Clinical trial NCT05852340
Conditions: Healthy Volunteers Adult Pharmacokinetics
Keywords: Adult Pharmacokinetic
Sponsor: Pfizer
Start date: 2023-05-09; Completion date: 2023-07-24
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to compare if two forms of study medicine, Ritlecitinib, get processed differently in healthy adults.

This study is seeking participants who are:

* aged 18 or older;
* male or female who are healthy as determined by medical assessment ;
* Body-mass Index (BMI) of 16 to 32, and a total body weight \> 45kg.

The study will take up to 2.5 months, including the screening period. There will be 5 periods in total for this study. Participants will have to stay at the study clinic for at least 11 days. Participants will take Riltecitinib either as sprinkled in Soft Food or as Intact Blend-In Capsule. On day 1 of each period, participants will take Riltecitinib and have blood samples taken both before and afterwards. Participants will also answer questions for taste assessment purpose. A follow-up phone call will be made at 28 to 35 days after the last study period.

Detailed description:
Ritlecitinib is a covalent and irreversible inhibitor of JAK3 with high selectivity over the other JAK isoforms (JAK1, JAK2, and TYK2). Ritlecitinib also inhibits irreversibly the tyrosine kinase expressed in TEC family kinases with selectivity over the broader human kinome. Treatment with ritlecitinib is expected to inhibit the inflammatory pathways mediated by IL 7, IL 15 and IL 21, all implicated in UC, CD, AA, RA, and vitiligo. Moreover, due to lack of activity against the other JAK isoforms, ritlecitinib is expected to spare immunoregulatory cytokines such as IL 10, IL 27 and IL 35, which are critical to the maintenance of immunosuppressive functions and immune homeostasis.

The objective of this study is to estimate the impact of administration methods on the bioavailability of the pediatric ritlecitinib intact BiC formulation. The study will be conducted as a Phase 1, open-label, single dose, randomized, 4-crossover periods and 1-fixed period design in a single cohort of approximately 12 healthy male or female participants at a single center. Participants will be randomized into 1 of 4 sequences of treatment. Blood samples will be collected for PK analysis. A taste assessment will be also conducted.

Participants will participate in the study for up to approximately 2.5 months, with the inclusion of the screening and follow-up period. On Day 1 of each period, participants will receive a single dose of IP. Administration of IP will be via dosing using intact BiCs with water or by emptying the capsule contents on soft food as per dosing instructions.

Participants will be confined in the CRU for a total of at least 11 days and discharged at the discretion of the investigator. A follow-up phone call will be made at least 28 calendar days and up to 35 calendar days after the last administration of the study intervention to capture any potential AE and confirm appropriate contraceptive usage.

Tolerability and safety will be assessed for all treatments by monitoring AEs.

Arms: arm 1: ritlecitinib 1 x 30 milligram (mg) intact blend-in-capsule (BiC) in fasted state arm 2: contents of ritlecitinib 1 x 30 mg intact BiC sprinkled on strawberry jam in fasted state arm 3: contents of ritlecitinib 1 x 30 mg intact BiC sprinkled on yoghurt in fasted state arm 4: contents of ritlecitinib 1 x 30 mg intact BiC sprinkled on applesauce in fasted state arm 5: ritlecitinib 1 x 30 mg intact BiC given with high fat meal
Interventions: intervention 1: Ritlecitinib
Intervention descriptions: intervention 1: ritlecitinib 1 x 30 mg intact BiC (Treatment Arms A, E)

ritlecitinib 1 x 30 mg intact BiC sprinkled on soft foods (Treatment Arms B, C, D)

Protocol documents:
Prot_000.pdf: 
Ritlecitinib (PF-06651600)
Protocol B7981078
Final Protocol, 02 Feb 2023
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A PHASE 1, RANDOMIZED, OPEN-LABEL, CROSSOVER STUDY TO ESTIMATE
THE RELATIVE BIOAVAILABILITY OF PEDIATRIC RITLECITINIB
(PF-06651600) SPRINKLED IN APPLESAUCE, YOGHURT AND STRAWBERRY 
JAM RELATIVE TO INTACT BLEND-IN CAPSULE OF RITLECITINIB AND THE 
EFFECT OF FOOD ON THE BIOAVAILABILITY OF THE INTACT BLEND-IN
CAPSULE DOSAGE FORMULATION OF RITLECITINIB IN HEALTHY ADULT 
PARTICIPANTS
Study Intervention Number:
PF-06651600
Study Intervention Name:
Ritlecitinib 
US IND Number:
131503
EudraCT Number:
2022-502872-22-00
ClinicalTrials.gov ID:  
NA
Pediatric Investigational Plan Number:
NA
Protocol Number:
B7981078
Phase:
1
Brief Title: A Phase 1 Study Evaluating Relative Bioavailability of Sprinkled 
Ritlecitinib in Applesauce, Yoghurt, and Strawberry Jam and Evaluating the Effect of 
Food on the Bioavailability of Ritlecitinib Intact Blend-In Capsule in Healthy Adult 
Participants
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.


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Document History
Document
Version Date
Original protocol
02 Feb 2023


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................15
1.3. Schedule of Activities .............................................................................................16
2. INTRODUCTION ...............................................................................................................21
2.1. Study Rationale .......................................................................................................21
2.2. Background .............................................................................................................21
2.2.1. Nonclinical Pharmacology..........................................................................21
2.2.2. Nonclinical Pharmacokinetics and Metabolism .........................................21
2.2.3. Nonclinical Safety ......................................................................................21
2.2.4. Clinical Overview.......................................................................................21
2.2.4.1. Clinical Overview of Ritlecitinib..............................................21
2.2.4.2. Pharmacokinetic Overview of Ritlecitinib................................22
2.2.4.3. Safety Overview of Ritlecitinib.................................................22
2.3. Benefit/Risk Assessment.........................................................................................27
2.3.1. Risk Assessment.........................................................................................29
3. OBJECTIVES AND ENDPOINTS.....................................................................................30
4. STUDY DESIGN.................................................................................................................30
4.1. Overall Design.........................................................................................................30
4.2. Scientific Rationale for Study Design.....................................................................32
4.2.1. Choice of Contraception/Barrier Requirements .........................................32
4.2.2. Collection of Retained Research Samples..................................................32
4.3. Justification for Dose ..............................................................................................32
4.4. End of Study Definition ..........................................................................................32
5. STUDY POPULATION......................................................................................................32
5.1. Inclusion Criteria.....................................................................................................33
5.2. Exclusion Criteria....................................................................................................33
5.3. Lifestyle Considerations..........................................................................................37
5.3.1. Contraception..............................................................................................37
5.3.2. Meals and Dietary Restrictions...................................................................38


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5.3.3. Caffeine, Alcohol, and Tobacco .................................................................38
5.3.4. Activity .......................................................................................................39
5.3.5. Vaccination.................................................................................................39
5.4. Screen Failures ........................................................................................................40
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................40
6.1. Study Intervention(s) Administered........................................................................40
6.1.1. Administration............................................................................................41
6.2. Preparation, Handling, Storage, and Accountability...............................................42
6.2.1. Preparation and Dispensing........................................................................43
6.3. Assignment to Study Intervention...........................................................................43
6.4. Blinding...................................................................................................................43
6.4.1. Blinding of Participants..............................................................................43
6.4.2. Blinding of Site Personnel..........................................................................44
6.4.3. Blinding of the Sponsor..............................................................................44
6.5. Study Intervention Compliance...............................................................................44
6.6. Dose Modification...................................................................................................44
6.7. Continued Access to Study Intervention After the End of the Study......................44
6.8. Treatment of Overdose............................................................................................44
6.9. Prior and Concomitant Therapy..............................................................................45
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................45
7.1. Discontinuation of Study Intervention ....................................................................45
7.1.1. Liver Injury.................................................................................................46
7.1.2. Potential Cases of Acute Kidney Injury .....................................................46
7.1.3. Pregnancy ...................................................................................................46
7.2. Participant Discontinuation/Withdrawal From the Study.......................................47
7.2.1. Withdrawal of Consent...............................................................................47
7.3. Lost to Follow-up....................................................................................................48
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................48
8.1. Administrative Procedures ......................................................................................48
8.1.1. Baseline Procedures....................................................................................49
8.2. Efficacy Assessments..............................................................................................49


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Protocol B7981078
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8.3. Safety Assessments .................................................................................................49
8.3.1. Physical Examinations................................................................................49
8.3.2. Vital Signs ..................................................................................................50
8.3.2.1. Blood Pressure and Pulse Rate..................................................50
8.3.2.2. Temperature ..............................................................................50
8.3.3. Electrocardiograms.....................................................................................50
8.3.4. Clinical Safety Laboratory Assessments ....................................................51
8.3.5. COVID-19 Specific Assessments...............................................................52
8.3.6. Pregnancy Testing ......................................................................................52
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................52
8.4.1. Time Period and Frequency for Collecting AE and SAE Information.......53
8.4.1.1. Reporting SAEs to Pfizer Safety...............................................53
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF...................54
8.4.2. Method of Detecting AEs and SAEs ..........................................................54
8.4.3. Follow-Up of AEs and SAEs......................................................................54
8.4.4. Regulatory Reporting Requirements for SAEs...........................................54
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................55
8.4.5.1. Exposure During Pregnancy......................................................55
8.4.5.2. Exposure During Breastfeeding ................................................56
8.4.5.3. Occupational Exposure .............................................................57
8.4.6. Cardiovascular and Death Events...............................................................57
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................57
8.4.8. Adverse Events of Special Interest.............................................................57
8.4.8.1. Lack of Efficacy........................................................................57
8.4.9. Medical Device Deficiencies......................................................................57
8.4.10. Medication Errors.....................................................................................57
8.5. Pharmacokinetics ....................................................................................................58
8.6. Genetics...................................................................................................................60
8.6.1. Specified Genetics ......................................................................................60
8.6.2. Retained Research Samples for Genetics ...................................................60
8.7. Biomarkers ..............................................................................................................60


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8.7.1. Retained Research Samples for Biomarkers...............................................60
8.8. Immunogenicity Assessments.................................................................................60
8.9. Health Economics ...................................................................................................60
9. STATISTICAL CONSIDERATIONS ................................................................................61
9.1. Statistical Hypotheses .............................................................................................61
9.2. Analysis Sets ...........................................................................................................61
9.3. Statistical Analyses .................................................................................................61
9.3.1. Efficacy Analyses .......................................................................................61
9.3.2. Safety Analyses ..........................................................................................61
9.3.3. Pharmacokinetic Analyses..........................................................................62
9.4. Interim Analyses .....................................................................................................63
9.5. Sample Size Determination.....................................................................................63
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................65
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............65
10.1.1. Regulatory and Ethical Considerations ....................................................65
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................65
10.1.2. Financial Disclosure .................................................................................66
10.1.3. Informed Consent Process ........................................................................66
10.1.4. Data Protection .........................................................................................67
10.1.5. Committees Structure ...............................................................................67
10.1.6. Dissemination of Clinical Study Data ......................................................68
10.1.7. Data Quality Assurance ............................................................................69
10.1.8. Source Documents....................................................................................70
10.1.9. Study and Site Start and Closure ..............................................................70
10.1.10. Publication Policy...................................................................................71
10.1.11. Sponsor’s Medically Qualified Individual..............................................72
10.2. Appendix 2: Clinical Laboratory Tests .................................................................73
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................74
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10.3.1. Definition of AE .......................................................................................74
10.3.2. Definition of an SAE ................................................................................75
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................77
10.3.4. Reporting of SAEs....................................................................................80
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................82
10.4.1. Male Participant Reproductive Inclusion Criteria....................................82
10.4.2. Female Participant Reproductive Inclusion Criteria.................................82
10.4.3. Woman of Childbearing Potential. ...........................................................82
10.4.4. Contraception Methods.............................................................................83
10.5. Appendix 5: Genetics............................................................................................85
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .......86
10.7. Appendix 7: Kidney Safety: Monitoring Guidelines ............................................88
10.7.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury..............................................................................88
10.7.2. Age-Specific Kidney Function Calculation Recommendations...............88
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI 
Equations ...........................................................................................88
10.7.3. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities...................................................................................................88
10.8. Appendix 8: ECG Findings of Potential Clinical Concern ...................................89
10.10. Appendix 10: Abbreviations ...............................................................................99
11. REFERENCES ................................................................................................................103
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Protocol B7981078
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LIST OF TABLES
Table 1.
Study Schedule of Assessment.................................................................16
Table 2.
Pharmacokinetic Sampling Schema for Each Period ...............................20
Table 3.
Study Design and Treatments...................................................................31
Table 4.
Definitions of PK Parameters...................................................................62
Table 5.
Protocol Required Safety Laboratory Assessments..................................73


