the treatment of inflammatory skin diseases such as AD.4
Abrocitinib is an orally bioavailable small molecule that selectively inhibits JAK1 by 
blocking the ATP binding site. Abrocitinib has a high degree of selectivity against other 
kinases: 28-fold selectivity over JAK2, >340-fold over JAK3 and 43-fold over TYK2, as 
well as a good selectivity profile over the broader range of human kinases. The selective 
inhibition of JAK1 will lead to modulation of multiple cytokine pathways involved in the 
pathophysiology of AD, including IL-4, IL-13, IL-31 and IFN-. Data from a Phase 2b POC 
study (B7451006) that evaluated participants with moderate to severe AD have shown 


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positive efficacy, as well as an acceptable safety profile, sufficient to support further clinical 
development in a larger Phase 3 program.
2.2.2. Overview of Disease State
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 the quality
of life. Over the past 50 years, AD has become more prevalent, especially in industrialized, 
temperate countries such as the US.5,6 Earlier reports indicated that, in up to 70% of cases, 
the disease greatly improves or resolves until late childhood, however more recent findings 
suggest that disease activity remains manifest for a prolonged period of time. Based on a total 
of 7157 participants enrolled in the PEER study, comprising a total of 22,550 person-years7,
it was concluded that symptoms associated with AD seem to persist well into the second 
decade of a child’s life and likely longer. At every age, more than 80% of PEER study
participants had symptoms of AD and/or were using medication to treat their AD.
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 was approved as a topical treatment in December 2016 by the FDA for use 
in participants with mild to moderate AD. In addition, dupilumab, an injectable monoclonal 
antibody targeting IL-4 and IL-13 was approved for the treatment of AD. Additional 
treatments generally reserved for severe AD include phototherapy (eg, ultraviolet A light 
with or without psoralen, ultraviolet B light narrowband or broadband) and systemic agents 
(eg, corticosteroids, cyclosporine, recombinant IFN-, mycophenolate mofetil, methotrexate, 
azathioprine, IV immunoglobulin).8 Of the currently available therapies, none offers a cure; 
therefore, the main aims of existing treatments are to reduce the occurrence of acute flares, 
to increase the time between relapses, and to reduce pruritus and the resulting sleep 
disturbance.9,10
Other systemic agents to treat AD are under clinical development or have been approved.
Dupilumab, an injectable human monoclonal antibody targeting IL -4 and -13, was approved 
by the FDA in March 2017 and received marketing authorization in Europe in September 
2017, and offers a novel mechanism of action for the treatment of moderate to severe AD. 
However, the approved dosing for dupilumab as an initial dose of 2 × 300 mg subcutaneous 
injections followed by 300 mg every other week injections may limit the desirability of this 
route of treatment.
2.2.3. Rationale for Development of Abrocitinib
Abrocitinib is being developed as an oral treatment for participants with moderate to severe 
AD based on its mechanism of action, and the clinical results obtained in Phase 1 and 
Phase 2 studies. The clinical development program for abrocitinib includes healthy
participants, participants with psoriasis and participants with AD. 
Abrocitinib pediatric program will be initiated to fulfill the regulatory requirements. Critical 
to the regulatory requirements is the development and filing of a pediatric age-appropriate 


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formulation for AD participants aged 6 months to <12 years, with rBA similar to currently 
developed abrocitinib commercial tablet and with acceptable palatability. Thus, this study 
will be conducted to estimate the rBA of an oral suspension formulation of abrocitinib 
compared to abrocitinib commercial tablet. The potential effects of alterations in 
gastrointestinal pH induced by an ARA on the PK of abrocitinib commercial tablet and its 
major metabolite are also evaluated in this study. A taste evaluation will also be conducted to 
assess the taste and palatability of 6 different oral suspension formulations for abrocitinib. 
The results of this taste assessment will help in guiding the selection and development of 
abrocitinib pediatrics formulation and inform whether taste masking is required for the 
commercial pediatric formulation.
2.2.4. Nonclinical Pharmacology
Abrocitinib inhibits cytokines implicated in AD pathogenesis. For example, in vitro,
abrocitinib inhibits IL-4 and IL-13 signaling in B cells, monocytes and keratinocytes, IL-4
signaling in T cells and IL-31 signaling in THP-1 cells. Abrocitinib also inhibits IL-22 in
keratinocytes and IFN-, IFN-, IL-6 and other JAK1 dependent cytokines in PBMCs and
human whole blood. The primary human metabolites of abrocitinib (M1 and M2) showed a
profile of cytokine inhibition, via JAK1-dependent pathways, similar to the parent compound
abrocitinib, while M4 was pharmacologically inactive. In AIA rats, abrocitinib exhibited a
significant and maximal inhibition of disease for this model as well as significant inhibition
of cytokine dependent STAT phosphorylation in ex vivo stimulated whole blood. Significant 
abrocitinib inhibition (>50%) of binding or enzyme activity of MAO-A and KDR kinase 
(VEGFR2) was observed, with IC50 values that were respectively 4.8x and 1.0x the unbound 
human Cmax at a clinical dose of 200 mg QD. 
In vitro safety pharmacology studies were conducted to assess potential hERG (GLP) and
Nav1.5 (non-GLP) inhibition and the IC50 was 76x and 240x, respectively, at the unbound
human Cmax. These ion channel in vitro assessments satisfy ICH S7A/B guidelines. In the
broad ligand profile screen, less than 50% inhibition of calcium channel binding was
observed. Overall, the nonclinical in vitro data for abrocitinib (and M1, M2, and M4) 
contribute to the weight of evidence for no significant effects at clinically relevant 
concentrations on the primary cardiac ion channels (eg, hERG, Nav1.5, or Cav1.2) generally 
considered to be most important for risk assessment of QT prolongation.
In vivo safety pharmacology studies were conducted to assess potential effects on the
nervous, cardiovascular, and pulmonary systems. Abrocitinib produced lower locomotor
activity (horizontal and vertical movements) and body temperature in rats and increases in
heart rate and diastolic blood pressure in cynomolgus monkeys. No other effects on
parameters in the FOB were observed or on the telemetry-based activity measure in the rat or
cynomolgus monkey cardiovascular safety pharmacology studies were observed. No primary
QT signals, including no QTc prolongation, were observed in the cardiovascular safety
pharmacology study in cynomolgus monkeys.


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2.2.5. Nonclinical Pharmacokinetics and Metabolism
Plasma profiling from the [14C]abrocitinib human mass balance study indicated unchanged
abrocitinib as the most prevalent circulating species (26%), with 3 major and more polar
mono-hydroxylated metabolites identified. M1, M2, and M4 are not unique to humans, and
were shown to have sufficient exposures at NOAEL doses in rats (rat/human AUC24 ratios ≥
1) relative to the projected highest therapeutic human dose of 200 mg daily.
In vitro and in vivo metabolite profiling suggested that the primary clearance mechanism for
abrocitinib was CYP-mediated oxidation, with CYP2C19 the primary contributor at 
approximately 50%. CYP metabolism played a minor role (<25%) in the clearance of 
metabolites M1, M2 and M4. Renal excretion of parent drug was limited in the mouse, rat 
and humans, while urinary excretion was the major route of elimination for M1, M2, and M4. 
Abrocitinib, M1, M2, and M4 were not significant competitive inhibitors of CYP enzymes,
but showed varying weak TDI activities versus CYP3A, CYP2C19 and CYP2D6.
Abrocitinib exhibited a weak potential to induce CYP3A4 and CYP2B6, while the M1, M2,
and M4 did not show a greater risk of induction compared to abrocitinib. Clinical results with
midazolam as a victim indicated no significant risk of interaction through inhibition or
induction of CYP3A after abrocitinib administration.
Abrocitinib, M1, M2, and M4 were not significant inhibitors of the major UGT enzymes. 
Abrocitinib did not significantly inhibit SULT enzymes. Clinical results with ethinyl 
estradiol as a victim indicated no significant risk of UGT or SULT inhibition by abrocitinib.
Abrocitinib was not a substrate for OATP1B1 or OATP1B3, nor inhibited these transporters. 
Abrocitinib did not inhibit OAT1, OCT2, or bile salt export pump, but inhibited OAT3, P-gp, 
BCRP, OCT1, MATE1, and MATE2K. Clinical results showed abrocitinib co-administration 
increased dabigatran exposure <2 fold, indicative of the inhibition of dabigatran etexilate 
efflux by P-gp, and showed no significant effect on the exposure of rosuvastatin (BCRP, 
OAT3 probe substrate) or metformin (OCT2, MATE1/2K, OCT1 probe substrate).
Overall risk of a transporter interaction from M1, M2, and M4 is considered low and not
greater than from abrocitinib. M1, M2 and M4 were substrates of OAT3, but not MATE1,
MATE2K, OAT1 or OCT2. Clinical results with probenecid (an OAT3 inhibitor) 
coadministration significantly increased exposure of M1, M2, and M4, but had no effect on
abrocitinib exposure.
2.2.6. Nonclinical Safety
Abrocitinib was assessed in a series of nonclinical toxicity studies. In repeat-dose toxicity 
studies, abrocitinib was administered chronically to rats and cynomolgus monkeys in studies 
up to 6 and 9 months in duration, respectively. In these toxicity studies, abrocitinib-related 
findings were generally consistent with the expected immunomodulatory pharmacology of 
abrocitinib, no unique or unanticipated immunotoxicities were noted after abrocitinib 
administration, and most abrocitinib-related effects had reversed by the end of a 12-week 
recovery phase. 