Ritlecitinib (PF-06651600)
Protocol B7981078
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: A Phase 1, Randomized, Open-label, Crossover Study to Estimate the 
Relative Bioavailability of Pediatric Ritlecitinib Sprinkled in Applesauce, Yoghurt and 
Strawberry Jam Relative to Intact Blend-In Capsule of Ritlecitinib and the Effect of Food on 
the Bioavailability of the Intact Blend-In Capsule Dosage Formulation of Ritlecitinib in 
Healthy Adult Participants.
Brief Title: A Phase 1 Study Evaluating Relative Bioavailability of Sprinkled Ritlecitinib in 
Applesauce, Yoghurt, and Strawberry Jam and Evaluating the Effect of Food on the 
Bioavailability of Ritlecitinib Intact Blend-In Capsule in Healthy Adult Participants.
Regulatory Agency Identification Number(s):
US IND Number:
131503
EudraCT Number:
2022-502872-22-00
ClinicalTrials.gov ID:  
NA
Pediatric Investigational Plan Number:
NA
Protocol Number:
B7981078
Phase:
1
Rationale:
Ritlecitinib is a covalent and irreversible inhibitor of JAK3 with high selectivity over the 
other JAK isoforms (JAK1, JAK2, and TYK2).  Ritlecitinib also inhibits irreversibly the 
TEC family kinases with selectivity over the broader human kinome.  Treatment with 
ritlecitinib is expected to inhibit the inflammatory pathways mediated by IL-7, IL-15 and 
IL-21, all implicated in UC, CD, AA, RA, and vitiligo.  Moreover, due to lack of activity 
against the other JAK isoforms, ritlecitinib is expected to spare immunoregulatory cytokines 
such as IL-10, IL-27 and IL-35, which are critical to the maintenance of immunosuppressive 
functions and immune homeostasis.
The objective of this study is to estimate the impact of administration methods on the 
bioavailability of the pediatric ritlecitinib intact BiC formulation. 
Objectives and Endpoints:
Objectives
Endpoints
Primary: 
Primary:
To estimate the relative BA of ritlecitinib BiC when 
sprinkled on food (apple sauce, strawberry jam, and 
Plasma AUCinf and Cmax of ritlecitinib.




Ritlecitinib (PF-06651600)
Protocol B7981078
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Study Population:
Key inclusion and exclusion criteria are listed below:
Inclusion Criteria 
Participants must meet the following key inclusion criteria to be eligible for enrollment into 
the study:
1. Participants aged 18 or older (or the minimal age of consent in accordance with 
location regulations) at screening. 
2. Male and female participants who are healthy as determined by medical evaluation 
including a detailed medical history, full physical examination (which includes BP 
and pulse rate measurement), clinical laboratory tests, and 12-lead ECG.
3. BMI of 16 to 32 kg/m2, and a total body weight >45 kg (99 lb).
4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
5. Capable of giving signed informed consent.
Exclusion Criteria 
Participants with any of the following characteristics/conditions will be excluded:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease.
2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). 
3. Known immunodeficiency disorder, including positive serology for HIV, or a first 
degree relative with a hereditary immunodeficiency.
4. Infection with hepatitis B or hepatitis C viruses according to protocol specific testing 
algorithm history.
5. Participants with any of the specified acute or chronic infections or infection history.
6. History of febrile illness within 5 days prior to the first dose of study intervention.
7. History of any lymphoproliferative disorder such as EBV related lymphoproliferative 
disorder, history of lymphoma, history of leukemia, or signs or symptoms suggestive 
of current lymphatic or lymphoid disease.




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Protocol B7981078
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Participants will be confined in the CRU for a total of at least 11 days and discharged at the 
discretion of the investigator. A follow-up phone call will be made at least 28 calendar days 
and up to 35 calendar days after the last administration of the study intervention to capture 
any potential AE and confirm appropriate contraceptive usage.
Tolerability and safety will be assessed for all treatments by monitoring AEs.
Statistical Methods:
The following table presents the widths of 90% confidence interval for different estimated 
effects in 12 participants:
Parameter
Estimated Effect
(100*Test/Reference)
90% CI
CI Width
AUC
85%
77.75% to 92.92%
  15.17%
90%
82.33% to 98.39%
             16.06%
95%
86.9% to 103.85%
             16.95%
100%
91.47% to 109.32%
17.85%
105%
96.05% to 114.79%
18.74%
110%
100.62% to 120.25%
19.63%
115%
105.20% to 125.72%
20.52%
Cmax
85%
71.56% to 100.97%
29.41%
90%
75.77% to 106.91%
31.14%
95%
     79.98% to 112.84%
32.87%
100%
     84.19% to 118.78%
34.60%
105%
88.40% to 124.72%
36.33%
110%
92.60% to 130.66%
38.06%
115%
     96.81% to 136.60%
39.79%
These calculations are based on the estimates of within-participants standard deviations of 
0.117 and 0.226 for logeAUCinf and logeCmax, respectively, as obtained from studies 
B7981022, B7981029, and B7981030. 
Natural log transformed AUCinf (if data permit), AUClast and Cmax will be analyzed using a 
mixed effects 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% confidence intervals will be obtained from the model.  
The adjusted mean differences and 90% confidence intervals for the differences will be 
exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) 
and 90% confidence intervals for the ratios. Treatment A (pediatric capsules, fasted) will be 
the Reference treatment and Treatments B-D (pediatric capsules sprinkled in strawberry jam, 
pediatric capsules sprinkled in yoghurt, and pediatric capsules sprinkled in applesauce) will 
be the Test treatments.
Natural log transformed AUCinf (if data permit), AUClast and Cmax will be analyzed using a 
mixed effects model with sequence and treatment as fixed effects and participant within 
sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) 
and corresponding 90% confidence intervals will be obtained from the model.  The adjusted 
mean differences and 90% confidence intervals for the differences will be exponentiated to 




Ritlecitinib (PF-06651600)
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1.2. Schema










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Table 2.
Pharmacokinetic Sampling Schema for Each Period
Visit Identifier 
Notes
Study Day
1
2
Hours After Dose
0
0.25
0.5
1
1.5
2
3
4
6
9
12
24

Hour 0 = predose PK 
samples collection. Any 
time prior to dosing 
ritlecitinib on the day of 
dosing.
Study intervention administration
X
PK blood sampling
X
X
X
X
X
X
X
X
X
X
X
X

Ritlecitinib PK blood 
samples (2 mL blood to 
yield approximately 0.5 
mL plasma) are to be 
collected.
PK blood collection Micro-sampling
X
X
X
X
X
X

Additional PK blood
samples collection using 
Tasso device, as 
explained in Section 8.5
only for the Treatment A 
arm.


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2. INTRODUCTION
Ritlecitinib is a selective covalent inhibitor of JAK3 and the TEC family kinases and is 
currently under development for the treatment of AA, RA, vitiligo, UC, and CD.
2.1. Study Rationale 
The Study B7981078 is being conducted to estimate the impact of administration methods on 
the bioavailability of pediatric ritlecitinib BiC. 
2.2. Background 
Ritlecitinib is a covalent and irreversible inhibitor of JAK3 with high selectivity over the 
other JAK isoforms (JAK1, JAK2, and TYK2). Ritlecitinib also inhibits irreversibly the 
tyrosine kinase expressed in TEC family kinases with selectivity over the broader human 
kinome.  Treatment with ritlecitinib is expected to inhibit the inflammatory pathways 
mediated by IL-7, IL-15 and IL-21, all implicated in UC, CD, AA, RA, and vitiligo.  
Moreover, due to lack of activity against the other JAK isoforms, ritlecitinib is expected to 
spare immunoregulatory cytokines such as IL-10, IL-27 and IL-35, which are critical to the 
maintenance of immunosuppressive functions and immune homeostasis.
2.2.1. Nonclinical Pharmacology
Details of the nonclinical pharmacology of ritlecitinib can be found in the current IB.
2.2.2. Nonclinical Pharmacokinetics and Metabolism
Details of the nonclinical PK and metabolism of ritlecitinib can be found in the current IB.
2.2.3. Nonclinical Safety
The NOAELs in the 6-month rat and second 9-month dog toxicity studies were 200 and 
10 mg/kg/day, respectively. These exposures represent 50-fold exposure multiple in the rat 
study and a 7.4-fold exposure multiple in the dog study relative to the clinical dose of 50 mg. 
In the second 9-month dog toxicity study, the NOAEL of 10 mg/kg/day was based on 
adverse overimmunosuppression and axonal dystrophy (not axonal degeneration) in the CNS
and the PNS at ≥20 mg/kg/day, accompanied by functional auditory deficits (BAEP) at the 
highest dose of 40 mg/kg/day (a 33-fold exposure multiple relative to the clinical dose of 
50 mg).
Further information is available in the current version of the ritlecitinib IB. 
2.2.4. Clinical Overview
2.2.4.1. Clinical Overview of Ritlecitinib
As of 30 May 2022, 26 clinical studies with ritlecitinib have been completed (22 Phase 1 
studies in healthy participants or special populations and 6 Phase 2 or Phase 3 studies in 
participants with RA, AA, UC or vitiligo). A total of 464 participants were exposed to 
ritlecitinib in the Phase 1 healthy participant and special population studies. In completed and 


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ongoing interventional Phase 2 and Phase 3 studies in AA and vitiligo, 1628 participants 
have received ritlecitinib. 
2.2.4.2. Pharmacokinetic Overview of Ritlecitinib
The PK profile of ritlecitinib is characterized by rapid absorption, rapid elimination (t½
ranging from 1.3 to 2.3 hours) and are approximately dose proportional. Following multiple 
oral doses, steady-state was reached approximately by Day 4 due to non-stationary PK.
Ritlecitinib has been evaluated at single oral doses ranging from 5 mg to 800 mg and 
multiple oral doses ranging from 50 mg to 400 mg QD and at 100 mg and 200 mg BID for 
14 days. The clearance mechanisms for ritlecitinib in humans are primarily by metabolism, 
with approximately 4% of the dose excreted as unchanged drug in urine.
2.2.4.2.1. Effect of Food on PK of Ritlecitinib 
Overall, food does not have a clinically significant impact on the systemic exposures of 
ritlecitinib and the product may be administered regardless of food intake. The 
coadministration of a 100 mg ritlecitinib capsule with a high-fat meal reduced the ritlecitinib 
Cmax by ~32% with no impact on extent of ritlecitinib absorbed as the AUCinf increased by a 
marginal amount of 11%. In clinical studies, ritlecitinib was administered without regard to 
meals.
In Study B7981003 (Module 5.3.1.1 B7981003 CSR), the co-administration of a single 50 
mg tablet with a high-fat breakfast reduced Cmax by ~39%, with no meaningful change in 
AUCinf and a slight increase in Tmax.
In Study B7981029 (Module 5.3.1.2 B7981029 CSR), the co-administration of a single 100 
mg capsule with a high-fat breakfast reduced Cmax by ~32% with no meaningful change in 
AUCinf and a slight increase in Tmax.
On the basis of the consistency of the PK results from B7981003 and B7981029 and dosing 
without regard to food in B7981015 Phase 2b/3 trial, ritlecitinib may be administered with or 
without food. 
2.2.4.3. Safety Overview of Ritlecitinib
2.2.4.3.1. Studies in Healthy Participants
In 22 healthy volunteer studies, ritlecitinib was found to be well tolerated and to have an 
acceptable safety profile.
Additional single dose 2- or 3-way crossover studies were performed to examine drug 
interactions (B7981017, B7981018, B7981023), food effect and relative bioavailability 
(B7981003) of ritlecitinib. Each study included 12 to 14 healthy participants.
In all the above studies, ritlecitinib was found to be well tolerated and to have an acceptable 
safety profile.
The current IB should be referred to for more detailed information.