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Target organs identified included the immune and hematolymphopoietic systems, bone, liver, 
kidney, and skin. In addition, effects on heart rate, diastolic blood pressure, locomotor 
activity, and body temperature were observed in the safety pharmacology studies.
Administration of abrocitinib was also associated with emesis in cynomolgus monkeys and
an increase in small cytoplasmic vacuolation of brown adipose tissue in rats. No evidence of
proliferative or neoplastic lesions was noted in the chronic toxicity studies. 
Abrocitinib is not mutagenic or clastogenic based on the results of a series of in vitro and in
vivo tests for gene mutations and chromosomal aberrations.
Abrocitinib did not affect the male reproductive system, including fertility or
spermatogenesis, but did result in reversible decreased female fertility. Effects on female
fertility (decreased fertility index, corpora lutea, implantation sites) and increased post-
implantation loss were observed in rats at 70 mg/kg/day and 30 mg/kg/day with exposures 
29x and ≥11, respectively, the unbound human AUC at the clinical dose of 200 mg QD and 
were fully reversible following a 1-month recovery. 
Abrocitinib did not cause malformations in rats or rabbits. 
Additionally, data from animal studies revealed that abrocitinib is not genotoxic, and does 
not have an impact on male fertility, and no histopathological changes were noted in the 
testes and epididymides with abrocitinib administration for up to 6 and 9 months at doses up 
to 70 and 75 mg/kg/day in rats and cynomolgus monkeys, respectively, and corresponding 
exposures were 26x and 10x the unbound AUC at the human clinical dose of 200 mg.
Furthermore, in vivo data show that abrocitinib does not have phototoxicity potential.
2.2.7. Clinical Overview
2.2.7.1. Summary of Safety Data from Completed Studies
Based on the clinical experience with abrocitinib and its mechanism of action, the potential 
risks of treatment with JAK inhibitors include: (1) viral reactivation; (2) serious infection and 
opportunistic infections; (3) malignancy and lymphoproliferative disorders; (4) decreased 
lymphocyte counts; (5) decreased neutrophil counts; (6) decreased platelets; (7) alterations in 
the lipid profile; and (8) venous thromboembolism (deep venous thrombosis/pulmonary 
embolism).
In the completed Phase 1 and 2 studies in healthy participants, participants with psoriasis and 
participants with AD, abrocitinib was generally safe and well tolerated.
In the completed Phase 1 studies in healthy participants receiving single doses of abrocitinib
up to 800 mg and multiple doses up to 200 mg BID or 400 mg QD, the most commonly 
reported AEs were diarrhea, nausea, vomiting, headache, acne, and dizziness. Following 
single or multiple dose of abrocitinib, most reported TEAEs were mild or moderate in 
severity. In study B7451001, during the single-ascending dose phase, 1 participant in the 
placebo group had maximum QTcF interval of 450 - <480 msec, and 1 participant in the 
abrocitinib 800 mg treatment group had maximum QTcF interval increase from baseline of 
30 to <60 msec. In the multiple-ascending dose phase, 3 participants (1 each in the placebo, 


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abrocitinib 30 mg QD, and 100 mg QD treatment groups) had maximum QTcF interval of 
450 - <480 msec, and 2 participants in the abrocitinib 200 mg BID treatment group had 
maximum QTcF interval increase from baseline of 30 to <60 msec. 
In the completed Phase 2 study in participants with moderate to severe psoriasis (B7451005), 
the most frequently reported AEs across the abrocitinib treatment groups (200 mg BID, 
200 mg QD, and 400 mg QD) were nausea, followed by headache. Other commonly reported 
AEs include neutropenia and neutrophil counts decreased, thrombocytopenia and platelet 
count decreased. One of the participants in the 200 mg QD group with an AE categorized as 
infections and infestations was reported as having VIIth nerve paralysis (Bell’s palsy) and 
later developed herpes zoster (shingles). The incidence of normal and abnormal ECG 
recordings was similar across all treatment groups at each time point. None of the abnormal 
ECG recordings were determined to be clinically significant by the investigator.
In the completed 12-week Phase 2b study (B7451006) in participants with AD, AEs and 
SAEs were numerically higher in participants receiving abrocitinib (10, 30, 100, and 200 mg 
QD) compared to placebo, but did not appear to increase with dose. The most common AEs 
were in the infections and infestations, skin and subcutaneous tissue disorders and 
gastrointestinal disorders SOC, and the majority of the AEs were mild. The most commonly 
reported TEAEs across all the treatment groups were dermatitis atopic (38 events), and viral 
upper respiratory tract infection (33 events). The most frequently reported treatment related
TEAE was nausea. There were 2 cases of nonserious herpes zoster, one in the 10 mg group 
(not treatment-related), and one in the 30 mg group (treatment-related). There were 
2 participants (doses of ≥100 mg QD) with treatment related SAEs reported, the SAEs were 
eczema herpeticum and pneumonia. One participant randomized to the abrocitinib 10 mg 
group reported an SAE of malignant melanoma. Dose dependent mean platelet count
decreases from baseline were observed with a nadir at Week 4. At Week 4 the mean platelet 
count and the 90% CI were within the normal reference range for both the 100 mg dose and 
200 mg dose. In these treatment groups, the mean platelet count increased towards baseline 
after Week 4. There were no clinically significant findings in vital signs or physical 
examinations. Most of the ECG results were normal. The incidence of normal and abnormal 
ECG recordings was similar between abrocitinib and placebo groups at each time point.
In the completed 12-week Phase 3 study (B7451012) in adult and adolescent participants 
aged 12 years and older with moderate to severe AD, the most frequent all-causality TEAEs 
that occurred in ≥5% of participants of any treatment group (100 mg QD and 200 mg QD) 
were nausea, nasopharyngitis, upper respiratory tract infection, headache, and dermatitis 
atopic. Nausea was the most frequently reported treatment-related TEAE with ≥5% higher 
incidence in the abrocitinib treatment groups compared with the placebo group. Majority of 
TEAEs reported were mild to moderate in severity.
Similarly, safety data from the completed 12-week Phase 3 study (B7451013) in adult and 
adolescent participants aged 12 years and older with moderate to severe AD, have reported 
similar TEAEs to the ones observed in study B7451012. The safety data reported in this 
study showed that the most frequent all-causality TEAEs that occurred in ≥5% of participants 
of any treatment group (100 mg QD and 200 mg QD) were nausea, nasopharyngitis, upper 


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respiratory tract infection, headache, and dermatitis atopic. Nausea was the most frequently
reported treatment-related TEAE with ≥5% higher incidence in the abrocitinib 200 mg 
treatment group compared with the placebo group. Majority of TEAEs reported were mild to 
moderate in severity.
2.2.7.2. Summary of Abrocitinib Pharmacokinetics, Metabolism and In Vitro 
Enzymology
2.2.7.2.1. Single and Multiple Dose Pharmacokinetics
Abrocitinib was absorbed rapidly following single oral solution/suspension doses of 3 mg to 
200 mg with median time to Tmax observed less than 1 hour (ranging from 0.55 to 
0.77 hours), and more slowly at the higher doses with median Tmax of 1.5 and 4.0 hours for 
the 400 mg and 800 mg doses, respectively 
 Following attainment of Cmax, 
the disposition of abrocitinib generally showed a monophasic decline at the lower doses of 3 
to 30 mg (mean apparent t½ of 1.9 to 2.5 hours) while a biphasic decline was observed at 
doses of 100 to 800 mg with a mean t½ of 3.6 to 4.9 hours. Plasma abrocitinib Cmax appeared 
to increase proportionally across the entire dose range from 3 mg to 800 mg, while increases 
in AUCinf were greater than proportional at doses of 400 and 800 mg. For the 2-fold doses 
increase between 200 to 400 mg and between 400 to 800 mg, the mean AUCinf values in 
Western participants in this study appeared to increase approximately 3.5- and 2.7-fold, 
respectively.
On Day 10 of multiple-dose administration, abrocitinib was absorbed rapidly with median 
Tmax of about 1 hour or less (ranging from 0.50-1.05 hours) across the entire range of doses, 
from a total daily dose of 30 mg (30 mg QD) up to 400 mg (200 mg BID or 400 mg QD). 
Following attainment of Cmax, the disposition of abrocitinib was consistent with that observed 
following single-dose administration, showing a biphasic decline following all but the lowest 
dose and a mean t½ of about 2.8 to 5.0 hours. Plasma Cmax and AUCtau both appeared to show 
a trend towards greater than proportional increases at doses higher than 200 mg given 
once-daily. Geometric mean values for the observed Rac, that compares AUCtau for 
multiple-dose administration to AUCtau for single-dose administration, ranged from 
1.3 to 1.5 for QD dosing and 1.3 to 2.3 for BID dosing. Similar ratios for Cmax comparison 
(Rac, Cmax) ranged from 1.1 to 1.3 for QD dosing and from 1.3 to 2.8 for BID dosing. These 
results showed that drug concentration accumulation after repeated oral QD or BID 
administration is less than about 1.5- and 2.3-fold, respectively; at doses up to 200 mg QD, 
the accumulation was minimal and generally consistent with the prediction from t½. 
At a single 800-mg dose, the geometric mean Cmax was similar in Western and Japanese 
participants. However, geometric mean AUCinf was 26% higher in Western participants than 
that observed in Japanese participants. Geometric mean Cmax and AUCtau following 
multiple-dose administration of 200 mg BID was 17% and 56% higher, respectively, in the 
Western participants than in Japanese participants. 
The urinary recovery of abrocitinib was low, with <4% of the dose recovered unchanged in 
urine across all doses and regimens in all cohorts in 
 