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2.2.4.3.2. Phase 2a Study in Rheumatoid Arthritis
The completed Phase 2a study B7981006 was an 8-week randomized, double-blind, 
placebo-controlled, parallel-group, multicenter study in participants with moderate-to-severe
active RA with an inadequate response to methotrexate.  A total of 70 participants were 
randomized to study treatment; 28 participants received placebo and 42 participants received 
ritlecitinib 200 mg QD.  Participants remained on stable background arthritis therapy, which 
had to include methotrexate (supplemented with folic/folinic acid per the local treatment 
guidelines).
Ritlecitinib was determined to be generally safe and well tolerated in this study.  There were 
no deaths or SAEs.  TEAEs were numerically higher in participants receiving ritlecitinib 
compared to those receiving placebo. The majority of the AEs were mild in severity.  
Overall, the most frequently reported treatment-related TEAE was Lymphopenia (2 [2.9%] 
participants in total: 2 [4.8%] participants in the ritlecitinib group and 0 participants in the 
placebo group). A total of 3 participants (7.1%) in the ritlecitinib group and 0 participants in 
the placebo group permanently discontinued due to TEAEs. One (1) participant discontinued 
due to suicidal ideation, 1 participant discontinued due to lymphopenia, and the third 
participant discontinued due to hepatotoxicity. There were no SAE and no deaths among 
participants who participated in Study B7981006. 
2.2.4.3.3. Phase 2a Studies in Alopecia Areata
Study B7931005 is a completed Phase 2a, double-blind, placebo-controlled, multicenter 
study to evaluate the efficacy and safety profile of ritlecitinib (200 mg for 4 weeks, followed 
by 50 mg for 20 weeks) and brepocitinib in participants with moderate to severe AA. The 
study consists of the initial 24-week double-blind treatment period, an up to 12-month 
single-blind extension period, and a 6-month crossover open-label extension period. A total 
of 142 participants were randomized to study treatment, among whom 47 participants 
received placebo and 48 participants received ritlecitinib.
During the initial 24-week treatment period of Study B7931005, there were no deaths and no 
participant in the ritlecitinib treatment group experienced a SAE. The most
frequently (≥5%) reported all causalities TEAEs were Nasopharyngitis and Headache (12.5%
each), Acne (10.4%), Diarrhoea and Upper respiratory tract infection (8.3% each), Dermatitis
atopic, Folliculitis, and Nausea (6.3% each). The majority of treatment-related TEAEs (67 
out of 84) were mild. The most commonly reported treatment-related TEAEs for ritlecitinib 
by preferred term were upper respiratory tract infection (6.3%), and acne, nausea, and 
headache (each at 4.2%). Two participants discontinued ritlecitinib due to AEs and continued 
in the study; the AEs were angioedema and blood creatine phosphokinase increased. A total 
of 5 participants had a temporary discontinuation of study drug due to AEs. All these AEs 
resolved and were mild in severity. 
There were no SAEs or deaths reported with ritlecitinib in Study B7931005.
In addition to the initial 24-week period, the trial included two extensions. There were no 
serious infections, adverse events of QTcF prolongation, malignancies and/or no case of 
herpes zoster during the extension periods.




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2.2.4.3.5. Phase 2b Study in vitiligo
Study B7981019 is a completed Phase 2b, randomized, double blind, parallel group, 
multicenter, placebo controlled, dose ranging study to investigate different doses of 
ritlecitinib with a partial blinded extension period to evaluate the efficacy and safety of 
ritlecitinib in active non-segmental vitiligo. 
In the 24-week double-blind dose ranging (DR) Treatment Period, participants were 
randomized to 1 of 5 treatment groups (2 groups with a ritlecitinib induction dose of 200 mg 
QD or 100 mg QD for 4 weeks followed by maintenance dosing of 50 mg QD for 20 weeks, 
and 3 groups with 50 mg QD, 30 mg QD, and 10 mg QD ritlecitinib dosing for 24 weeks) or 
matching placebo. There were 6 groups with QD dosing in the Extension Period of 24 weeks: 
ritlecitinib induction dosing of 200 mg for 4 weeks followed by maintenance dosing of 50 
mg for 20 weeks (open-label); 3 groups with induction dosing of 200 mg for 4 weeks 
followed by maintenance dosing of 50 mg for 20 weeks, 50 mg for 24 weeks, and 30 mg for 
24 weeks (blinded); brepocitinib only (induction dosing of 60 mg for 4 weeks followed by 
maintenance dosing of 30 mg for 16 weeks [open-label]); observation-only (no treatment) 
group (open-label).
In the DR treatment period, of the 364 treated participants (298 treated with ritlecitinib), 66 
(18.1%) discontinued from study intervention, of whom 11 received placebo treatment.
Across treatment groups, the proportion of participants who discontinued study intervention 
ranged from 13.4% (100/50 mg) to 28.0% (30 mg). The primary reason for discontinuation 
from study intervention was withdrawal by participant (29 [8.0%]). There were 19 (5.2%) 
participants who discontinued study intervention due to AEs: 2 (3.1) in 200/50 mg, 4 (6.0) in 
100/50 mg, 5 (7.5) in 50 mg, 2 (4.0) in 30 mg, 3 (6.1) in 10 mg and 3 (4.5) in placebo. In the 
Extension Period, there were 7 ritlecitinib treated participants who discontinued study 
intervention due to AEs.
The majority of all-causality TEAEs in participants across treatment groups in both treatment 
periods were mild or moderate in severity. There were 277 (76.1%) participants with 756 all 
causality TEAEs in the DR Period. The most frequently reported all-causality TEAEs were 
nasopharyngitis (15.9%), URTI (11.5%), and headache (8.8%). There were 126 (34.6%) 
participants with 195 treatment-related AEs. The most frequently reported treatment-related 
TEAEs were nasopharyngitis (4.1%), diarrhea (1.9%), and headache (1.9%). The majority of 
treatment-related TEAEs across treatment groups were mild or moderate in severity, and the 
number of severe events was not dose-dependent.
In the DR period, SAEs were reported in 4 participants (migraine in 50 mg, esophageal 
spasm in 30 mg, migraine in 10 mg, neurogenic bladder in placebo). All events were assessed 
as unrelated to the study intervention and the participants recovered. No SAEs were reported 


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in the 200/50 mg or 100/50 mg groups. One SAE (uterine leiomyoma, assessed as unrelated) 
was reported in the Extension Period.
There were no clinically meaningful trends for hematology, lipids, or chemistry lab
parameters in participants treated with ritlecitinib.
2.2.4.3.6. Phase 2b/3 Study in Alopecia Areata 
B7981015 was a Phase 2b/3, randomized, double-blind, placebo-controlled, dose-ranging 
study to investigate ritlecitinib in participants with ≥50% scalp hair loss due to AA. The 
study had a maximum duration of approximately 57 weeks. This included an up to 5-week 
Screening period, a 48-week treatment period, and a 4-week follow-up period (for 
participants who did not roll over into the open-label, long-term Study B7981032). The 
treatment period was comprised of a placebo-controlled period that included a 4-week 
loading phase and a 20-week maintenance phase, followed by a 24-week extension phase. 
The study completed enrollment with a total of 718 participants. Eligible participants were 
randomized to blinded ritlecitinib and matching placebo in a 2:2:2:2:1:1:1 (200 mg/50 mg, 
200 mg/30 mg, 50 mg, 30 mg, 10 mg, placebo-200 mg/50 mg, and placebo-50 mg, 
respectively) manner for a total of 7 treatment sequences. 
A total of 1097 participants were screened and 718 participants were randomized to 
treatment. Of these, 715 (99.6%) received treatment (3 participants were not treated) and 101 
(14.1%) discontinued treatment and 614 (85.5%) participants completed the study. The 
proportion of participants who experienced all-causality TEAEs was similar across treatment 
groups up to Week 24 (placebo-controlled period) and up to Week 48 (overall). Up to Week 
24, the most frequently reported TEAEs in any group included nasopharyngitis, headache, 
and upper respiratory tract infection. The incidence of nasopharyngitis, folliculitis, urticaria, 
dizziness and urinary tract infection was higher in participants treated with ritlecitinib 
(particularly 200/50 mg and 200/30 mg) than placebo. Most TEAEs were mild to moderate in 
severity. Fourteen participants experienced 16 SAEs up to Week 48: 

200/50 mg (4 participants): appendicitis; empyema and sepsis; invasive lobular breast 
carcinoma, spontaneous abortion. 

200/30 mg (2 participants): appendicitis; chemical poisoning and suicidal behavior. 

50 mg (2 participants): breast cancer; pulmonary embolism.

30 mg (1 participant): diverticulitis. 

10 mg (2 participants): suicidal behavior; eczema.

Placebo-200/50 mg: no SAEs. 

Placebo-50 mg (3 participants): spontaneous abortion; conversion disorder; heavy 
menstrual bleeding. These treatment-emergent SAEs were all reported during the 
Placebo-Controlled Period. 
Of the 16 SAEs, 12 were considered by the investigator as unrelated to study intervention. 
The 4 SAEs that were considered related to study intervention in the opinion of the 
investigator were sepsis and empyema (both in 1 participant); breast cancer; and eczema. 
There were no deaths in the study.


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Treatment with ritlecitinib was associated with changes in hematological parameters, some of 
which were dose dependent. In the first weeks of the study, there were slight, transient 
decreases in hemoglobin and small, variable changes in neutrophil and leukocyte levels. 
Small, early decreases in platelets were observed with ritlecitinib treatment; these levels 
remained stable up to Week 48. Dose-dependent early decreases in absolute lymphocyte 
levels, T lymphocytes (CD3) and T lymphocyte subsets (CD4 and CD8) were observed. 
There was a dose-dependent early decrease in CD16/56 (NK cells), particularly in groups 
who had received a 200 mg loading dose of Ritlecitinib for 4 weeks. Overall, there were no 
clinically meaningful effects of ritlecitinib on ALT, AST, bilirubin, or alkaline phosphatase. 
The incidence of elevation in hepatic enzymes was low and not dose dependent. Up to Week 
48, there were no potential Hy’s law cases. 
2.2.4.3.7. Phase 3 Study in Alopecia Areata
Study B7981032 is an ongoing 5-year Phase 3 open-label, multicenter study to evaluate the
safety and efficacy of ritlecitinib in adult and adolescent participants ≥12 years of age with 
AA. The study has 2 treatment periods and an observation period with a maximum duration 
of approximately 38 months in the TP1. This phase includes up to a 5-week screening period, 
a 36-month open-label treatment period, and a 4-week follow-up period when not 
participating in the TP2. The TP2 is available for participants in countries where ritlecitinib 
is not commercially available at the time of their Month 36 visit. This includes up to 24 
months of study intervention (or until availability of commercial product in their country, or 
until the sponsor terminates the study in that country, whichever occurs first) and a 4-week 
follow-up period after completion or discontinuation of the study intervention. Study 
B7981032 includes eligible participants enrolling from the index Studies B7931005 and 
B7981015, as well as de novo participants (ie, those who have not previously received study 
intervention in Study B7931005 or B7981015).
As of 30 May 2022, a total of 1050 participants were evaluable for AEs, of whom 832 had
reported 3369 TEAEs. The most frequently (≥5% of participants) reported TEAEs were 
SARS-CoV-2 test positive (17.8%), headache (14.3%), cough (7.9%), pyrexia (7.9%), and 
acne (7.7%). As of 30 May 2022, 56 (5.3%) participants were permanently discontinued 
from study intervention and/or the study due to a TEAE.
As of 30 May 2022, 45 participants had experienced 53 SAEs. There were 2 deaths reported 
in Study B7981032: a participant with breast cancer, and another with both acute respiratory 
failure and cardiorespiratory arrest.
2.3. Benefit/Risk Assessment
Ritlecitinib is not expected to provide any clinical benefit to healthy participants of this 
study.  This study is designed primarily to generate PK data for further ritlecitinib
development.  In this study, ritlecitinib will be administered at single doses of 30 mg.
Ritlecitinib was determined to be well tolerated and to have an acceptable safety profile in 
the clinical studies.


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Based on clinical data (single oral doses of ritlecitinib up to 800 mg and multiple oral doses 
up to 400 mg), both 400 mg QD and 200 mg BID have demonstrated their safety and 
tolerability in healthy participants.  The dose of 200 mg QD has demonstrated safety and 
tolerability of up to 8 weeks in RA patients (B7981006).  In those studies, no clinically 
significant changes in vital signs, electrocardiogram or laboratory data were observed.  No 
dose limiting AEs were reported and no participants met the protocol specified individual 
stopping rules. Additionally, 30 mg was one of the doses tested for up to 48 weeks in AA 
participants in the Phase 2b/3 Study (B7981015), and the 30 mg dose was demonstrated to be 
safe and well tolerated. Hence, ritlecitinib is predicted to be well tolerated at a dose of 30 mg 
in this study.
Ritlecitinib is an immunomodulator and, as such, can be associated with the potential risk of 
infections (including serious infections), opportunistic infections, and viral reactivation. The 
risk of infection will be monitored in this study. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ritlecitinib may be found in the IB, which is SRSD for this study. 