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The BA of a solid dose formulation of abrocitinib relative to a suspension formulation was 
evaluated in an open label, single-dose, 3-way crossover study in 12 healthy participants 
under fasting and fed conditions 
 Following single oral 400 mg doses 
under fasted conditions, Cmax was reached rapidly for the oral suspension (median Tmax
0.52 hours) and more slowly for the tablet formulation (4 × 100 mg, median Tmax 2.0 hours). 
When the tablet was administered under fed conditions, Tmax was further delayed with a 
median value of 4.0 hours. Mean t½ was 4.9 hours for the oral suspension fasted, 5.3 hours 
for the tablet fasted, and 3.2 hours for the tablet under fed conditions. Relative BA of 
4 × 100 mg abrocitinib tablets compared to 400 mg oral suspension under fasted condition 
was 96.54% and the 90% CI for the ratio (tablet/suspension) of adjusted geometric mean 
AUCinf values was (90.31%, 103.21%), within the 80% to 125% interval demonstrating 
equivalence of total exposure. The ratio (90% CI) for Cmax was 79.48% (62.88%, 100.46%). 
Administration of 4 × 100 mg abrocitinib tablets with food did not change AUCinf and 
appeared to result in slightly lower Cmax with reduced variability compared to fasted 
conditions. The ratio (90% CI) of adjusted geometric means for fed/fasted administration was 
100.70% (94.42%, 107.40%) for AUCinf and 95.56% (76.22%, 119.82%) for Cmax. The 
magnitude of decrease in Cmax (<5%) was not considered to be clinically important. 
Therefore, abrocitinib can be administered with or without food. There were no clinically 
significant changes in ECG findings during the study.
2.2.7.2.2. Metabolism and In Vitro Enzymology
In vitro and in vivo metabolite profiling in rat, monkey, and human indicated that the primary 
clearance mechanism for abrocitinib was CYP-mediated oxidative metabolism. No unique 
human metabolites were observed clinically compared to metabolite profiling in rat and 
monkey. There was no evidence of chiral inversion in human plasma samples. Plasma 
profiling from the [14C]abrocitinib human mass balance study indicated parent as the most 
prevalent circulating species (26%), with 3 major and more polar mono-hydroxylated 
metabolites identified: 340-1 (3-hydroxypropyl, 11%), 340-2a (2-hydroxypropyl, 12%), and 
340-4 (pyrrolidinone pyrimidine, 14%).
In vitro human CYP450 phenotyping studies indicated that CYP2C19 (fraction metabolized 
[fm] ~0.5), CYP2C9 (fm ~0.3), CYP3A4 (fm ~0.1), and CYP2B6 (~0.1) were involved in 
the metabolism of abrocitinib. Early assessment of clinical genotypes from FIH participants
indicated PK variability of all available non-wild-type genotypes (CYP2C19*1/*2, *2/*3, 
*2/*2, *1/*17, and *17/*17; CYP2C9*1/*2, *1/*3) were within the variability seen in 
wild-type CYP2C9*1/*1 and CYP2C19*1/*1 participants. 
Abrocitinib did not inhibit the major CYP enzymes (IC50 values >100 μM) by competitive 
inhibition and did not cause time-dependent inhibition without the reduced form of NADPH. 
In the presence of NADPH, abrocitinib caused relatively weak time-dependent inhibition of 
CYP2C19 (IC50, 42 μM), CYP2D6 (IC50, 92 μM), and CYP3A4/5 (IC50, 40 to 81 μM).
Abrocitinib concentration dependently induced CYP3A4 mRNA in 2/3 hepatocyte lots at 
≥10 μM and CYP2B6 mRNA in 3/3 hepatocyte lots at ≥10 μM. Enzyme activity of CYP2B6 
increased >2-fold at ≥30 μM in 1 of 3 lots of hepatocytes. Conversely, abrocitinib caused a 
concentration-dependent decrease in CYP3A4 and CYP1A2 enzyme activities in 
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3/3 hepatocyte lots. Clinically, abrocitinib PK showed apparent dose proportionality of single 
and multiple daily doses up to 200 mg, with no significant changes (~ <20%) in the CYP3A 
plasma biomarker 4β-hydroxycholesterol/cholesterol ratio following 10 days of dosing 
Preliminary SimCYP® modelling of abrocitinib dosed 200 mg QD for 
10 days indicated a low risk of precipitating a significant drug interaction with midazolam 
(CYP3A), buproprion (CYP2B6), or mephenytoin (CYP2C19). 
Abrocitinib did not inhibit the major UGT enzymes; all IC50 values >100 μM. Abrocitinib
was not a substrate for OATP 1B1 or OATP1B3, nor inhibited these transporters (IC50 values 
>300 μM). Abrocitinib did not inhibit OAT 1 (IC50 >300 μM) or OCT 2 (IC50 >300 μM), but 
weekly inhibited OAT3 (IC50 = 26 μM), MDR1 (IC50 = 100 μM), OCT1 (IC50 = 44 μM), and 
showed some inhibitory activity of BCRP (IC50 = 9.8 μM), MATE1 (IC50 = 5.5 μM), and 
MATE2K (IC50 = 10.7 μM). Clinically, abrocitinib did not significantly affect 24 hour
urinary creatinine (OCT2 and MATE1/2K substrate) up to doses of 800 mg 
(Study B7451001). Preliminary SimCYP® modelling of abrocitinib dosed at 200 mg QD 
indicated a low risk of precipitating a significant drug interaction with metformin 
(OCT2/MATE substrate) or digoxin (MDR1 substrate).
 
 
 
2.3. Benefit/Risk Assessment
Abrocitinib is not expected to provide any clinical benefit to healthy participants. This study 
is designed primarily to generate safety, tolerability, and PK data for further clinical 
development.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of abrocitinib may be found in the IB, which is the SRSD for this study. The 
SRSD for the ARA, famotidine, is the US package insert.
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3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 
Part A:
•
Estimate the rBA of abrocitinib 200 mg oral 
suspension formulation 1 compared to the 
1×200 mg of abrocitinib commercial tablet 
under fasting condition.
•
Evaluate the effect of a single dose of an ARA
(famotidine 40 mg) on the BA of abrocitinib 
1×200 mg commercial tablet under fasting 
conditions.
•
Plasma abrocitinib PK parameters: AUCinf (if 
data permit), AUClast and Cmax after 
administration of abrocitinib oral suspension 
formulation and commercial tablet.
•
Plasma abrocitinib PK parameters: AUCinf (if
data permit), AUClast and Cmax after 
administration of ARA plus abrocitinib 
commercial tablet.
Part B:
•
Evaluate the taste and palatability of 
6 abrocitinib suspension formulations using a 
200 mg dose.
•
Taste Assessment Survey Scoring Metrics after 
suspension formulation: mouthfeel, bitterness, 
tongue/mouth burn, saltiness, sourness, and 
overall liking.
Secondary: 
Secondary: 
 
 
•
Determine the PK of metabolites (M1, M2 and 
M4) following the administration of 1×200 mg 
of abrocitinib commercial tablet with or without 
an ARA (famotidine 40 mg) in Part A.
•
Evaluate the safety and tolerability following 
oral administration of each of the abrocitinib 
formulations in Parts A and B.
•
PK parameters: AUCinf (if data permit), AUClast
and Cmax after administration of 1×200 mg of 
abrocitinib commercial tablet with or without an 
ARA.
•
Assessment of TEAEs, clinical laboratory tests, 
vital signs, and 12-lead ECGs.
 