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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention ritlecitinib 

viral reactivation

serious infections and opportunistic 
infections

malignancy and lymphoproliferative 
disorders

thromboembolism

dermatologic effects (eg. rash, acne, 
folliculitis, urticaria)

reduction in platelet count and lymphocyte 
count
Clinical experience with other JAK inhibitors 
Ritlecitinib clinical studies (B7931005, 
B7981015, B7981019, B7981032, and 
B7981037) and pre-clinical studies
Exclusion of participants at risk. Short duration of 
treatment. Safety labs at screening and  baseline 
and when deemed necessary by the investigator 
throughout the study. AE monitoring throughout the 
study.
Study Procedures blood collection for PK
Extravasation, bruising, local discomfort
Collection of 12 PK plasma samples per period 
per sequence
Collection of 6 PK microsamples collected 
during Treatment A. 
Use of highly qualified nurses, with venipuncture 
experience. When possible, use of IV canula, 
allowing all samples per dose to be collected with 
just one venipuncture.
Use of alternating arms for adjacent time points 
can provide more resting and healing time for each 
arm between samplings. 
Use of a warming pad (a disposable warming pad 
is provided in the sampling kit) can promote blood 
circulation prior to sampling to reduce the 
potential risk of bleeding caused by rubbing the 
sampling site which contains the unhealed lancet 
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Tolerability and safety will be assessed for all treatments by monitoring adverse events.
Participants who withdraw from the study may be replaced at the discretion of the 
investigator upon consultation with the sponsor.
4.2. Scientific Rationale for Study Design
The intent of this study is to estimate the impact of administration methods on the 
bioavailability of pediatric ritlecitinib BiC. 
Applesauce, strawberry jam, full-fat yoghurt, and high fat meal were selected to represent 
different food types to enable extrapolation to other foods with the goal of minimizing the 
food types evaluated. 
4.2.1. Choice of Contraception/Barrier Requirements 
In animals, ritlecitinib was associated with fetal changes in bones and some internal organs, 
and lower fetal body weights.  It is not known whether ritlecitinib is secreted into human 
milk. Because of that and because of the investigational nature of ritlecitinib, it should not be 
administered to pregnant women, breastfeeding women, or fertile WOCBP who are 
unwilling or unable to use contraception as defined in the study protocol. Men in the study 
are not required to use birth control, because ritlecitinib is not likely to transfer to a partner 
through semen at pharmacologically relevant blood levels (see Appendix 4).
4.2.2. Collection of Retained Research Samples
Retained Research Samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
The current study will use ritlecitinib at a dose of 30 mg which is the lowest strength 
available for the reference adult capsules.  The 30 mg dose of ritlecitinib is considered a 
clinically relevant dose for the pediatric population. Additionally, the 30 mg dose is predicted 
to be well tolerated (see Section 2.3). 
4.4. End of Study Definition
A participant is considered to have completed the study if they have completed all phases of 
the study, including the last scheduled procedure shown in the SoA and the investigator has 
reviewed the final safety data and determined that no additional evaluation is required.
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.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. Use of a 
prescreening tool is utilized for study recruitment purposes, it will include collection of 


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information that reflects the enrollment of a diverse participant population including, where 
permitted under local regulations, age, sex, and race, and ethnicity. The following eligibility 
criteria are designed to select participants for whom participation in the study is considered 
appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular participant is suitable for this protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Participants aged 18 or older (or the minimal age of consent in accordance with 
local regulations) at screening.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and 
female (Section 10.4.2) participants.
2. Male and female participants who are healthy as determined by medical 
evaluation including a detailed medical history, full physical examination, which 
includes BP and pulse rate measurement, clinical laboratory tests, temperature, 
and 12-lead ECG.
Other Inclusion Criteria:
3. BMI of 16 to 32 kg/m2, and a total body weight >45 kg (99 lb).
4. Participants who are willing and able to comply with all scheduled visits, 
treatment plan, laboratory tests, lifestyle considerations, and other study 
procedures.
5. Capable of giving signed informed consent as described in Appendix 1
(Section 10.1.3), which includes compliance with the requirements and 
restrictions listed in the ICD and in this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).


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2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
3. Known immunodeficiency disorder, including positive serology for HIV, or a first 
degree relative with a hereditary immunodeficiency.
4. Infection with hepatitis B or hepatitis C viruses according to protocol specific testing 
algorithm.
5. a. For hepatitis B, all participants will undergo testing for HBsAg and HBcAb.

If HBsAg is positive, the participant must be excluded from participation in 
the study.

If HBsAg and HBcAb are both negative, the participant is eligible for study 
inclusion.

If HBsAg is negative and HBcAb is positive, HBsAb should be evaluated:
6. i. If HBsAb is negative, the participant must be excluded from participation 
in the study;
7. ii. If HBsAb is positive, the participant is eligible for study inclusion.
8. b. For hepatitis C, all participants will undergo testing for HCVAb. Only participants 
who are HCVAb negative are eligible.
9. Participants with any of the following acute or chronic infections or infection history:

Any infection requiring treatment within 2 weeks prior to dosing.

Any infection requiring hospitalization or parenteral antimicrobial therapy 
within 60 days of the first dose of study intervention.

Any infection judged to be an opportunistic infection or clinically significant 
by the investigator, within the past 6 months of the first dose of study 
intervention.

Known active or history of recurrent bacterial, viral, fungal, mycobacterial or 
other infections.

History of recurrent (more than one episode of) localized dermatomal herpes 
zoster, or history of disseminated (single episode) herpes simplex or 
disseminated herpes zoster.
10. History of febrile illness within 5 days prior to the first dose of study intervention.


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11. History of any lymphoproliferative disorder such as EBV related lymphoproliferative
disorder, history of lymphoma, history of leukemia, or signs or symptoms suggestive
of current lymphatic or lymphoid disease.
12. Known present or a history of malignancy other than a successfully treated or excised 
nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in 
situ.
13. Evidence of untreated or inadequately treated active or latent Mycobacterium TB 
infection as evidenced by the following:

A positive QFT-G test performed within the 12 weeks prior to screening. If 
the laboratory reports the test as indeterminate, the test should be repeated. If 
the result of the repeat test is indeterminate, a PPD test may be substituted for 
the QFT-G test only with approval from the Pfizer Medical Monitor on a case-
by-case basis.

History of either untreated or inadequately treated latent or active TB 
infection.
o
If a participant has previously received an adequate course of therapy 
for either latent (9 months of isoniazid in a locale where rates of 
primary multi-drug resistant TB infection are <5% or an acceptable 
alternative regimen) or active (acceptable multi-drug regimen) TB 
infection, neither a QFT-G test nor a PPD test need be obtained. 
Details of the previous course of therapy (eg, medication(s) used, dose, 
duration of therapy) should be documented in the source 
documentation.
o
A participant who is currently being treated for active or latent TB 
infection must be excluded from the study.
14. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior, laboratory abnormality or other conditions that may 
increase the risk of study participation or, in the investigator’s judgment, make the 
participant inappropriate for the study.
Prior/Concomitant Therapy:
15. 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 6.9 Prior and Concomitant Therapy for additional 
details).
16. Use of injectable hormone therapy (eg, DepoProvera®) within 6 months prior to the 
first dose of study intervention.


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17. Vaccination with live attenuated replication-competent vaccine within the 6 weeks 
prior to the first dose of study intervention. (Refer to Section 5.3.5 for additional 
details).
Prior/Concurrent Clinical Study Experience:
18. Previous administration of an investigational product (drug or vaccine) within 
30 days (or as determined by the local requirement) or 5 half-lives preceding the first 
dose of study intervention used in this study (whichever is longer).
Diagnostic Assessments:
19. A positive urine drug test.
20. A positive serum pregnancy test.
21. 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.
22. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening or Day -1, as assessed by the study-specific laboratory and confirmed by a 
single repeat test, if deemed necessary: 

AST or ALT level > 1.5 × ULN;

Total bilirubin level >1.5 × ULN; participants with a history of Gilbert’s 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is ≤ULN;

Hemoglobin level <120 g/L (12.0 g/dL);

Platelet count <150 × 109/L (150,000 cells/mm3);

ANC <1.2 × 109/L (1200 cells/mm3);

ALC <0.8 × 109/L (800 cells/mm3);

eGFR <75 mL/minute/1.73 m2 based on the CKD-EPI equation;

In the opinion of the investigator or Pfizer (or designee), have any clinically
significant laboratory abnormality that could affect interpretation of study data or 
the participant's participation in the study.


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Other Exclusion Criteria:
23. 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).
24. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing.
25. Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.
26. History of severe allergic or anaphylactic reactions.
27. WOCBP who are unwilling or unable to use an acceptable method of contraception as 
outlined in Section 10.4 during the intervention period and for at least 28 days after 
the last dose of study intervention.
28. Females on HRT and whose menopausal status is in doubt.
29. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol.
30. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members.
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Contraception
The investigator or their designee, in consultation with the participant, will confirm that the 
participant is utilizing an appropriate method of contraception for the individual participant
and their partner(s) from the permitted list of contraception methods (see Appendix 4,
Section 10.4.4) and will confirm that the participant has been instructed in its consistent and 
correct use. At time points indicated in SoA, the investigator or designee will inform the 
participant of the need to use acceptable effective contraception consistently and correctly 
and document the conversation and the participant’s affirmation in the participant’s chart. 
Participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception, considering that their risk for pregnancy may have changed since 
the last visit. 
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued and document the requirement to use an 


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alternate protocol-specified method, including if the participant will no longer use abstinence 
as the selected contraception method, or if pregnancy is known or suspected in the participant 
or partner.
5.3.2. Meals and Dietary Restrictions

Participants must abstain from all food and drink (except water) at least 4 hours prior 
to any subsequent safety laboratory evaluations and 10 hours prior to the collection of 
the predose PK sample.

For the fed period (Treatment E), a high-fat (approximately 50% of total caloric 
content of the meal), high-calorie (approximately 800 to 1000 calories) meal will be 
used for the evaluation of a food effect in this study. On Day 1 of the fed period 
(Treatment E) following an overnight fast of at least 10 hours, participants should 
begin breakfast approximately 30 minutes prior to Ritlecitinib administration. The 
breakfast will be consumed over approximately 20-minute interval with Ritlecitinib 
administered within approximately 10 minutes of completion of the meal. Participants 
must complete the entire breakfast. There are no water restrictions prior to and after 
dosing.

For the fasted periods, water is permitted until 1 hour prior to study intervention
administration. Water may be consumed without restriction beginning 1 hour after 
dosing. Non-caffeinated 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 hours after dosing.

Dinner will be provided approximately 9 to 10 hours after dosing.

In the fed periods, lunch and dinner will be provided at similar times to the fasting 
periods. 

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 study intervention 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.
5.3.3. 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.


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
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 and during 
confinement in 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.
5.3.4. Activity

Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests. Walking at a normal pace will be permitted;

In order to standardize the conditions on PK sampling days, participants will be 
required to refrain from lying down (except when required for BP, pulse rate, and 
ECG measurements), eating, and drinking beverages other than water during the first 
4 hours after dosing;
5.3.5. Vaccination
Vaccination with live attenuated replication-competent vaccines is prohibited within the 6 
weeks prior the first dose of study intervention, while receiving study intervention, and for 6 
weeks after the last dose of study intervention. Similarly, current routine household contact 
with individuals who have been vaccinated with live attenuated, replication-competent 
vaccines should be avoided while receiving study intervention and for 6 weeks after the last 
dose of study intervention. Following vaccination with a live attenuated 
replication-competent vaccine, the virus may be shed in bodily fluids, including stool, and 
there is a potential risk that the virus may be transmitted.
Such vaccines include, but are not limited to: FluMist® (intranasal influenza vaccine), 
attenuated rotavirus vaccine, varicella (chickenpox) vaccine, attenuated typhoid fever 
vaccine, oral polio vaccine, MMR vaccine, vaccinia (smallpox) vaccine, and Zostavax® 
(zoster vaccine live). 
Live attenuated vaccines that are known not to be replication-competent in humans are 
permitted. Such vaccines include but are not limited to the Modified Vaccinia Ankara 
Bavarian Nordic (Jynneos®, Imvamune®, Imvanex®) smallpox and monkeypox vaccine. By 
contrast, the ACAM2000 smallpox and monkeypox vaccine is prohibited because it is live 
and replicates in humans.
Vaccines (including COVID-19 vaccines) that are not live attenuated are permitted.
Individuals receiving immunosuppressive therapy may have a diminished response to
vaccination.


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5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. Screen failure data are collected and remain as 
source and are not reported on the CRF.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study interventions are all prespecified investigational and noninvestigational medicinal 
products/auxiliary medicinal products, medical devices, and other interventions (eg, surgical 
and behavioral) intended to be administered to the study participants during the study 
conduct.
For the purposes of this protocol, study intervention refers to ritlecitinib pediatric BiC at 30 
mg dose (1 x 30 mg).
6.1. Study Intervention(s) Administered
Study intervention will be administered orally and according to the conditions described in 
the SoA section and Meals and Dietary Restrictions section of this protocol.
Study Intervention(s)
Intervention Name
Ritlecitinib
Arm Name
(group of participants receiving a 
specific treatment or no 
treatment)
Active study medication (Treatments: A, B, C, D, E)
Type
Intervention type: drug
Dose Formulation
Capsule
Unit Dose Strength(s)
30 mg
Dosage level(s)
30 mg
Route of Administration
Oral
Use
Experimental
IMP or NIMP/AxMP
IMP
Sourcing
Ritlecitinib provided centrally by the sponsor.
Soft foods (Applesauce, Yoghurt, Strawberry Jam) provided locally by the trial 
site. 