 
 
 
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1 randomized, crossover study in healthy participants to estimate the rBA of 
abrocitinib oral suspension (Test formulation) compared to commercial abrocitinib tablet
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(Reference formulation) under fasted condition. The effect of ARA on the BA of abocitinib 
and its metabolites will be evaluated by administering abrocitinib 200 mg commercial tablet 
with or without famotidine 40 mg as an ARA. Part B is to assess the taste and palatability of 
6 different abrocitinib oral suspension formulations, to guide the selection and development 
of abrocitinib pediatrics oral suspension formulation. 
This study consists of 2 parts, as listed below.
Part A: This part of the study will be an open label, randomized, single dose, crossover, 
3-treatment, 6-sequence, 3-periods design. Approximately 18 healthy male and/or female 
participants (18-55 years) will be enrolled and randomized to 1 of 6 possible treatment 
sequences. Participants who discontinue from the study may be replaced at the sponsor’s 
discretion. The replacement participant will receive the same treatment sequences as the 
participant who discontinued. Each randomized treatment sequence will consist of 
3 treatment periods as shown in Table 4.
Table 4.
Randomized Treatment Sequences of Part A
Sequence
Period 1
Period 2
Period 3
1 (n=3)
A
B
C
2 (n=3)
B
C
A
3 (n=3)
C
A
B
4 (n=3)
A
C
B
5 (n=3)
B
A
C
6 (n=3)
C
B
A
Treatment A = Abrocitinib 200 mg commercial tablet only, under fasted conditions.
Treatment B = Abrocitinib 200 mg oral suspension formulation 1, under fasted conditions.
Treatment C = Famotidine 40 mg tablet administered 2 hours prior to abrocitinib 200 mg commercial tablet 
under fasted conditions.
Healthy participants will be screened within 28 days prior to the first administration of the 
study intervention to confirm that they meet the participant selection criteria for the study. 
Eligible participants will be admitted to the CRU on Day -1 and will be confined in the CRU 
until Discharge, which is Day 2 of Period 9, in Part B of the study (SoA), after completing 
both Parts A and B of the study. Day -1 is defined as the day prior to the first day of dosing 
(Day 1). 
In Period 1 through Period 3 of Part A, participants will receive a single 200 mg dose of 
abrocitinib commercial tablet (Treatment A), a single 200 mg dose of abrocitinib oral 
suspension (Treatment B), or 40 mg famotidine tablet administered 120 minutes prior to a 
single dose of 200 mg dose of abrocitinib commercial tablet (Treatment C) after a fast of at 
least 10 hours before taking the study intervention, abrocitinib. All participants will be 
fasting for at least 10 hours before taking abrocitinib.
 
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Part B: 
Participants who complete Part A of the study are expected to proceed to Part B. Part B will 
be a single-blind, randomized, 6-period, cross-over study in healthy male and/or female adult 
participants (18-55 years). A total of 18 healthy participants will be enrolled and randomized 
to 1 of 6 possible treatment sequences. Participants who discontinue from the study may be 
replaced at the sponsor’s discretion. The replacement participant will receive the same 
treatment sequences as the participant who discontinued. Each randomized treatment 
sequence will consist of 6 treatment periods (Table 5).
Table 5.
Randomized Treatment Sequences of Part B
Sequence
Period 4
Period 5
Period 6
Period 7
Period 8
Period 9
1 (n=3)
F1+ARA
F2+ARA
F3+ARA
F4+ARA
F5+ARA
F6+ARA
2 (n=3)
F6+ARA
F1+ARA
F2+ARA
F3+ARA
F4+ARA
F5+ARA
3 (n=3)
F5+ARA
F6+ARA
F1+ARA
F2+ARA
F3+ARA
F4+ARA
4 (n=3)
F4
F5
F6
F1
F2
F3
5 (n=3)
F3
F4
F5
F6
F1
F2
6 (n=3)
F2
F3
F4
F5
F6
F1
F1 = Abrocitinib oral suspension formulation 1 under fasted conditions.
F2 = Abrocitinib oral suspension formulation 2 under fasted conditions.
F3 = Abrocitinib oral suspension formulation 3 under fasted conditions.
F4 = Abrocitinib oral suspension formulation 4 under fasted conditions.
F5 = Abrocitinib oral suspension formulation 5 under fasted conditions.
F6 = Abrocitinib oral suspension formulation 6 under fasted conditions.
ARA = Famotidine 40 mg under fasted condition.
For any new healthy participants joining Part B only to support the achievement of the total 
number of 18 healthy participants enrolled or randomized in this part of the study, screening 
for healthy participants will be performed within 28 days prior to the first administration of 
the study intervention to confirm that they meet the participant selection criteria for the 
study. 
Abrocitinib oral suspension formulations 1 to 6 for tasting will be offered to all participants 
in a blinded fashion. Participants randomized to Sequence 1-3 will receive famotidine (40 mg 
with 240 mL of room temperature water) 120 minutes before administering a single 200 mg 
dose of abrocitinib oral suspension formulations 1 to 6 with participants fasting for at least 
10 hours before taking abrocitinib. While participants randomized to Sequence 4-6 will 
receive abrocitinib oral suspension formulations 1 to 6 with participants fasting for at least 
10 hours before taking abrocitinib. 
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For participants receiving the ARA, famotidine, a 40 mg dose of famotidine tablet will be 
administered 2 hours before administering the study intervention with participants fasting for 
at least 10 hours before taking abrocitinib.
New participants enrolled in Part B only will be admitted to the CRU on Day -1 and will be 
confined in the CRU until Discharge, which is Day 2 of Period 9. On Day 1 of each treatment 
period under fasted conditions, participants will receive famotidine tablet (40 mg with 
240 mL of room temperature water) administered 120 minutes before  a single 200 mg dose 
of abrocitinib oral suspensions (Formulations 1 to 6) or administered a single 200 mg dose of 
abrocitinib oral suspension alone (Formulations 1 to 6), after a fast of at least 10 hours before 
abrocitinib administration. 
For a participant who completes both Part A and Part B of the study, the expected duration of 
participation from screening in Part A to the follow-up telephone contact in Part B of the 
study is approximately 11 weeks. While for a participant who completes only Part A or 
Part B of the study, the expected duration of participation from screening to the follow-up 
telephone contact is approximately 10 weeks. Participants who discontinue from the study 
may be replaced at the sponsor’s discretion. The replacement participant will receive the 
same treatment sequences as the participant who discontinued.
4.2. Scientific Rationale for Study Design
Part A: A crossover design was used in the rBA part of the study following the FDA 
guidance which states that a crossover study design is recommended for BA of IR dosage 
forms. This crossover design reduces variability caused by patient-specific factors, thereby 
increasing the ability to discern differences because of formulation.11
Washout period: The mean elimination half-life of abrocitinib is approximately 3-5 hours; 
thus, a 25 hours washout period is considered adequate for the washout of the abrocitinib
from plasma. During PK sampling, it is the best practice to wait until plasma concentrations 
are BLQ before administration of the next dose to minimize the carryover from the previous 
treatment. Based on previous clinical experience with abrocitinib, a 72-hour washout period 
is sufficient for plasma abrocitinib concentrations to return to BLQ after administration of a 
single dose. Therefore, in this study, a 72-hour washout period has been selected between 
each treatment period in Part A of the study.
Part A of the study will evaluate the effect of an ARA on abrocitinib BA. This assessment 
has been conducted following the FDA guidance recommending that sponsors need to assess 
the susceptibility of a weak base drug, like abrocitinib, to DDI mediated by gastric-pH 
changes (referred to as pH-dependent DDIs). FDA guidance states that concomitant 
administration of an ARA with a weak base drug could alter the BA of the drug. According 
to the FDA guidance, when evaluating the effect of DDI mediated by gastric pH, it is 
preferable to select an ARA that does not exhibit other interacting mechanisms. The effect of 
PPI on CYP2C19 makes it a nonpreferable ARA selection to use in this study as it may 
interfere with abrocitinib metabolism via CYP2C19. Administration of H2 blockers (eg, 
famotidine) ahead (eg, 2 hours) of the investigational drug can maximize the pH-elevating 
effect with a duration of action lasting ~10-12 hours.12,13 Famotidine is a competitive 


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inhibitor of H2 receptors which inhibits both basal and nocturnal gastric secretion. After oral 
administration of famotidine, the onset of the antisecretory effect occurred within 1 hour; the 
maximum effect was dose-dependent, occurring within 1 to 3 hours.14 Intragastric pH after a 
single dose of famotidine 40 mg was shown to rapidly increase to pH >4.0 within 2 hours of 
administration,15 with a duration of inhibition of secretion lasting for 10 to 12 hours. In the 
present study, the maximum allowed dose of famotidine, famotidine 40 mg, will be
administered 2 hours before abrocitinib to achieve its maximal acid-reducing and 
pH-increasing effects. This dose was selected to align with the FDA guidance stating that 
sponsors should select the maximum recommended dose of an ARA to characterize the 
worst-case scenario possible.16
Part B: In Part B, treatments will be presented to the participants in a blinded fashion to 
minimize the potential bias for taste evaluation.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 1.
Abrocitinib pH Solubility Curve
 
 
 
 
 
 
4.2.1. Choice of Contraception/Barrier Requirements 
Human reproductive safety data are not available for abrocitinib, but there is no suspicion of 
human teratogenicity based on the intended pharmacology of the compound. Therefore, the 
use of a highly effective method of contraception is required (see Appendix 4).
 
4.3. Justification for Dose
Single oral doses of 200 mg abrocitinib will be used in this study as it is the highest dose 
evaluated in the Phase 3 AD program. Part A of the study will be performed using the highest 
200-mg tablet strength intended for commercialization in both adults and adolescents. 
Similarly, Part B of the study will include suspension formulations of 200-mg strength, 
similar to the strength used for abrocitinib commercial tablet.
Following administration of a single oral dose of abrocitinib to healthy participants 
 systemic exposure to abrocitinib increased with dose in an approximately 
dose proportional manner up to 200 mg, suggesting linear PK over this dose range. Oral 
0
1
2
3
4
5
6
7
8
9
10
11
12
13
0
2
4
6
8
10
12
14
Solubility (mg/mL)
pH
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doses of abrocitinib as high as 800 mg (single dose), 400 mg QD and 200 mg BID (up to 
10 days) have been found to be safe and well-tolerated. Administration of 400 mg abrocitinib
with food did not increase the exposure. Based on the safety data of abrocitinib and prior 
clinical experience described above, the 200 mg single dose is expected to pose little risk to 
healthy adult participants.
In the present study, the maximum allowed dose of famotidine, famotidine 40 mg, will be 
administered 2 hours before abrocitinib to achieve its maximal acid-reducing and pH-
increasing effects. Intragastric pH after a single dose of famotidine 40 mg was shown to 
rapidly increase to pH >4.0 within 2 hours of administration.15 This dose was selected to 
align with the FDA guidance stating that sponsors should select the maximum recommended 
dose of an ARA to characterize the worst-case scenario possible.16
4.4. End of Study Definition
The end of the study is defined as the date of last scheduled procedure shown in the SoA for 
the last participant in the study.
A participant is considered to have completed the study if he/she has completed all periods of 
the study, including the last Follow-up phone call.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male and/or female participants must be 18 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.
a.
Male participants:
No contraceptive measures are required.