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Study Intervention(s)
Packaging and Labeling
The ritlecitinib 30 mg capsule will be provided in bulk. Each individual dosing 
container will be prepared and labeled at the CRU as required per country 
requirement. 
Current/former Name(s)
or Alias(es)
Ritlecitinib
Ritlecitinib
Study Arm(s)
Arm Title
Period 1
Period 2
Period 3
Period 4
Period 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm 
Description
Participants will receive a single dose of IP on Day 1 of each period. Administration of IP 
will be via dosing using intact BiCs with water or by emptying the capsule contents on 
soft food as per dosing instructions in Section 4.1.
Capsules will be supplied to the CRU in bulk along with individual dosing containers for unit
dosing.
6.1.1. Administration
For fasted periods: 

Following an overnight fast of at least 10 hours, the participants will receive study 
intervention at approximately 08:00 hours (plus or minus 2 hours) without 
breakfast/standard meal on Day 1.
For fed period:

Following an overnight fast of at least 10 hours, participants will receive breakfast 
approximately 30 minutes prior to dosing which is to be completed within 
approximately 20 minutes as outlined in Section 5.3.2 (Meals and Dietary 
Restrictions). The participants will then receive study intervention at approximately 
08:00 hours (plus or minus 2 hours).

The participants will then receive study intervention at approximately 08:00 hours 
(plus or minus 2 hours). PF-06651600 should be administered within approximately 
10 minutes of completion of the meal.
For all periods:

Investigator site personnel will administer study intervention during each period with 
ambient temperature water to a total volume of approximately 240 mL. For 
treatments A and E only: Participants will swallow the study intervention whole, and 
will not manipulate or chew the study intervention prior to swallowing.  Administer 
study intervention according to the IP Manual. 


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
In order to standardize the conditions on PK sampling days, all participants will be 
required to refrain from lying down (except when required for BP, pulse rate, and 
ECG measurements), eating, and drinking beverages other than water during the first 
4 hours after dosing.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm that appropriate conditions (eg, 
temperature) have been maintained during transit for all study interventions received 
and any discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply, prepare, and/or administer study intervention.
3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated recording) area in accordance with the labeled 
storage conditions with access limited to the investigator and authorized site staff. At 
a minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented upon 
return to business.
4. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with actions taken. The site should actively 
pursue options for returning the study intervention to the labeled storage conditions, 
as soon as possible. Once an excursion is identified, the study intervention must be 
quarantined and not used until Pfizer provides permission to use the study 
intervention. Specific details regarding the excursion definition and information to
report for each excursion will be provided to the site in the IPM.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
6. Study interventions should be stored in their original containers.
7. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final 
disposition records), such as the IPAL or sponsor-approved equivalent. All study 
interventions will be accounted for using a study intervention accountability 
form/record.
8. Further guidance and information for the final disposition of unused study 
interventions are provided in PCRU’s site procedures. All destruction must be 
adequately documented. If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 


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applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
9. Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IPM.
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
participant, in accordance with this protocol. Local health authority regulations or 
investigator site guidelines may use alternative terms for these activities.
Capsules will be prepared at the CRU in the individual dosing containers by 2 operators, 1 of 
whom is an appropriately qualified and experienced member of the study staff (eg, physician, 
nurse, physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist). 
The capsules will be provided in unit dose containers and labeled in accordance with Pfizer 
regulations and the clinical site’s labeling requirements. 
See the IPM for instructions on how to prepare the study intervention for administration for
treatments with capsule contents sprinkled on soft foods. 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.
6.3. Assignment to Study Intervention
The investigator’s knowledge of the treatment must not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
The investigator will assign participant numbers to the participants as they are screened for 
the study. Pfizer will provide a randomization schedule to the investigator and, in accordance 
with the randomization numbers, the participant will receive the study treatment regimen 
assigned to the corresponding randomization number.
Study intervention will be dispensed at the study visits summarized in the SoA.
6.4. Blinding
As this is an open-label study, the sponsor may conduct unblinded reviews of the data during 
the course of the study for the purpose of safety assessment, facilitating dose-escalation 
decisions, facilitating PK/PD modeling, and/or supporting clinical development.
6.4.1. Blinding of Participants
Participants will be unblinded to their assigned study intervention.


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6.4.2. Blinding of Site Personnel
Investigators and other site staff will be unblinded to participants’ assigned study 
intervention. 
6.4.3. Blinding of the Sponsor
Sponsor staff will be unblinded to participants’ assigned study intervention. 
6.5. Study Intervention Compliance
When the individual dose for a participant is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second qualified member of the study site staff.
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention. For dosing using intact BiCs only (treatments A & E): Study site 
personnel will examine each participant’s mouth to ensure that the study intervention was 
ingested.
6.6. Dose Modification
Dose modification for ritlecitinib is not allowed. 
6.7. Continued Access to Study Intervention After the End of the Study
No study intervention will be provided to participants at the end of their study participation.
It is expected that participants will be treated as required with standard-of-care treatments, as 
advised by their usual care physician. 
6.8. Treatment of Overdose
For this study, any dose of ritlecitinib greater than 800 mg within a 24-hour time period will 
be considered an overdose.
There is no specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the study medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities as 
medically appropriate and at least until the next scheduled follow-up.
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.


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5. Obtain a blood sample for PK analysis within 4 days from the date of the last dose of 
study intervention if requested by the study medical monitor (determined on a 
case-by-case basis).
Decisions regarding dose interruptions will be made by the investigator in consultation with 
the study medical monitor as needed based on the clinical evaluation of the participant.
6.9. Prior and Concomitant Therapy
Participants will abstain from all concomitant treatments, except for the treatment of adverse 
events. 
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. Limited use of nonprescription medications that are not believed to affect 
participant safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor. Acetaminophen/paracetamol may be used at doses of 
≤3 g/day.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4). Use of injectable hormone therapy (eg, 
DepoProvera®) within 6 months prior to the first dose of study intervention is not permitted.
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration. All participants will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention 
will be documented as concomitant treatments.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: treatment-related 
SAEs, serious infections, and other events as described in Section 5.2. 
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant should remain in the study 
to be evaluated for safety. See the SoA for data to be collected at the time of discontinuation 
of study intervention and follow-up for any further evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 


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receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information.
7.1.1. Liver Injury 
A participant who meets the criteria as described in Appendix 6 will be withdrawn from 
study intervention. 
7.1.2. Potential Cases of Acute Kidney Injury
Abnormal values in SCr concurrent with presence or absence of increase in BUN that meet 
the criteria below, in the absence of other causes of kidney injury, are considered potential 
cases of acute kidney injury and should be considered important medical events. 
An increase of ≥0.3 mg/dL (or ≥26.5 µmol/L) in SCr level relative to the participant’s own 
baseline measurement should trigger another assessment of SCr as soon as practically 
feasible, preferably within 48 hours from awareness.
If the second assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 µmol/L] in SCr
relative to the participant’s own baseline measurement) is ≥0.4 mg/dL (or ≥35.4 µmol/L), the 
participant should be discontinued from the study and adequate, immediate, supportive 
measures taken to correct apparent acute kidney injury.
Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
SCr result. This evaluation should include laboratory tests, detailed history, and physical 
assessment. In addition to repeating SCr, laboratory tests should include serum BUN, serum 
creatine kinase, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
examination, and urinary indices. All cases confirmed on repeat testing as meeting the 
laboratory criteria for acute kidney injury, with no other cause(s) of laboratory abnormalities 
identified, should be considered potential cases of drug-induced kidney injury irrespective of 
availability of all the results of the investigations performed to determine etiology of the 
abnormal SCr. If ≥2 healthy participants in a given period are noted to have 2 consecutive
SCr results of ≥0.3 mg/dL (or ≥26.5 µmol/L), an assessment of whether the finding may be 
considered an adverse drug reaction should be undertaken.
7.1.3. Pregnancy 
Pregnancy tests are conducted as per SoA and dosing of study intervention will occur only in 
the presence of a negative pregnancy test. If a participant is confirmed to be pregnant (see 
Section 8.3.6) during any visit, further dosing with study intervention will be discontinued 
immediately and permanently. 
Section 8.4.5.1 Exposure During Pregnancy describes the follow-up activities if a participant 
meets the EDP criteria. 


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7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;

Adverse event.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal.
The participant will be permanently discontinued from the study intervention and the study at 
that time.
If a participant withdraws from the study, they may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations will be performed and no 
additional data will be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with them or persons previously authorized by the participant to provide this information. 
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate CRF page. In the event that vital status (whether 
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.


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7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1
(Section 10.1).
8. STUDY ASSESSMENTS AND PROCEDURES
8.1. Administrative Procedures
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention
to confirm that they meet the study population criteria for the study. If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.


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A participant who qualified for this protocol but did not enroll from an earlier cohort/group
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study. In 
addition, other clinical assessments or specimen collections, eg, retained research samples, 
may be used without repeat collection, as appropriate.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that make it unfeasible to perform the 
test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that they have taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
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 
170 mL (PK sample volume calculated as approximately 120 mL). The actual collection 
times of blood sampling may change. Additional blood samples may be taken for safety 
assessments at times specified by Pfizer, provided the total volume taken during the study 
does not exceed 550 mL during any period of 60 consecutive days.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Prior and Concomitant Therapy sections of the protocol.
8.1.1. Baseline Procedures 
All procedures listed in the SoA must be conducted at this visit. 
SoA must be conducted must be conducted at the screening visit. 
8.2. Efficacy Assessments
Not Applicable.
8.3. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety
measurements may be obtained at any time during the study to assess any perceived safety 
issues.
8.3.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 


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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 
Sections 8.4.1 to 8.4.3.
8.3.2. Vital Signs
8.3.2.1. Blood Pressure and Pulse Rate
Supine BP will be measured with the participant’s arm supported at the level of the heart, and
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study. Participants should be 
instructed not to speak during measurements.
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds. When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 3) must be reported according to the 
processes in Sections 8.4.1 to 8.4.3.
8.3.2.2. Temperature
Temperature will be measured orally. No eating, drinking, or smoking is allowed for 
15 minutes prior to the measurement.
8.3.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 


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automatically calculates the HR and measures PR interval, QT interval, QTcF, 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 
post-dose QTcF interval is increased by ≥60 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG. If either of these conditions occurs, 
then 2 additional ECGs will be collected approximately 2 to 4 minutes apart to confirm the 
original measurement. If the QTcF values from these repeated ECGs remain above the 
threshold value, then a single ECG must be repeated at least hourly until QTc values from 
2 successive ECGs fall below the threshold value that triggered the repeat measurement.
If a) a postdose QTcF interval remains ≥60 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG for greater than 4 hours (or sooner, at 
the discretion of the investigator); or c) QTcF value get progressively longer, the participant
should undergo continuous ECG monitoring. A cardiologist should be consulted if QTcF
values do not return to less than the criteria listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 8.
8.3.4. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.  
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition.
All laboratory tests with values considered clinically significant and abnormal during 
participation in the study or within 28 days after the last dose of study intervention should be 


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repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or study medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
DILI.
See Appendix 7 for instructions for laboratory testing to monitor kidney function and 
reporting laboratory test abnormalities.
Participants may undergo random urine drug testing at the discretion of the investigator.
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.3.5. COVID-19 Specific Assessments
Participants will be tested for 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.
8.3.6. Pregnancy Testing 
A serum pregnancy test is required at screening. Following screening, pregnancy tests may 
be urine or serum tests, and must have a sensitivity of at least 25 mIU/mL. Pregnancy tests 
will be performed in WOCBP at the times listed in the SoA. Following a negative pregnancy 
test result at screening, appropriate contraception must be commenced, and a second negative 
pregnancy test result will be required at the baseline visit prior 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). Pregnancy tests may also be repeated if requested by IRBs/ECs or if required by 
local regulations.
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the
participant (or, when appropriate, by a caregiver, surrogate, or the participant’s legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 


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event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.4.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.4.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before undergoing any study-related procedure and/or receiving study 
intervention), through and including a minimum of 28 calendar days, except as indicated 
below, after the last administration of the study intervention.
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator.
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and they consider 
the event to be reasonably related to the study intervention, the investigator must promptly 
report the SAE to Pfizer using the CT SAE Report Form.
8.4.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.4.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of its being available.


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8.4.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.4.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.4.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.4.3. Follow-Up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is provided in Appendix 3.
8.4.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.


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Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure.
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.4.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of environmental exposure. Below are 
examples of environmental EDP:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, or skin contact.
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, the investigator must report this information to Pfizer 
Safety on the CT SAE Report Form and an EDP Supplemental Form, regardless of 
whether an SAE has occurred. Details of the pregnancy will be collected after the 
start of study intervention and until 28 days after the last dose.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.


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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 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion should be reported 
as an SAE;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.5.2. Exposure During Breastfeeding
An EDB occurs if: 

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

A female nonparticipant is found to be breastfeeding while being exposed or having 
been exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports 
that she is breastfeeding after having been exposed to the study intervention by 
ingestion, inhalation, or skin contact.


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The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the CT SAE Report Form. When EDB occurs in the setting of environmental exposure, 
the exposure information does not pertain to the participant enrolled in the study, so the 
information is not recorded on a CRF. However, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
An EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB.
8.4.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 24 
hours of the investigator’s awareness using the CT SAE Report Form regardless of whether 
there is an associated SAE. Since the information about the occupational exposure does not 
pertain to a participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed CT SAE Report Form must be maintained in the 
investigator site file.
8.4.6. Cardiovascular and Death Events
Not applicable
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable
8.4.8. Adverse Events of Special Interest
Not applicable
8.4.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.4.9. Medical Device Deficiencies
Not applicable
8.4.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.


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Medication errors are recorded and reported as follows:
Recorded on the 
Medication Error Page 
of the CRF
Recorded on the 
Adverse Event Page 
of the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
All (regardless of whether 
associated with an AE)
Any AE or SAE associated 
with the medication error
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.5. Pharmacokinetics 
Blood samples of approximately 2 mL, to provide a minimum of 0.5 mL of plasma, will be 
collected for measurement of plasma concentrations of ritlecitinib as specified in the SoA. 
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor. The actual date and time (24-hour clock time) of each 
sample will be recorded.
The actual times may change, but the number of samples will remain the same.  All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing.  Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time (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, CRF/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, CRF/DCT). 


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Samples will be used to evaluate the PK of ritlecitinib.  Samples collected for analyses of 
ritlecitinib concentration may also be used to evaluate safety or efficacy aspects related to 
concerns arising during or after the study, or for other internal exploratory purposes.
Genetic analyses will not be performed on these plasma samples.  Participant confidentiality 
will be maintained.
Samples collected for measurement of plasma concentrations of ritlecitinib  will be analyzed 
using a validated analytical method in compliance with applicable SOPs.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor.  
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment.  The IRB will be 
informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
Additional blood samples of approximately 0.5-1 mL using a micro sampling device (Tasso) 
will be collected, to provide approximately 0.25-0.5 mL serum into appropriately labeled 
tubes for measurement of ritlecitinib at selected timepoints as specified in the SoA Table.
The “Tasso device” is a patient-centric sterile, disposable, integrated capillary blood 
collection device, including an at-home lancet assembly and a detachable reservoir, for the 
collection of blood by the user or caregiver in-home settings, without the need of a highly 
trained phlebotomist. This part of the study is designed to validate ritlecitinib PK 
concentrations in capillary blood collected using the Tasso device against PK samples 
collected from traditional venous blood samples. Findings from the validation may enable 
patient-centric blood sampling using this innovative device in future ritlecitinib clinical 
studies. 
Blood samples from capillary blood vessels, collected using the Tasso device, should be 
timed as close as possible to the collection of ritlecitinib blood samples. The Tasso device 
should be attached to the upper arm. Details for collection and handling of the samples will 
be provided in the laboratory manual. 
The blood samples collected using Tasso device will be used for internal exploratory 
purposes for comparing the ritlecitinib concentrations between venous and capillary blood. 
The results from this comparison will be documented in a separate internal bioanalytical 
report and will not be included in the CSR.




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9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
No statistical hypothesis will be tested in this study. 
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Population
Description
PK Concentration
The PK concentration population is defined as all participants 
randomized and treated who have at least 1 concentration in at 
least 1 treatment period.
PK Parameter
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.
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. Efficacy Analyses
An efficacy analysis is not applicable to this study. 
9.3.2. Safety Analyses
AEs 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.
CCI


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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.
9.3.3. Pharmacokinetic Analyses
PK parameters following a single dose administration will be derived from the 
concentration-time profiles using noncompartmental methods as data permit. The various 
PK parameters to be assessed in this study, their definition, and method of determination are 
outlined in Table 4. In all cases, actual PK sampling times will be used in the derivation of 
PK parameters.
Table 4.
Definitions of PK Parameters
Parameter
Definition
Method of Determination
AUClast
Area under the plasma concentration-time 
profile from time zero to the time of the last 
quantifiable concentration (Clast)
Linear-log trapezoidal method
AUCinf
Area under the plasma concentration-time 
profile from time zero extrapolated to 
infinite time
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 the data
Tmax
Time for Cmax
Observed directly from the data as time of first 
occurrence
t1/2
Terminal elimination half-life
Loge(2)/kel
Only those data points judged to describe the 
terminal log-linear decline will be used in the 
regression.
CL/F
Apparent clearance after oral dose
Dose/AUCinf after oral dose
Vz/F
Apparent volume of distribution after oral 
dose
Dose/(AUCinf*kel) after oral dose
The plasma PK parameters in Table 4 will be summarized descriptively by treatment, as
applicable, in accordance with Pfizer data standards. Plasma concentrations will be listed and 
summarized descriptively by 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.




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table presents the widths of 90% confidence interval for different estimated effects for 12 
participants:
Parameter
Estimated Effect
(100*Test/Reference)
90%CI
CI Width
AUCinf
85%
77.75% to 92.92%
  15.17%
90%
82.33% to 98.39%
             16.06%
95%
86.9% to 103.85%
             16.95%
100%
91.47% to 109.32%
17.85%
105%
96.05% to 114.79%
18.74%
110%
100.62% to 120.25%
19.63%
115%
105.20% to 125.72%
20.52%
Cmax
85%
71.56% to 100.97%
29.41%
90%
75.77% to 106.91%
31.14%
95%
     79.98% to 112.84%
32.87%
100%
     84.19% to 118.78%
34.60%
105%
88.40% to 124.72%
36.33%
110%
92.60% to 130.66%
38.06%
115%
     96.81% to 136.60%
39.79%
These calculations are based on the estimates of within-participant standard deviations of 
0.117 and 0.226 for loge AUCinf and logeCmax, respectively, as obtained from studies 
B7981022, B7981029, and B7981030. 
Participants who withdraw from the study or whose PK samples are determined to be 
non-analyzable may be replaced at the discretion of the investigator upon consultation with
the sponsor.


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


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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participant or their legally authorized representative 
and answer all questions regarding the study. The participant or their legally authorized 
representative 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 or their 
legally authorized representative (if allowed by local regulations) will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, privacy and data protection requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each participant or their legally authorized representative 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 or their legally authorized representative must be informed that their personal 
study-related data will be used by the sponsor in accordance with local data protection law. 
The level of disclosure must also be explained to the participant or their legally authorized 
representative.
The participant or their legally authorized representative must be informed that their medical
records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities.
The investigator further must ensure that each study participant or their legally authorized 
representative is fully informed about their right to access and correct their personal data and 
to withdraw consent for the processing of their personal data.


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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 or their legally authorized representative must be reconsented to the most current 
version of the IRB/EC-approved ICD(s) during their participation in the study as required per 
local regulations.
A copy of the ICD(s) must be provided to the participant or their legally authorized 
representative (if allowed by local regulations).
Participants who are rescreened are required to sign a new ICD.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to their actual identity and medical record ID. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access.
The sponsor maintains standard operating procedures on how to respond in the event of 
unauthorized access, use, or disclosure of sponsor information or systems.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee
This study will not use an E-DMC. 


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10.1.6. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT/CTIS, and/or 
www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable
information anonymized.
Documents within marketing applications
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
Data sharing
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized.


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Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.7. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties.
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the CSR.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study-critical data items and 
processes (eg, risk-based initiatives in operations and quality, such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring 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.
10.1.8. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
In this study, the CRF 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 CRF and for which 
the CRF will be the source document.
Definition of what constitutes source data and its origin can be found in the Source 
Document Locator, which is maintained by the Pfizer CRU.
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the Pfizer CRU.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The sponsor or designee will perform monitoring to confirm that data entered into the CRF 
by authorized site personnel are accurate, complete, and verifiable from source documents; 
that the safety and rights of participants are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.9. 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.


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The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. Study sites will be closed upon study completion. A study site is considered 
closed when all required documents and study supplies have been collected and a study-site 
closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the CRO if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor’s procedures, or the ICH GCP 
guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.10. Publication Policy
For multicenter trials, the primary publication will be a joint publication developed by the 
investigator and Pfizer reporting the primary endpoint(s) of the study covering all study sites. 
The investigator agrees to refer to the primary publication in any subsequent publications. 
Pfizer will not provide any financial compensation for the investigator’s participation in the 
preparation of the primary congress abstract, poster, presentation, or primary manuscript for 
the study.
Investigators are free to publish individual center results that they deem to be clinically 
meaningful after publication of the overall results of the study or 12 months after primary 
completion date or study completion at all sites, whichever occurs first, subject to the other 
requirements described in this section.


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The investigator will provide Pfizer an opportunity to review any proposed publication or 
any other type of disclosure of the study results (collectively, “publication”) before it is 
submitted or otherwise disclosed and will submit all publications to Pfizer 30 days before 
submission. If any patent action is required to protect intellectual property rights, the 
investigator agrees to delay the disclosure for a period not to exceed an additional 60 days 
upon request from Pfizer. This allows Pfizer to protect proprietary information and to provide 
comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study intervention or Pfizer-related 
information necessary for the appropriate scientific presentation or understanding of the 
study results.  For joint publications, should there be disagreement regarding interpretation 
and/or presentation of specific analysis results, resolution of, and responsibility for, such 
disagreements will be the collective responsibility of all authors of the publication.
For all publications relating to the study, the investigator and Pfizer will comply with 
recognized ethical standards concerning publications and authorship, including those 
established by the International Committee of Medical Journal Editors. The investigator will 
disclose any relationship with Pfizer and any relevant potential conflicts of interest, including 
any financial or personal relationship with Pfizer, in any publications. All authors will have 
access to the relevant statistical tables, figures, and reports (in their original format) required 
to develop the publication.
10.1.11. Sponsor’s Medically Qualified Individual
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the CTMS.
To facilitate access to their investigator and the sponsor’s MQI for study-related medical 
questions or problems from non-study healthcare professionals, participants are provided 
with an ECC at the time of informed consent. The ECC contains, at a minimum, (a) protocol 
and study intervention identifiers, (b) participant’s study identification number, (c) site 
emergency phone number active 24 hours/day, 7 days per week.
The ECC is intended to augment, not replace, the established communication pathways 
between the participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. 


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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety issues.
Table 5.
Protocol Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
eGFR (CKD-EPI [serum 
Creatinine based])
Local dipstick:
pHa
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Laboratory:
Microscopyb
Urine drug 
screeningc
Pregnancy test (ꞵ-
hCG)d
At Screening Only
FSHe
HBsAgf
HBcAbf
HCVAbf
HIV
QuantiFERON- TB 
Gold Testg
a.
Can be performed on dipstick or pH-meter device.
b.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
c.
At Screening and Admission.  The minimum requirement for drug screening includes cocaine, THC, 
opiates/opioids, benzodiazepines, and amphetamines (others are site and study specific).
d.
Serum -hCG for female participants of childbearing potential.
e.
At Screening for confirmation of postmenopausal status only.
f.
If HBsAg is negative and HBcAb is positive, HBsAb should be evaluated.
g.
Complete at screening.  Previous testing for QuantiFERON TB Gold Test will be accepted if completed 
within 12 weeks prior to screening.  Otherwise the testing should be completed at screening and results 
available prior to Day 1.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.






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d. Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Is a suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic 
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.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are 
considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel.  Such cases are also 
considered for reporting as product defects, if appropriate.












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10.4. Appendix 4: Contraceptive and Barrier Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are not required to use contraception in this study, because ritlecitinib is 
not likely to transfer to a partner through semen at pharmacologically relevant blood levels.
10.4.2. Female Participant Reproductive Inclusion Criteria
The criteria below are part of Inclusion Criterion 1 (Age and Sex; Section 5.1) and specify 
the reproductive requirements for including female participants.  Refer to Section 10.4.4 for a 
complete list of contraceptive methods permitted in the study. 
A female participant is eligible to participate if she 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 agrees to use an acceptable contraceptive method during the 
intervention period (for a minimum of 28 days after the last dose of study 
intervention).  The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
10.4.3. Woman of Childbearing Potential.
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.


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For individuals with permanent infertility due to a medical cause other than the above
(eg, mullerian agenesis, androgen insensitivity), investigator discretion should be applied 
to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
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 highly effective nonestrogen hormonal contraception 
methods if she wishes to continue her HRT during the study. Otherwise, she
must discontinue HRT to allow confirmation of postmenopausal status before 
study enrollment.
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.
The following contraceptive methods are appropriate for this study:
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion or bilateral tubal ligation.
5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the WOCBP and the absence of sperm 
has been confirmed.  If not, an additional highly effective method of 


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contraception should be used.  The spermatogenesis cycle is approximately 90 
days.
Highly Effective Methods That Are User Dependent
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation used in combination with a barrier method:

Oral + barrier*

Intravaginal + barrier*

Transdermal + barrier*
7. Progestogen-only hormone contraception associated with inhibition of ovulation used 
in combination with a barrier method:

Oral + barrier*

Injectable + barrier*
Sexual Abstinence
8. 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.
* Acceptable barrier methods to be used concomitantly with options 6 or 7 for the study 
include any of the following

Male or female condom, with or without spermicide.