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b. Female participants:
A female participant is eligible to participate if she is not pregnant or 
breastfeeding, and at least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3);
OR

Is a WOCBP and using a contraceptive method that is highly effective 
(with a failure rate of <1% per year), as described in the Contraceptive and 
Barrier guidance (Appendix 4), during the intervention period and for at 
least 28 days after the last dose of study intervention, which corresponds 
to the time needed to eliminate any reproductive safety risk of the study 
intervention(s). The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.

A WOCBP must have a negative highly sensitive (sensitivity of at least 
25 mIU/mL) pregnancy test result at screening. Following a negative 
pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required 
prior the participants receiving the first dose of study intervention and at 
every subsequent study timepoints as per the SoA tables, to confirm the 
participant has not become pregnant.

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.
Type of Participant and Disease Characteristics:
2. Male and/or female participants who are overtly healthy as determined by medical 
evaluation including a detailed medical history, complete physical examination, 
laboratory tests, and cardiovascular tests.
3. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight:
4. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). 
Informed Consent:
5. Capable of giving signed informed consent as described in Section 10.1.2, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
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5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. Participants with moderate to severe GERD symptoms (ie, heartburn and/or 
regurgitation) during the last 6 months.
4. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, 
HBcAb or HCVAb. 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. Evidence or history of clinically significant dermatological condition (eg, AD or 
psoriasis) or visible rash present during physical examination.
7. History of TB (active or latent) or inadequately treated TB infection. Positive 
QuantiFERON® – TB Gold test. 
8. Any history of chronic infections, any history of recurrent infections, any history of 
latent infections, or any acute infection within 2 weeks of baseline (Day -1). 
9. History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent 
localized dermatomal herpes zoster. 
10. Have any malignancies or have a history of malignancies with the exception of 
adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the 
skin, or cervical carcinoma in situ. 
11. History of hypersensitivity, intolerance, or allergic reaction associated to prior 
exposure to famotidine or other H2-receptor antagonists excipients.
Prior/Concomitant Therapy:
12. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. (Refer to Section 6.8 for additional details).


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13. Participants who are vaccinated with vaccines that have live components (or live 
attenuated vaccines) within the 6 weeks prior to the first dose of abrocitinib or who 
are expected to be vaccinated during treatment or during the 6 weeks following 
discontinuation of abrocitinib.
NOTE regarding COVID vaccines with authorization or approval for 
emergency use:
There is no requirement for washout of COVID vaccines prior to the first dose of 
abrocitinib if the vaccine is not live attenuated (eg, mRNA, utilizing a viral vector, 
inactivated virus). 
There is no protocol-specified requirement for the interruption of abrocitinib dosing 
prior to or after vaccination if the COVID vaccine is not live attenuated.
Prior/Concurrent Clinical Study Experience:
14. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of study intervention
used in this study (whichever is longer). 
Diagnostic Assessments:
15. A positive urine drug test.
16. 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.
17. Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that 
may affect participant safety or interpretation of study results (eg, baseline QTcF
interval >450 msec, complete left bundle branch block, signs of an acute or 
indeterminate-age- myocardial infarction, ST-T interval changes suggestive of 
myocardial ischemia,  second and 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 interpreted by a physician experienced in 
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18. 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/SGOT or ALT/SGPT level 1.5 × ULN.

TBili level >1.0 × 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 1.0 × ULN.

eGFR 80 mL/min/1.73 m2 (see Appendix 2 for CKD-EPI formula).
19. Participants with abnormal complete blood count test results (eg, hemoglobin, 
platelets, WBCs- including lymphocytes, neutrophils) as assessed by the 
study-specific laboratory, and confirmed by a single repeat test, if deemed necessary.
Other Exclusions:
20. 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).
21. Pregnant female participants; breastfeeding female participants; female participants of 
childbearing potential who are unwilling or unable to use 1 highly effective method 
of contraception as outlined in this protocol (see Appendix 4, Section 10.4.4) for the 
duration of the study and for at least 28 days after the last dose of study intervention.
22. Use of tobacco- or nicotine- containing products in excess of the equivalent of 
5 cigarettes per day.
23. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to first dose of study intervention.
24. Unwilling or unable to comply with the criteria in Lifestyle Considerations, 
Section 5.3 of this protocol.
25. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members. 


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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 and 10 hours prior to the collection of the predose 
PK sample.

Water is permitted until 1 hour prior to study intervention administration. Water may 
be consumed without restriction beginning 1 hour after abrocitinib dosing on Day 1 
of each treatment period. Noncaffeinated drinks (except grapefruit or 
grapefruit-related citrus fruit juices—see below) may be consumed with meals and 
the evening snack.

Lunch will be provided approximately 4-5 hours after abrocitinib dosing.

Dinner will be provided approximately 9 to 10 hours after abrocitinib dosing.

An evening snack may be permitted.

Participants will refrain from consuming red wine, grapefruit, or grapefruit-related 
citrus fruits (eg, Seville oranges, pomelos, fruit juices) from 7 days prior to the first 
dose of abrocitinib and during confinement in the CRU.

While participants are confined, their total daily nutritional composition should be 
approximately 55% carbohydrate, 30% fat, and 15% protein. The daily caloric intake 
per participant should not exceed approximately 3200 kcal.
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 (or as specified above for red 
wine) to admission to the CRU and continue abstaining from alcohol throughout their 
stay at the CRU. Participants may undergo an alcohol breath test or blood alcohol test 
at the discretion of the investigator.

Participants will abstain from the use of tobacco- or nicotine-containing products for 
24 hours prior to dosing and during confinement in the CRU. 
5.3.3. Activity

Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests. Walking at a normal pace will be permitted.


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
In order to standardize the conditions on PK sampling days, participants will be 
required to refrain from lying down (except when required for BP, pulse rate, and 
ECG measurements), eating, and drinking beverages other than water during the first 
4 hours after abrocitinib dosing.
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 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)
considering that their risk for pregnancy may have changed since the last visit. In addition, 
the investigator or designee will instruct the participant to call immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the participant
or partner.
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 on the DCT.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened if they fail the screening evaluation for reasons related to incidental transitory 
conditions. If a participant cannot return for the Baseline visit (the day of first dose 
administration) within the protocol specified screening period of 28 days (ie, Screening visit 
to Day 1 of Period 1 in Part A; or Screening visit to Day 1 of Period 4 for any new 
participants enrolled in Part B of the study only), the participant will be considered a screen 
failure. If a participant is rescreened, a second informed consent must be obtained and 
documented, and all screening tests and procedures must be repeated. All results must be 
obtained before the participant may receive the first dose of study intervention.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to study intervention.
6.1. Study Intervention(s) Administered
For this study, commercial tablet formulation of abrocitinib 200 mg tablet, 6 oral suspension 
formulations of abrocitinib and famotidine 40 mg tablets will be administered. Commercial 


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tablet of abrocitinib 200 mg for oral administration will be supplied to the CRU as packaged 
bulk bottles and labeled according to local regulatory requirements. The packaged bulk 
bottles will be provided to the site for dispensing by the pharmacy. 
Abrocitinib 25 mg/mL oral suspension will be supplied as a white to off-white ready to use 
suspension, packaged in a 75 mL HDPE white, round bottle with a heat induction seal and 
white child resistant cap. Each bottle of abrocitinib will contain 60 mL of oral suspension. As 
part of a rBA in Part A and taste assessment study in Part B, 25 mg/mL suspensions of 
abrocitinib will be dosed to participants. Six suspension formulations will be evaluated in the 
study, the first suspension formulation (Formulation 1) will be used for PK assessment, in 
Part A of the study, and taste evaluation, in Part B of the study. While, the 5 others 
(Formulation 2-6) will be used only in Part B of the study for taste evaluation only as 
outlined in Table 6. 
Famotidine 40 mg tablets will be supplied by the CRU.