Cervical cap, diaphragm, or sponge with spermicide.
Male condom and female condoms should not be used together (due to risk of failure with 
friction).


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10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis.

The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or 
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.

The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to ritlecitinib (PF-06651600) or study interventions of this 
class to understand treatments for the disease(s) under study or the disease(s) 
themselves.

The results of genetic analyses may be reported in the CSR or in a separate study 
summary, or may be used for internal decision making without being included in a 
study report.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained as indicated:

Retained samples will be stored indefinitely or for another period as per local 
requirements.  

Participants may withdraw their consent for the storage and/or use of their Retained 
Research Samples at any time by making a request to the investigator; in this case, any 
remaining material will be destroyed. Data already generated from the samples will be 
retained to protect the integrity of existing analyses.  

Samples for genetic research will be labeled with a code. The key between the code 
and the participant’s personally identifying information (eg, name, address) will be 
held securely at the study site.


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


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The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and T bili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
T bili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.


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10.7. Appendix 7: Kidney Safety: Monitoring Guidelines
10.7.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury
Standard kidney safety monitoring requires assessment of baseline and postbaseline serum 
creatinine (SCr measurement to estimate glomerular filtration rate [SCr-based eGFR] or 
creatinine clearance [eCrCl]). Baseline and postbaseline serum Scys makes it feasible to 
distinguish AKI from other causes of SCr increase. If SCr increase is confirmed after 
baseline, then reflex measurement of Scys is indicated to estimate the combined SCr -Scys 
eGFR calculation (for adults only).
Regardless of whether kidney function monitoring tests are required as a routine safety 
monitoring procedure in the study, if the investigator or sponsor deems it necessary to further 
assess kidney safety and quantify kidney function, then these test results should be managed 
and followed per standard of care.
10.7.2. Age-Specific Kidney Function Calculation Recommendations
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations
2021 CKD-
EPI          
SCr Only
SCr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤ 0.7
N/A
eGFR = 143 × (SCr/0.7)-0.241  ×  (0.9938)Age
Female
if > 0.7
N/A
eGFR = 143 × (SCr/0.7)-1.200  ×  (0.9938)Age
Male
if ≤ 0.9
N/A
eGFR = 142 × (SCr/0.9)-0.302  ×  (0.9938)Age
Male
if > 0.9
N/A
eGFR = 142 × (SCr/0.9)-1.200  ×  (0.9938)Age
2021 CKD-
EPI          
SCr-Scys 
Combined
SCr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤ 0.7
if ≤ 0.8
eGFR = 130 × (SCr/0.7)-0.219  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if ≤ 0.7
if > 0.8
eGFR = 130 × (SCr/0.7)-0.219  × (Scys/0.8)-0.778  × (0.9961)Age
Female
if > 0.7
if ≤ 0.8
eGFR = 130 × (SCr/0.7)-0.544  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if > 0.7
if > 0.8
eGFR = 130 × (SCr/0.7)-0.544  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if ≤ 0.9
if ≤ 0.8
eGFR = 135 × (SCr/0.9)-0.144  × (Scys/0.8)-0.323  × (0.9961)Age
Male
if ≤ 0.9
if > 0.8
eGFR = 135 × (SCr/0.9)-0.144  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if > 0.9
if ≤ 0.8
eGFR = 135 × (SCr/0.9)-0.544  ×  (Scys/0.8)-0.323  × (0.9961)Age
Male
if > 0.9
if > 0.8
eGFR = 135 × (SCr/0.9)-0.544  ×  (Scys/0.8)-0.778  × (0.9961)Age
Inker LA et al. N Engl J Med. 2021;385:1737-49.1
10.7.3. Adverse Event Grading for Kidney Safety Laboratory Abnormalities
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to KDIGO
criteria. 






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10.10. Appendix 10: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AA
alopecia areata
Abs
absolute
ADL
activity/activities of daily living
AE
adverse event
AKI
acute kidney injury
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
ATE
arterial thromboembolism
AUC
area under the curve
AUCinf
area under the plasma concentration-time profile from time 0 
extrapolated to infinite time
AUClast
area under the plasma concentration-time profile from time 0 to the 
time of the last quantifiable concentration
AV
atrioventricular
AxMP
auxiliary medicinal product
BA
bioavailability
BAEP
brainstem auditory evoked potential
-hCG
-human chorionic gonadotropin
BiC
Blend-in capsule
BID
twice a day
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BUN
blood urea nitrogen
CD
Crohn’s Disease
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
CL/F
Apparent clearance after oral dose
Cmax
maximum observed concentration
CNS
central nervous system
CO2
carbon dioxide (bicarbonate)
COVID-19
coronavirus disease 2019


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Abbreviation
Term
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
Clinical Study Report
CT
clinical trial
CTMS
clinical trial management system
CTIS
Clinical Trial Information System
DCT
data collection tool
DILI
drug-induced liver injury
EBV
Epstein Barr Virus
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram or electrocardiography
eCrCl
estimated creatinine clearance
eCRF
electronic case report form
EDB
exposure during breastfeeding
E-DMC
External Data Monitoring Committee
EDP
exposure during pregnancy
EOT
End of treatment
EOI
event of interest
eGFR
estimated glomerular filtration rate
eSAE
electronic serious adverse event
EU
European Union
EudraCT
European Union Drug Regulating Authorities Clinical Trials 
(European Clinical Trials Database)
FSH
follicle stimulating hormone
F/U
follow-up
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg 
hepatitis B surface antigen
HCVAb
hepatitis C antibody
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
HZ
herpes zoster
IB
Investigator’s Brochure
ICD
informed consent document


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Abbreviation
Term
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
ID
identification
IL
interleukin
IMI
Innovative Medicines Initiative
IMP
investigational medicinal product
IND
Investigational New Drug 
INR
international normalized ratio
IP
investigational product
IPAL
Investigational Product Accountability Log
IPM
investigational product manual
IRB
Institutional Review Board
JAK
Janus kinase
KDIGO
Kidney Disease Improving Global Outcomes
kel
first-order elimination rate constant
t½
terminal phase half-life
LBBB
left bundle branch block
LFT
liver function test
MACE
Major Adverse Cardiac Events
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MMR
measles, mumps, rubella
MQI
medically qualified individual
MTX-IR
inadequate response to MTX
NA
not applicable
NIMP
non-investigational medicinal product
NMSC
non-melanoma skin carcinoma
NOAEL
no-observed-adverse-effect level
PCRU
Pfizer Clinical Research Unit
PK
pharmacokinetic(s)
PNS
peripheral nervous system
PPD
purified protein derivative
PSSA
Pfizer's Serious Adverse Event Submission Assistant
PT
prothrombin time
PVC
premature ventricular contraction/complex
QD
Once a day
QFT-G
QuantiFERON®-TB Gold In-Tube
QTc
corrected QT interval
QTcF
QTc corrected using Fridericia’s formula


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Abbreviation
Term
QTL
quality tolerance limit
qual
qualitative
RA
rheumatoid arthritis
RBC
red blood cell
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SCr
serum creatinine
Scys
serum cystatin C
SoA
schedule of activities
SOC
system organ class
SOP
standard operating procedure
SRSD
Single Reference Safety Document
SUSAR
Suspected Unexpected Serious Adverse Reaction
TB
tuberculosis 
T bili
total bilirubin
TEAE
treatment-emergent adverse events
TEC
tyrosine kinase expressed in hepatocellular carcinoma
THC
tetrahydrocannabinol
Tmax
time for maximum plasma concentration
TYK
tyrosine kinase
ULN
upper limit of normal
UC
ulcerative colitis
US
United States
WBC
white blood cell
WOCBP
woman/women of childbearing potential


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11. REFERENCES
1.
Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C-Based 
Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-49.

SAP_001.pdf: 
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Protocol B7981078
A Phase 1, Randomized, Open label, Crossover Study to Estimate the Relative 
Bioavailability of Pediatric Ritlecitinib Sprinkled in Applesauce, Yoghurt and Strawberry 
Jam Relative to Intact Blend-In Capsule of Ritlecitinib and the Effect of Food on the 
Bioavailability of the Capsule Dosage Formulation of Ritlecitinib in Healthy Adult 
Participants
Statistical Analysis Plan 
(SAP)
Version:
1
Date:
27 Mar 2023


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Modifications to the Analysis Plan Described in the Protocol..................................5
2.2. Study Objectives and Endpoints ...............................................................................5
2.3. Study Design .............................................................................................................6
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................7
3.1. Primary Endpoints.....................................................................................................7
3.2. Secondary Endpoints.................................................................................................8
3.3. Baseline Variables.....................................................................................................8
3.4. Other Endpoints.........................................................................................................8
3.4.1. Other PK parameters for ritlecitinib .............................................................8
3.4.2. Ritlecitinib microsampling concentration.....................................................8
3.4.3. Palatability of sprinkled ritlecitinib BiC.......................................................8
3.5. Safety Endpoints .......................................................................................................9
3.5.1. Adverse Events.............................................................................................9
3.5.2. Laboratory Data............................................................................................9
3.5.3. Vital Signs ....................................................................................................9
3.5.4. Electrocardiograms.......................................................................................9
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................10
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................10
5.1. Hypotheses and Decision Rules ..............................................................................10
5.2. General Methods .....................................................................................................10
5.2.1. Analyses for Binary/Categorical Endpoints ...............................................10
5.2.2. Analyses for Continuous Endpoints ...........................................................10
5.3. Methods to Manage Missing Data ..........................................................................11
5.3.1. Pharmacokinetic Data.................................................................................11
5.3.2. Safety Data..................................................................................................12
6. ANALYSES AND SUMMARIES ......................................................................................12


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6.1. Primary Endpoints...................................................................................................12
6.2. Secondary Endpoints...............................................................................................13
6.3. Other Endpoints.......................................................................................................13
6.3.1. Other PK parameters for ritlecitinib ...........................................................13
6.3.2. Ritlecitinib microsampling concentration...................................................14
6.3.3. Palatability of sprinkled ritlecitinib BiC.....................................................14
6.4. Subset Analyses.......................................................................................................14
6.5. Baseline and Other Summaries and Analyses.........................................................14
6.5.1. Demographic Summaries............................................................................14
6.5.2. Study Conduct and Participant Disposition................................................15
6.5.3. Study Treatment Exposure .........................................................................15
6.5.4. Concomitant Medications and Nondrug Treatments..................................15
6.6. Safety Summaries and Analyses .............................................................................15
6.6.1. Adverse Events...........................................................................................15
6.6.2. Laboratory Data..........................................................................................15
6.6.3. Vital Signs ..................................................................................................15
6.6.4. Electrocardiograms.....................................................................................15
7. INTERIM ANALYSES.......................................................................................................15
APPENDICES .........................................................................................................................16


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LIST OF TABLES
Table 1.
Summary of Changes..................................................................................5
Table 2.
Study Design and Treatments.....................................................................6
Table 3.
Definitions of PK Parameters.....................................................................8
Table 4.
PK Parameters to be Summarized Descriptively by Treatment ...............13
APPENDICES
Appendix 1. SAS Code for Analyses.......................................................................................16
Appendix 2. List of Abbreviations...........................................................................................17


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NOTE: Italicized text within this document has been taken verbatim from the Protocol.
1. VERSION HISTORY
Table 1.
Summary of Changes
Version/
Date
Associated Protocol 
Amendment
Rationale
Specific Changes
1 /
27 Mar 2023
Original 
02 Feb 2023
N/A
N/A
2. INTRODUCTION
Ritlecitinib is a covalent and irreversible inhibitor of JAK3 with high selectivity over the 
other JAK isoforms (JAK1, JAK2, and TYK2).  Ritlecitinib also inhibits irreversibly the TEC 
family kinases with selectivity over the broader human kinome.  Treatment with ritlecitinib is 
expected to inhibit the inflammatory pathways mediated by IL 7, IL 15 and IL 21, all 
implicated in UC, CD, AA, RA, and vitiligo.  Moreover, due to lack of activity against the 
other JAK isoforms, ritlecitinib is expected to spare immunoregulatory cytokines such as IL 
10, IL 27 and IL 35, which are critical to the maintenance of immunosuppressive functions 
and immune homeostasis.
The objective of this study is to estimate the impact of administration methods on the 
bioavailability of the pediatric ritlecitinib blend-in capsule (BiC) formulation.
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in Study B7981078.
2.1. Modifications to the Analysis Plan Described in the Protocol
None.
2.2. Study Objectives and Endpoints
Objectives
Endpoints
Primary: 
Primary: 

To estimate the relative BA of ritlecitinib 
pediatric capsules (BiC) when sprinkled on 
food (apple sauce, strawberry jam, and 
yoghurt) compared to intact blend-in capsules 
(reference) at a 30 mg dose under fasted 
conditions in adult healthy participants.

To estimate the effect of food on the relative BA 
of ritlecitinib pediatric capsules at a 30 mg 
dose.

Plasma AUCinf  and Cmax of ritlecitinib.




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Table 2.
Study Design and Treatments
Treatment D: contents of ritlecitinib 1 x 30 mg pediatric capsule sprinkled on applesauce in fasted state
Treatment E: ritlecitinib 1 x 30 mg pediatric capsule given with high fat meal
Since ritlecitinib is rapidly eliminated (t½ ~2 hours), there will be at least a 48-hour washout 
between each dose.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoints
The primary endpoints are the plasma AUCinf (if data permit, otherwise AUClast) and Cmax of 
ritlecitinib. The test/reference ratios for AUCinf (if data permit), AUClast and Cmax will be 
derived with Treatments B, C, and D (pediatric capsules sprinkled in strawberry jam, 
pediatric capsules sprinkled in yoghurt, and pediatric capsules sprinkled in applesauce, 
respectively) as the test treatments and Treatment A (pediatric capsules) as the reference
treatment. In addition, the test/reference ratios for AUCinf (if data permit), AUClast and Cmax
will be derived with Treatment E (pediatric capsules given with high fat meal) as the test 
treatment and Treatment A (pediatric capsules) as the reference treatment.
PK parameters following a single dose administration will be derived from the 
concentration-time profiles using noncompartmental methods as data permit.  The various 
PK parameters to be assessed in this study, their definition, and method of determination are 
outlined in Table 3. In all cases, actual PK sampling times will be used in the derivation of 
PK parameters.






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For all periods, the baseline measurement is the latest measurement during the screening
period.
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to releasing the database and classifications will 
be documented per standard operating procedures.
Participant Analysis Set
Description
Safety Analysis Set
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention.  Participants 
will be analyzed according to the product they actually 
received.
PK Concentration Set
The PK concentration population is defined as all participants 
randomized and treated who have at least one concentration in 
at least 1 treatment period.
PK Parameter Set
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.
5. GENERAL METHODOLOGY AND CONVENTIONS
Final analysis will be performed after study participant data set release following last 
participant last visit.
5.1. Hypotheses and Decision Rules
No statistical hypothesis will be tested in this study.
5.2. General Methods
5.2.1. Analyses for Binary/Categorical Endpoints
For binary or categorical variables, number of participants, numbers and percentages of 
participants meeting the categorical criteria will be presented in accordance with the Clinical 
Data Interchange Standards Consortium and Pfizer Standards (CaPS).
5.2.2. Analyses for Continuous Endpoints
For continuous variables, the data will be summarized using the number of participants, 
mean, median, standard deviation (SD), minimum, and maximum in accordance with the 
CaPS. For appropriate PK parameters, geometric mean and geometric coefficient of variation 
(%CV) will also be summarized.


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5.3. Methods to Manage Missing Data
5.3.1. Pharmacokinetic Data
Methods to handle missing PK data are described below. 
Concentrations Below the Limit of Quantification:
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero. In listings, BLQ values will be reported as “<LLQ”, where LLQ 
will be replaced with the value for the lower limit of quantification.
Deviations, Missing Concentrations and Anomalous Values:
In summary tables and plots of median profiles, statistics will be calculated having set
concentrations to missing if one of the following cases is true:
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample).
2. A deviation in sampling time is of sufficient concern or a concentration has been
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
An anomalous concentration value is one that, after verification of bioanalytical validity, is 
grossly inconsistent with other concentration data from the same individual or from other 
participants. For example, a BLQ concentration that is between quantifiable values from the 
same dose is considered as anomalous. Anomalous concentration values may be excluded 
from PK analysis at the discretion of the PK analyst.
PK Parameters:
Actual PK sampling times will be used in the derivation of PK parameters. If a PK parameter 
cannot be derived from a participant’s concentration data, the parameter will be coded as NC 
(ie, not calculated). (Note that NC values will not be generated beyond the day that a 
participant discontinues).
In summary tables, statistics will not be presented for a particular treatment group if more 
than 50% of the data are NC. For statistical analyses, PK parameters coded as NC will also 
be set to missing.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to a dosing error or an unexpected event such as vomiting before all the compound is 
adequately absorbed from the gastrointestinal tract), this will be footnoted in summary tables 
and will not be included in the calculation of summary statistics or statistical analyses.  For 
instance, if a participant has a vomiting event post dose that is within a duration of time that 
is 2-times the derived median Tmax for the population for the administered treatment, then the 


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pharmacokineticist should consider the exclusion of the PK concentration data collected 
following the initial vomiting event in that treatment period and the PK parameter data 
reported for that treatment period from the datasets used to calculate summary statistics or 
statistical analyses.
5.3.2. Safety Data
Missing values in standard summaries of AEs and laboratory data will be imputed according 
to CaPS.
6. ANALYSES AND SUMMARIES
6.1. Primary Endpoints
AUCinf (if data permit), AUClast and Cmax will be summarized by treatment group and will 
include the set of summary statistics as specified in Table 4.
For the evaluation of relative bioavailability of pediatric ritlecitinib sprinkled in applesauce, 
yoghurt and strawberry jam relative to intact blend-in capsule of ritlecitinib, natural log 
transformed AUCinf (if data permit), AUClast and Cmax will be analyzed using a mixed effects
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% CI for the ratios. Treatment A (pediatric 
capsules) will be the Reference treatment and Treatments B, C, and D (pediatric capsules 
sprinkled in strawberry jam, pediatric capsules sprinkled in yoghurt, and pediatric capsules 
sprinkled in applesauce) will be the Test treatments.
For the evaluation of food effect on the bioavailability of the capsule dosage formulation of 
ritlecitinib, natural log transformed AUCinf (if data permit), AUClast and Cmax will be analyzed 
using a mixed effects model with sequence 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% CI for the ratios. 
Treatment A (pediatric capsules) will be the Reference treatment and Treatment E (pediatric 
capsules given with high fat meal) will be the Test treatment.
For AUCinf, AUClast and Cmax, a listing of the individual participant ratios (Test/Reference) 
will be provided. Box and whisker plots for AUCinf, AUClast and Cmax, will be plotted by 
treatment and overlaid with geometric means.
Residuals from the model will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals but these will not be included in the CSR. If there are major deviations from 
normality or outliers then the effect of these on the conclusions will be investigated through 


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alternative transformations and/or analyses excluding outliers. Justification for any 
alternative to the planned analysis will be given in the report of the study.
6.2. Secondary Endpoints
Analyses and summaries of safety data are described in Section 6.6.
6.3. Other Endpoints
6.3.1. Other PK parameters for ritlecitinib
Exploratory endpoints include other PK parameters for ritlecitinib such as Tmax, t1/2, CL/F 
and Vz/F. The PK parameters will be listed and summarized descriptively by treatment group 
in accordance with Pfizer data standards on the PK Parameter Analysis Set, as data permit. 
Missing values will be handled as detailed in Section 5.3.1. Each PK parameter will be 
summarized by treatment group and will include the set of summary statistics as specified in 
Table 4. 
Table 4.
PK Parameters to be Summarized Descriptively by Treatment 
Parameter
Summary Statistics
AUCinf, AUClast, Cmax, 
CL/F, Vz/F
N, arithmetic mean, median, SD, %CV, minimum, maximum, 
geometric mean and geometric %CV
Tmax
N, median, minimum, maximum
t½
N, arithmetic mean, median, SD, %CV, minimum, maximum
Supporting data from the estimation of t½ and AUCinf will be listed by analyte and group:
terminal phase rate constant (kel); goodness of fit statistic from the log-linear regression (r2);
the percent of AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of
time points used in the estimation of kel. This data may be included in the clinical study
report.
PK Concentrations:
The plasma concentrations will be listed and descriptively summarized by nominal PK 
sampling time and treatment. Individual participant, as well as mean and median profiles of 
the plasma concentration-time data will be plotted by treatment using actual (for individual) 
and nominal (for mean and median) times respectively. Mean and median profiles will be 
presented on both linear and semi-log scales.
Presentations of concentrations will include:

A listing of all concentrations sorted by participant ID, treatment and nominal time
postdose. The concentration listing will also include the actual times. Deviations from the 
nominal time will be given in a separate listing.




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6.5.2. Study Conduct and Participant Disposition
Participants evaluation groups will show end of study participant disposition. Frequency 
counts will be supplied for participant discontinuation(s) by treatment. Data will be reported 
in accordance with the CaPS.
6.5.3. Study Treatment Exposure
Study treatment exposure will be listed by sequence.
6.5.4. Concomitant Medications and Nondrug Treatments
All prior and concomitant medication(s) as well as non-drug treatment(s) will be reported in 
the listings.
6.6. Safety Summaries and Analyses
All safety analyses will be performed on the Safety Analysis Set.
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
6.6.1. Adverse Events
AEs will be reported in accordance with the CaPS.
Participant discontinuations due to adverse events will be detailed by treatment. Data will be 
reported in accordance with the CaPS.
6.6.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with the CaPS.
6.6.3. Vital Signs
Vital sign data will be databased and available upon request.
6.6.4. Electrocardiograms
ECG data will be databased and available upon request.
7. INTERIM ANALYSES
No formal interim analysis will be conducted for this study. As this is an open-label 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.
Final analysis will follow the official database release.  As this will be an open-label study, 
there is no formal unblinding of the randomization code.


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APPENDICES
Appendix 1. SAS Code for Analyses
An example of the PROC MIXED code is provided below:
For the primary objective – relative BA:
proc mixed data=tab.pk;
class seq period trt participant;
model l&var=seq period trt/ ddfm=KR;
random participant(seq) /subject=participant(seq);
lsmeans trt;
estimate 'B vs A' trt -1 1 0 0 0  /cl alpha=0.1;
estimate 'C vs A' trt -1 0 1 0 0  /cl alpha=0.1;
estimate 'D vs A' trt -1 0 0 1 0  /cl alpha=0.1;
ods 'Estimates' out=est&var;
ods 'lsmeans' out=ls&var;
ods 'covparms' out=cov&var;
ods 'tests3' out=tst&var;
run;
For the primary objective – food effect:
proc mixed data=tab.pk;
class seq trt participant;
model l&var=seq trt/ ddfm=KR;
random participant(seq) /subject=participant(seq);
lsmeans trt;
estimate 'E vs A' trt -1 0 0 0 1  /cl alpha=0.1;
ods 'Estimates' out=est&var;
ods 'lsmeans' out=ls&var;
ods 'covparms' out=cov&var;
ods 'tests3' out=tst&var;
run;
/* Letter assignments for treatments (trt) within the estimate statement above are as follows
Treatment A: ritlecitinib 1 x 30 mg pediatric capsule in fasted state (reference);
Treatment B: contents of ritlecitinib 1 x 30 mg pediatric capsule sprinkled on strawberry jam 
in fasted state (test);
Treatment C: contents of ritlecitinib 1 x 30 mg pediatric capsule sprinkled on yoghurt in 
fasted state (test);
Treatment D: contents of ritlecitinib 1 x 30 mg pediatric capsule sprinkled on applesauce in 
fasted state (test);
Treatment E: ritlecitinib 1 x 30 mg pediatric capsule given with high fat meal (test)
*/


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Appendix 2. List of Abbreviations
Abbreviation
Term
%CV
coefficient of variation
AA
alopecia areata
AE
adverse event
AUCextrap%
the percent of AUCinf based on extrapolation
AUCinf
area under the plasma concentration-time profile from time zero 
extrapolated to infinite time
AUClast
area under the plasma concentration-time profile from time zero to the 
time of the last quantifiable concentration
BA
bioavailability
BiC
blend-in capsule
BLQ
below the limit of quantitation
BP
blood pressure
CaPS
Clinical Data Interchange Standards Consortium and Pfizer Standards
CD
Crohn’s Disease
CI
confidence interval
Clast
last quantifiable concentration
CL/F
apparent clearance after oral dose
Cmax
maximum plasma concentration
CSR
clinical study report
ECG
electrocardiogram
HR
heart rate
kel
terminal phase rate constant
LLQ
lower limit of quantitation
mg
milligram
N/A
not applicable
NC
not calculated
ND
not done
NS
no sample
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PR
pulse rate
PR interval
time from the beginning of the P wave to the beginning of the QRS 
complex
QRS
Combination of Q-, R- and S- wave on an electrocardiogram representing 
ventricular depolarization
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
r2
goodness of fit statistic from the log-linear regression
RR
the time between the start of one QRS complex and the start of the next 
QRS complex
SAP
statistical analysis plan


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Abbreviation
Term
SD
single dose; standard deviation
SoA
schedule of activities
t½
terminal elimination half-life
TEAE
treatment emergent adverse event
Tmax
time for Cmax
UC
ulcerative colitis
Vz/F
apparent volume of distribution after oral dose