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Table 6.
Summary of Abrocitinib Oral Suspension Formulations to be administered for PK and Taste Assessment
Formulation
 
Supply
Use
1
Provided by Pfizer
Pharmaceutical Sciences
DMID D1900119
Abrocitinib 25 mg/mL Oral Suspension in 75 mL HDPE bottle 
(60 mL)
PK + Taste Evaluation
2
Provided by Pfizer
Pharmaceutical Sciences
Provided by Pfizer Pharmaceutical Sciences
DMID D1900120
Abrocitinib 25 mg/mL Oral Suspension in 75 mL HDPE bottle 
(60 mL, without flavour)
Taste Evaluation only
3
Prepared at CRU
4
Prepared at CRU
5
Prepared at CRU
6
Prepared at CRU
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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6.1.1. Administration
Part A: Following an overnight fast of at least 10 hours, participants will receive the study 
intervention, abrocitinib, at approximately 0800 hours (plus or minus 2 hours). Investigator 
site personnel will administer the study intervention during each period with ambient 
temperature water to a total volume of approximately 240 mL. Participants will swallow the 
study intervention whole and will not manipulate or chew the study intervention prior to 
swallowing. For participants receiving the ARA, famotidine, a 40 mg dose of famotidine 
tablet will be administered 2 hours before administering the study intervention, abrocitinib, 
with participants fasting for at least 10 hours before taking abrocitinib.
Part B: Abrocitinib oral suspension formulations 1 to 6 for tasting will be offered to all 
participants in a blinded fashion. Following an overnight fast of at least 10 hours, participants 
will receive the study intervention, abrocitinib, at approximately 0800 hours (plus or minus 
2 hours). Participants will place samples into their mouths, swish the sample in the mouth for 
approximately 10 seconds and then swallow it. Each participant will record the sensory 
attributes at timed intervals of 0 (immediately after dosing), 5, 10 and 20 minutes after 
swallowing using the Abrocitinib Taste Assessment Questionnaire. Each formulation will be 
tested daily. Participants will be asked as much as possible to not verbalize their responses 
and not discuss taste with other participants until after they have filled out the response for 
that formulation in the questionnaire. Participants will cleanse their mouth with room 
temperature water before tasting a formulation. This water will not be swallowed. For 
participants receiving the ARA, famotidine, a 40 mg dose of famotidine tablet will be 
administered 2 hours before administering the study intervention with participants fasting for 
at least 10 hours before taking abrocitinib.
For both Part A and Part B of the study, participants will be instructed to fast for at least 
10 hours before receiving abrocitinib. Water will be withheld for 1-hour predose and 1 hour 
after study treatment administration, and food will only be allowed after 4 hours postdose.
In order to standardize the conditions throughout the study, all participants will be required to 
refrain from lying down (except when required for BP, pulse rate, and ECG measurements), 
eating, and drinking beverages other than water during the first 4 hours after dosing.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 


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


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assistant/technician, or pharmacist). The tablets will be provided in unit dose containers and 
labeled in accordance with Pfizer regulations and the clinical site’s labeling requirements.
For the oral suspension formulations of abrocitinib, see the DAI for instructions on how to 
prepare the study intervention for administration. Study intervention should be prepared and 
dispensed by an appropriately qualified and experienced member of the study staff (eg, 
physician, nurse, physician’s assistant, nurse practitioner, pharmacy assistant/technician, or 
pharmacist) as allowed by local, state, and institutional guidance. A second staff member will 
verify the dispensing.
The handling of famotidine tablets should be according to the product package insert.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
The investigator, or delegated staff, will assign participant numbers to the participants as they 
are screened for the study. Pfizer will provide a randomization schedule to the investigator 
and, in accordance with the randomization numbers, the participant will receive the study 
treatment regimen assigned to the corresponding randomization number.
6.4. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the DCT. 
Study site personnel will examine each participant’s mouth to ensure that the study 
intervention was ingested.
6.5. Dose Modification
Dose modification is not allowed in this study. 
6.6. Continued Access to Study Intervention After the End of the Study
No intervention will be provided to study participants at the end of their study participation.
6.7. Treatment of Overdose
For this study, any dose of abrocitinib greater than 800 mg within a 24-hour time period 
(±12 hours) will be considered an overdose.
The sponsor does not recommend specific treatment for an overdose for abrocitinib. 
Observation and if required, supportive care would be expected.


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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 abrocitinib (whichever is 
longer).
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the DCT.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis within 3 days from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case
basis).
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.  
6.8. Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. 
Vaccines with live components (or live attenuated vaccines) are prohibited within the 
6 weeks prior to the first dose of abrocitinib, during the study treatment and during the 6 
weeks following the discontinuation of abrocitinib.
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.


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6.8.1. Rescue Medicine
There is no rescue therapy to reverse the AEs observed with abrocitinib; standard medical 
supportive care must be provided to manage the AEs. 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: 

AE requiring discontinuation in investigator’s view;

Pregnancy;

Positive COVID-19 test.
If study intervention is permanently discontinued, the participant will not remain in the study 
for further evaluation. See the SoA for data to be collected at the time of discontinuation of 
study intervention.
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 study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;

Behavioral, compliance or administrative reasons.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. If the participant withdraws from the 
study and also withdraws consent (see Section 7.2.1) for disclosure of future information, no 
further evaluations should be performed and no additional data should be collected. The 
sponsor may retain and continue to use any data collected before such withdrawal of consent.


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When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the DCT and reported on the CT SAE Report.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate DCT 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. Counsel the participant on the importance of maintaining the 
assigned visit schedule, and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
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.


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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 
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 group may be 
used in a subsequent group without rescreening, provided laboratory results obtained prior to 
the first dose administration meet eligibility criteria for this study. In addition, other clinical 
assessments or specimen collections, eg, retained research samples, may be used without 
repeat collection, as appropriate. 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
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 
wellbeing 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.
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 
230 mL per participant. 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.


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To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy of the protocol.
8.1. Efficacy Assessments
Not Applicable.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant-reported symptoms. 
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation. 
Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 
surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Section 8.3.1 to Section 8.3.3.
8.2.2. Vital Signs
Supine BP and pulse rate will be measured at times specified in the SoA of this protocol. 
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.
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. 


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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.
8.2.2.1. Temperature
Temperature will be measured orally. No eating, drinking, or smoking is allowed for 
15 minutes prior to the measurement.  Temperature will be done at least daily during 
residence.
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 of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS 
complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) 
should not be used given the potential risk of discrepancies with ECGs acquired using 
standard limb lead placement. All scheduled ECGs should be performed after the participant
has rested quietly for at least 5 minutes in a supine position. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons 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 QT 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 QTc values from these repeated ECGs remain above 
the threshold value, then a single ECG must be repeated at least hourly until QTc values from 
2 successive ECGs fall below the threshold value that triggered the repeat measurement.
If a) a postdose QTcF interval remains ≥60 msec from the baseline and is >450 msec; or b) 
an absolute QT 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 criteria listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.


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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 DCT. 
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 28 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
Participants may undergo random urine drug testing at the discretion of the investigator. 
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.2.5. COVID-19 Specific Assessments
Participants will be tested for SARS-COVID-19 infection by PCR prior to being admitted to 
the clinic for confinement and a subsequent COVID-19 test will be performed after 4 days 
(ie, upon completion of 4 × 24 hours in-house), or if they develop COVID-19 like symptoms. 
Additional testing may be required by local regulations or by the PI.
8.2.6. Pregnancy Testing
Pregnancy tests will 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 
(admission during Period 1), prior to 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 
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8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the Investigator or 
other healthcare providers (clinical signs, test results, etc.).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or that caused the participant to discontinue the 
study intervention (see Section 7.1).
During the active collection period as described in Section 8.3.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days after the last administration of the study intervention.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the DCT and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and he/she 


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considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the DCT
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 DCT.
The investigator is to record on the DCT all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant. Reporting of AEs and SAEs for participants who 
fail screening are subject to the DCT requirements as described in Section 5.4.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-Up of AEs and SAEs
After the initial AE/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.


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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 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the investigation product. Such 
exposure may or may not lead to the occurrence of an AE or SAE. Persons at risk for 
environmental exposure include healthcare providers, family members, and others who may 
be exposed. An environmental exposure may include exposure during pregnancy, exposure 
during breastfeeding, and occupational exposure.
Any such exposure to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness. 
8.3.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception. 

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental EDP:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion.


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
A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion then exposes his female partner prior to or around the 
time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 28 days after 
the last dose.  

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a DCT; 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 
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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 EDB occurs if:

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental EDB
is a female family member or healthcare provider who reports that she is 
breastfeeding after having been exposed to the study intervention by ingestion.
The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the CT SAE Report Form. When 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 DCT. However, a copy of the completed 
CT SAE Report Form is maintained in the investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the CT SAE Report Form regardless of 
whether there is an associated SAE. Since the information about the occupational exposure 
does not pertain to a participant enrolled in the study, the information is not recorded on a 
DCT; however, a copy of the completed CT SAE Report Form must be maintained in the 
investigator site file.
8.3.6. Cardiovascular and Death Events
Not Applicable.


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8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not Applicable.
8.3.8. Adverse Events of Special Interest
Not applicable.
8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies
Not Applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the DCT
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.
Other examples include, but are not limited to:

The administration of expired study intervention;

The administration of an incorrect study intervention;

The administration of an incorrect dosage;


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•
The administration of study intervention that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the DCT, 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 DCT and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
DCT.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Pharmacokinetics 
8.4.1. Plasma for Analysis of Abrocitinib and Metabolites
Blood samples of approximately 6 mL, to provide approximately 3 mL of plasma will be 
collected into appropriately labeled tubes containing K2EDTA for measurement of plasma 
concentrations of abrocitinib and its metabolites PF-06471658/M1, PF-07055087/M2, and 
PF-07054874/M4 as specified in the 
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 (eg, within 6 minutes of a 60-minute sample) 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 data collection tool (eg, DCT). 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 data collection tool (eg, DCT). 
Plasma samples will be analyzed using validated analytical methods in compliance with 
applicable SOPs. 
 
 
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8.6. Biomarkers
Biomarkers are not evaluated in this study.
8.7. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.8. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in an SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
No formal inferential statistics will be applied to the safety data.
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9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis 
Set
Description
Enrolled 
All participants who sign the ICD.
Randomly assigned to 
study intervention
Participants will be randomized to 1 of 6 treatment sequences 
in a 3-way crossover with 3-period design. In Part A, a total of 
18 healthy participants will be enrolled in the study so that 
3 participants will be enrolled in each treatment sequence.
PK Population
The PK concentration population is defined as all enrolled 
participants who received at least 1 dose of abrocitinib and in 
whom at least 1 plasma concentration value is reported.
Taste
All participants who receive at least 1 abrocitinib oral 
suspension formulation for taste evaluation and complete the 
abrocitinib Taste Assessment Questionnaire.
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.
9.3. Statistical Analyses
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints.
9.3.1. Safety Analyses
All safety analyses will be performed on the safety population.
AEs, ECGs, BP, pulse rate, and safety laboratory data will be reviewed and summarized on 
an ongoing basis during the study to evaluate the safety of participants. Any clinical 
laboratory, ECG, BP, and pulse rate abnormalities of potential clinical concern will be 
described. Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
 
 
 
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Medical history and physical examination information, as applicable, collected during the 
course of the study will be considered source data and will not be required to be reported, 
unless otherwise noted. However, any untoward findings identified on physical examinations 
conducted during the active collection period will be captured as AEs, if those findings meet 
the definition of an AE. Data collected at screening that are used for 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.
All safety analyses will be performed on the safety population.
9.3.1.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
The number (%) of participants with maximum postdose QTc values and maximum increases 
from baseline in the following categories will be tabulated by treatment (Table 7): 
Table 7.
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
 
 
 
 
9.3.2.1. Pharmacokinetic Analyses
9.3.2.1.1. Analysis of Population
The PK concentration population is defined as all participants randomized and treated who 
have at least 1 concentration in at least 1 treatment period.
The PK parameter analysis population is defined as all participants randomized and treated 
who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
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9.3.2.1.2. Derivation of Pharmacokinetic Parameters Prior to Analysis
PK parameters for abrocitinib will be derived from the plasma concentrationtime profiles as 
shown in Table 8.
Table 8.
Derivation of PK Parameters
Parameter
Definition
Method of Determination
AUC24
Area under the plasma 
concentration-time profile from time 0
to 24 hours
Linear/Log trapezoidal method.
AUClast
Area under the plasma 
concentration-time profile from time 0
to the time of the last quantifiable 
concentration (Clast)
Linear/Log trapezoidal method.
AUCinfa
Area under the plasma 
concentration-time profile from time 0
extrapolated to infinity 
AUClast + (Clast*/kel),
where Clast* is the predicted plasma concentration 
at the last quantifiable time point estimated from 
the log-linear regression analysis.
Cmax
Maximum plasma concentration
Observed directly from data.
Tmax
Time for Cmax
Observed directly from data as time of first 
occurrence.
t½a
Terminal elimination half-life
Loge(2)/kel,
where kel is the terminal phase rate constant 
calculated by a linear regression of the log-linear 
concentration-time curve. Only those data points 
judged to describe the terminal log-linear decline 
will be used in the regression.
a. If data permit.
Actual PK sampling times will be used in the derivation of PK parameters.
PK parameters in Table 8 will be summarized descriptively by analyte and by treatment, as 
applicable, in accordance with Pfizer Data Standards. Concentrations will be listed and 
summarized descriptively by analyte, nominal PK sampling time and treatment. Individual 
participant and median profiles of the plasma concentration-time data will be plotted by 
treatment using actual and nominal times, respectively. Median profiles will be presented on 
both linear-linear and log-linear scales. 
For the rBA portion of Part A, natural log transformed Abrocitinib AUCinf (if data permit), 
AUClast and Cmax will be analyzed using a mixed effect model with sequence, period and 
treatment as fixed effects and participant within sequence as a random effect. Estimates of 
the adjusted mean differences (Test-Reference) and corresponding 90% CIs will be obtained 
from the model. The adjusted mean differences and 90% CIs for the differences will be 
exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) 
and 90% CIs for the ratios. Treatment A (Abrocitinib tablet) is the Reference Treatment 


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while Treatment B (Abrocitinib suspension) and Treatment C (Abrocitinib tablet + 
famotidine) are the Test Treatments.
For the taste assessment in Part B of the study, the data used in the analysis will be 
transcribed and rescaled to a score from 0 to 100 from the raw measurements on the 
questionnaire. The sensory attributes (overall liking, mouthfeel, bitterness, sourness, 
saltiness, tongue/mouth burn) from the taste questionnaires (Appendix 8) will be listed and 
descriptively summarized by prototype formulation, and question across participants. 
Summary statistics (mean and 90% CI) will be calculated for the various questions. Radar 
plots for each of 4 time points, summarizing all attributes for each treatment will be 
generated. Boxplots of each attribute will be plotted against the time points. 
 
 
9.4. Interim Analyses
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating PK/PD modeling, and/or supporting clinical 
development. 
 
 
 
 
 
 
 
 
 
 
 
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10. SUPPORTING DOCUMENTS AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
•
Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;
•
Applicable ICH GCP guidelines;
•
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
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The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Informed Consent Process
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant and answer all questions regarding the study. The 
participant should be given sufficient time and opportunity to ask questions and to decide 
whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
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The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant.
Participants who are rescreened are required to sign a new ICD.
10.1.3. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.4. Committees Structure
10.1.4.1. Data Monitoring Committee 
This study will not use a DMC.


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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 US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in participants) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted. These 
results are submitted for posting in accordance with the format and timelines set forth by US 
law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
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 DCTs, 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 contribute to the scientific understanding of the 


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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 DCT 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 DCT.
Guidance on completion of DCTs will be provided in the DCT Completion Requirements 
document.
The investigator must ensure that the DCTs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk based initiatives in operations and quality, such as risk management and 
mitigation strategies and analytical risk based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or onsite monitoring), are provided in the integrated quality management 
plan maintained and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.


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When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. 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 DCT or entered in the eDCT 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.
In this study, the DCT will serve as the source document. A document must be available at 
the investigative site that identifies those data that will be recorded on the DCT and for which 
the DCT will be the source document.
Definition of what constitutes source data and its origin can be found in Source Document
Locator, which is maintained by the sponsor’s designee (CRU). Description of the use of the 
computerized system is documented in Source Document Locator, which is maintained by 
the sponsor’s designee (CRU). The investigator must maintain accurate documentation 
(source data) that supports the information entered in the DCT.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the DCT by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.8. 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.


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The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or the ICH GCP 
guidelines;

Inadequate recruitment of participants by the investigator; 

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. 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.


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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 clinical trial management system.
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 
the time of informed consent. The ECC contains, at a minimum, (a) protocol and study 
intervention identifiers, (b) participant’s study identification number, and (c) site emergency 
phone number active 24 hours/day, 7 days per week.
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. 


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10.2. Appendix 2: Clinical Laboratory Tests
The safety laboratory tests listed in Table 12 will be performed at times defined in the SoA of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory; or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety concerns. 
The eGFR will be calculated using the following equation developed by the CKD-EPI which 
utilizes SCr:
CKD-EPI
If female and SCr is ≤0.7 mg/dL:
GFR (mL/min/1.73 m2) = 144 × (SCr/0.7) – 0.329 × 0.993age (× 1.159, if black).
If female and SCr is >0.7 mg/dL:
GFR (mL/min/1.73 m2) = 144 × (SCr/0.7) – 1.209 × 0.993age (× 1.159, if black).
If male and SCr is ≤0.9 mg/dL:
GFR (mL/min/1.73 m2) = 141 × (SCr /0.9) – 0.411 × 0.993age (× 1.159, if black).
If male and SCr is >0.9 mg/dL:
GFR (mL/min/1.73 m2) = 141 × (SCr /0.9) – 1.209 × 0.993age (× 1.159, if black).


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Table 12.
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/urea and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
TBili
Alkaline phosphatase
Uric acid
Albumin
Total protein
eGFR based on the 
CKD-EPI equation
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya

COVID-19 testing

Urine drug screeningb

Pregnancy testc
At screening only:

FSHd

HBsAg

HBcAb

HBsAbe

HCVAb

HIV

QuantiFERON®-TB 
Gold Test
Additional Tests 
(Needed for Hy’s Law)
AST, ALT (repeat)
TBili (repeat)
Albumin (repeat)
Alkaline phosphatase 
(repeat)
Direct bilirubin
Indirect bilirubin
CK
GGT
PT/INR
Total bile acids
Acetaminophen drug 
and/or protein adduct 
levels
a.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
b.
The minimum requirement for drug screening includes cocaine, tetrahydrocannabinol, opiates/opioids, 
benzodiazepines, and amphetamines (others are site specific).
c.
Pregnancy test for female participants of childbearing potential.
d.
For confirmation of postmenopausal status only (only females who are amenorrheic for at least 
12 consecutive months).
e.
HBsAb tested as reflex test only in participants who are HBsAg negative, but are HBcAb positive.
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 DCT.


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Any remaining serum from samples collected for clinical safety laboratory measurements at 
baseline and at all times after dose administration may be retained and stored for the duration 
of the study. Upon completion of the study, these retained safety samples may be used for the 
assessment of exploratory safety biomarkers or unexpected safety findings. These data will 
not be included in the CSR. Samples to be used for this purpose will be shipped to either a 
Pfizer-approved BBS facility or other designated laboratory and retained for up to 1 year 
following the completion of the study.


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.

Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE:

Is associated with accompanying symptoms;

Requires additional diagnostic testing or medical/surgical intervention;

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New condition detected or diagnosed after study intervention administration, even
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/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 an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.
d. Results in persistent or significant disability/incapacity


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
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.
Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or non-pathogenic, is considered serious.  
The event may be suspected from clinical symptoms or laboratory findings indicating 
an infection in a participant exposed to a Pfizer product. The terms “suspected 
transmission” and “transmission” are considered synonymous. These cases are 
considered unexpected and handled as serious expedited cases by pharmacovigilance 
personnel. Such cases are also considered for reporting as product defects, if 
appropriate.
g. Other situations:

Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the DCT and for 
reporting SAEs on the CT SAE Report Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the study intervention under study during pregnancy 
or breastfeeding, and occupational exposure. 
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 DCT. When the same data are collected, the forms must be 


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


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
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE or SAE DCT 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
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.

Moderate: Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL. Instrumental ADL refers to preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc.

Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting self 
care ADL. Self care ADL refers to bathing, dressing and undressing, feeding self, 
using the toilet, taking medications, and not bedridden.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. The investigator will use clinical judgment 
to determine the relationship.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.


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
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/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 
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 DCT, 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 professionals.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology. 


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
New or updated information will be recorded in the originally submitted 
documents.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) 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 
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 and Collection of Pregnancy Information
10.4.1. Male Participant Reproductive Inclusion Criteria
No contraception methods are required for male participants in this study, as the calculated 
safety margin is ≥100-fold between the estimated maternal exposure due to seminal transfer 
and the no-observed-adverse-effect level for serious manifestations of developmental toxicity 
in nonclinical studies.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), as described below, during the intervention period and for at 
least 28 days after the last dose of study intervention, which corresponds to the time 
needed to eliminate any reproductive safety risk of the study intervention(s). If a 
highly effective method that is user dependent is chosen, a second effective method of 
contraception, as described below, must also be used. 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.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;


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
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. 

A 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 (eg, bilateral tubal ligation).
5. Vasectomized partner.

A vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the 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.


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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.
In addition, one of the following effective barrier methods must also be used when 
option 6 or 7 are chosen above:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).


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10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis.

The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or 
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.

The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to study intervention or study interventions of this class to 
understand treatments for the disease(s) under study or the disease(s) themselves.

The results of genetic analyses may be reported in the CSR or in a separate study 
summary or may be used for internal decision making without being included in a 
study report.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained as indicated:

Samples for specified genetic analysis (see Section 8.5.1) will be stored for a 
period of up to 3 years after regulatory approval.

Retained samples (see Section 8.5.2) will be stored indefinitely or for another
period as per local requirements.

Participants may withdraw their consent for the storage and/or use of their Retained 
Research Samples at any time by making a request to the investigator; in this case, 
any remaining material will be destroyed. Data already generated from the samples 
will be retained to protect the integrity of existing analyses.

Samples for genetic research will be labeled with a code. The key between the code 
and the participant’s personally identifying information (eg, name, address) will be 
held securely at the study site. 


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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors”. In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are 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 (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 sample 
for acetaminophen 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 premature ventricular complexes, triplets, or short intervals 
(<30 seconds) of consecutive ventricular complexes.
ECG Findings That May Qualify as SAEs

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia. 

Asystole:

In awake, symptom-free participants in sinus rhythm, with documented periods 
of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node. 

In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).


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


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10.8. Appendix 8: Taste Assessment Questionnaire
1. Questionnaire should be administered to adult participants, preferably by the trained 
staff. The clinical staff is trained by the CRU clinical coordinator for performing the 
taste questionnaire and regarding the specific study restrictions.
2. Use colored copy of the questionnaire.
3. Do not alter (reduce or enlarge) the original size of the questionnaire.
4. Please gather the following background information: 
Background Information
Study #/Study Site
Period and Day
Participant ID (Rand ID)
Formulation ID
Collection Date
Collection Time
Name of trained staff
Questionnaire fully completed
Yes/No


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Example: How to provide a mark (Ï) on the color bar

Good (score = 0)
Bad (score = 100)


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10.9. Appendix 9: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term

ongoing/continuous event
Abs
absolute
AD
atopic dermatitis
AE
adverse event
AIA
adjuvant-induced arthritis
ALT
alanine aminotransferase
ARA
acid-reducing agent
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AUC
area under the curve
AUC24
area under the concentration-time curve from time 0 to 24 hours
AUCinf
area under the plasma concentration-time curve from time 
0 extrapolated to infinity
AUClast
area under the concentration-time curve from 0 to the time of last 
measurement
AUCtau
AUC from time 0 to time tau, the dosing interval
AV
atrioventricular
BA
bioavailability
BBS
Biospecimen Banking System
BCRP
breast cancer resistance protein
BID
twice daily
BLQ
below the limit of quantification
BMI
body mass index
BP
blood pressure
BUN
blood urea nitrogen
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CL/F
apparent clearance
Cmax
maximum observed concentration
CO2
carbon dioxide (bicarbonate)
COVID-19
coronavirus disease 2019
CRO
Contract Research Organization
CRU
Clinical Research Unit
CSR
Clinical Study Report
CT
clinical trial


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Abbreviation
Term
CYP
cytochrome P450
DAI
Dosing Administration Instructions
DC
discontinuation
DCT
data collection tool
DDI
drug-drug interaction 
DILI
drug-induced liver injury
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram
eDCT
electronic data collection tool
EDB
exposure during breastfeeding
EDP
exposure during pregnancy
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration 
FIH
first-in-human
FOB
functional observational battery
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GERD
gastroesophageal reflux disease
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
GLP
Good Laboratory Practice
H2
histamine-2
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen
HCVAb
hepatitis C antibody
HDPE
High Density Poly Ethylene
hERG
human ether-á-go-go-related gene
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
IC50
50% inhibitory concentration
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identity


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Abbreviation
Term
IFN
interferon
IFN-α
interferon-alpha
IFN-γ
interferon-gamma
IL
interleukin
IND
investigational new drug 
INR
international normalized ratio
IPAL
Investigational Product Accountability Log
IR
immediate release
IRB
institutional review board
IV
intravenous
JAK
janus kinase
K2EDTA
potassium ethylenediaminetetraacetic acid
Kel
first-order elimination rate constant
KDR
kinase insert domain receptor
LFT
liver function test
MAO-A
monoamine oxidase A
MATE
multidrug and toxin extrusion protein
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDR
medical device regulation
mRNA
message ribonucleic acid
N/A
not applicable
NADPH
nicotinamide adenine dinucleotide phosphate
NOAEL
no-observed-adverse-effect level
OAT
organic anion transporter
OATP
for organic anion transporting polypeptide
OCT
organic cation transporter
PBMC
peripheral blood mononuclear cells
PCR
Polymerase Chain Reaction
PCRU
Pfizer Clinical Research Unit
PD
pharmacodynamic(s)
PEER
Pediatric Eczema Elective Registry
P-gp
P-glycoprotein
pH
negative logarithm of hydrogen ion concentration
PI
principal investigator
PK
pharmacokinetic(s)
POC
proof-of-concept
PPI
proton pump inhibitors
PT
prothrombin time
CCI


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Abbreviation
Term
QD
once daily
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
Rac
accumulation ratio
rBA
relative BA
RBC
red blood cell
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome 
SCr
serum creatinine
SGOT
serum glutamic oxaloacetic transaminase
SGPT
serum glutamic pyruvic transaminase
SoA
schedule of activities
SOC
System Organ Class
SOP
standard operating procedure
SRSD
single reference safety document
STAT
signal transducers and activators of transcription
SULT
sulfotransferase
SUSAR
suspected unexpected serious adverse reaction
t½
apparent terminal half-life
TB
tuberculosis
TBili
total bilirubin
TEAE
treatment emergent AE
Tmax
time to maximum concentration
TSLP
thymic stromal lymphopoietin
TYK
tyrosine kinase
UGT
uridine diphospho-glucuronosyltransferase
ULN
upper limit of normal
US
United States
Vc/F
apparent central volume of distribution
VEGFR
vascular endothelial growth factor receptor
Vp/F
apparent peripheral volume of distribution
WBC
white blood cell
WOCBP
woman/women of childbearing potential


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Investigator’s Brochure, Abrocitinib (PF-04965842). Apr 2020.
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Leicht S, Hanggi M. Atopic dermatitis. How to incorporate advances in management. 
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Margolis JS, Abuabara K, Bilker W, et al. Persistence of mild to moderate atopic 
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Slater NA, Morrell DS. Systemic therapy of childhood atopic dermatitis. Clin Dermatol.
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Kent JD, Holt RJ, Jung D, et al. Pharmacodynamic evaluation of intragastric pH and 
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SAP_001.pdf: