A PHASE 1, RANDOMIZED, OPEN-LABEL, CROSS-OVER, SINGLE DOSE STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF PEDIATRIC RITLECITINIB (PF-06651600) CAPSULES AND SPRAY CONGEALED BEADS RELATIVE TO ADULT CAPSULES IN HEALTHY ADULT PARTICIPANTS
Phase: PHASE1
Conditions: Healthy Participants
Sponsor: Pfizer

Ritlecitinib (PF-06651600) 
Protocol B7981030
Final Protocol Amendment 1, 11 August 2021
PFIZER CONFIDENTIAL
Page 1
A PHASE 1, RANDOMIZED, OPEN-LABEL, CROSS-OVER, SINGLE DOSE 
STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF PEDIATRIC 
RITLECITINIB (PF-06651600) CAPSULES AND SPRAY CONGEALED BEADS 
RELATIVE TO ADULT CAPSULES IN HEALTHY ADULT PARTICIPANTS
Study Intervention Number:
PF-06651600
Study Intervention Name:
Ritlecitinib
US IND Number:
EudraCT Number:
Not Applicable 
Protocol Number:
B7981030
Phase:
1
Short Title: RELATIVE BIOAVAILABILITY STUDY IN HEALTHY 
PARTICIPANTS OF PEDIATRIC RITLECITINIB (PF-06651600) CAPSULES 
AND SPRAY CONGEALED BEADS RELATIVE TO ADULT CAPSULES  
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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Final Protocol Amendment 1, 11 August 2021
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Amendment 1
11 August 2021
•
In Section 1.1 Synopsis, Section 1.3 
SOA, Section 3 Objectives and 
Endpoints, Section 4.1 Overall 
Design, Section 8.11 Taste 
Assessment, Section 9.4.4 Taste 
Assessment Analyses, added taste 
assessment as an “Other” endpoint.
Rationale: Spray congealed beads are 
a new formulation being evaluated. 
Taste assessment is included to enable 
evaluation of the taste characteristics. 
•
In Section 5.2, Exclusion Criterion 
#21, the eGFR cutoff was revised to 
<60 ml/min. 
Rationale: eGFR ≥60 ml/min is 
considered within the normal range 
per current Pfizer guidance for healthy 
participant studies. 
•
Added Appendix 9 Taste Assessment 
Questionnaire
Rationale: Taste Assessment
Questionnaire is the tool for assessing 
the taste characteristics of the spray 
congealed beads. 
•
Revised language in Section 2.2.4.3.3 
Phase 2a Study in Alopecia Areata
Rationale: To improve readability
Original protocol
12 October 2020
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs.
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................13
1.3. Schedule of Activities .............................................................................................14
2. INTRODUCTION ...............................................................................................................17
2.1. Study Rationale .......................................................................................................17
2.2. Background .............................................................................................................17
2.2.1. Nonclinical Pharmacology..........................................................................17
2.2.2. Nonclinical Pharmacokinetics and Metabolism .........................................17
2.2.3. Nonclinical Safety ......................................................................................17
2.2.4. Clinical Overview.......................................................................................18
2.2.4.1. Clinical Overview of Ritlecitinib..............................................18
2.2.4.2. Pharmacokinetic Overview of Ritlecitinib................................18
2.2.4.3. Safety Overview of Ritlecitinib.................................................18
2.3. Benefit/Risk Assessment.........................................................................................20
2.3.1. Risk Assessment.........................................................................................21
3. OBJECTIVES AND ENDPOINTS.....................................................................................23
4. STUDY DESIGN.................................................................................................................23
4.1. Overall Design.........................................................................................................23
4.2. Scientific Rationale for Study Design.....................................................................24
4.3. Justification for Dose ..............................................................................................25
4.4. End of Study Definition ..........................................................................................26
5. STUDY POPULATION......................................................................................................26
5.1. Inclusion Criteria.....................................................................................................26
5.2. Exclusion Criteria....................................................................................................27
5.3. Lifestyle Considerations..........................................................................................31
5.3.1. Meals and Dietary Restrictions...................................................................31
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................32
5.3.3. Activity .......................................................................................................32
5.3.4. Contraception..............................................................................................32
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5.3.5. Vaccination.................................................................................................33
5.4. Screen Failures ........................................................................................................33
6. STUDY INTERVENTION..................................................................................................33
6.1. Study Intervention(s) Administered........................................................................33
6.1.1. Administration............................................................................................34
6.2. Preparation/Handling/Storage/Accountability ........................................................34
6.2.1. Preparation and Dispensing........................................................................35
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................35
6.3.1. Allocation to Study Intervention ................................................................35
6.4. Study Intervention Compliance...............................................................................35
6.5. Concomitant Therapy..............................................................................................36
6.5.1. Rescue Medicine.........................................................................................36
6.6. Dose Modification...................................................................................................36
6.7. Intervention After the End of the Study..................................................................36
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................37
7.1. Discontinuation of Study Intervention ....................................................................37
7.2. Participant Discontinuation/Withdrawal From the Study.......................................37
7.2.1. Withdrawal of Consent...............................................................................38
7.3. Lost to Follow up ....................................................................................................38
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................39
8.1. Efficacy Assessments..............................................................................................40
8.2. Safety Assessments .................................................................................................40
8.2.1. Physical Examinations................................................................................40
8.2.2. Vital Signs ..................................................................................................41
8.2.2.1. Temperature ..............................................................................41
8.2.3. Electrocardiograms.....................................................................................41
8.2.4. Clinical Safety Laboratory Assessments ....................................................42
8.2.5. Estimated Glomerular Filtration Rate.........................................................43
8.2.6. Pregnancy Testing ......................................................................................43
8.3. Adverse Events and Serious Adverse Events..........................................................43
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......44
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8.3.1.1. Reporting SAEs to Pfizer Safety...............................................44
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................44
8.3.2. Method of Detecting AEs and SAEs ..........................................................45
8.3.3. Follow-up of AEs and SAEs.......................................................................45
8.3.4. Regulatory Reporting Requirements for SAEs...........................................45
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................45
8.3.5.1. Exposure During Pregnancy......................................................46
8.3.5.2. Exposure During Breastfeeding ................................................47
8.3.5.3. Occupational Exposure .............................................................48
8.3.6. Cardiovascular and Death Events...............................................................48
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................48
8.3.8. Adverse Events of Special Interest.............................................................48
8.3.8.1. Lack of Efficacy........................................................................48
8.3.9. Medical Device Deficiencies......................................................................48
8.3.10. Medication Errors.....................................................................................48
8.4. Treatment of Overdose............................................................................................49
8.5. Pharmacokinetics ....................................................................................................50
8.6. Pharmacodynamics..................................................................................................50
8.7. Genetics...................................................................................................................51
8.7.1. Specified Genetics ......................................................................................51
8.7.2. Banked Biospecimens for Genetics............................................................51
8.8. Biomarkers ..............................................................................................................51
8.9. Immunogenicity Assessments.................................................................................51
8.10. Health Economics .................................................................................................51
8.11. Taste Assessment ..................................................................................................51
9. STATISTICAL CONSIDERATIONS ................................................................................51
9.1. Statistical Hypotheses .............................................................................................52
9.2. Sample Size Determination.....................................................................................52
9.3. Analysis Sets ...........................................................................................................52
9.4. Statistical Analyses .................................................................................................53
9.4.1. Efficacy Analyses .......................................................................................53
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9.4.2. Safety Analyses ..........................................................................................53
9.4.3. Pharmacokinetic Analyses..........................................................................53
9.4.4. Taste Assessment Analyses ........................................................................55
9.4.5. Other Analyses............................................................................................55
9.5. Interim Analyses .....................................................................................................55
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............55
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................56
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............56
10.1.1. Regulatory and Ethical Considerations ....................................................56
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................56
10.1.2. Financial Disclosure .................................................................................57
10.1.3. Informed Consent Process........................................................................57
10.1.4. Data Protection .........................................................................................58
10.1.5. Dissemination of Clinical Study Data ......................................................58
10.1.6. Data Quality Assurance ............................................................................59
10.1.7. Source Documents....................................................................................61
10.1.8. Study and Site Start and Closure ..............................................................61
10.1.9. Publication Policy.....................................................................................62
10.1.10. Sponsor’s Qualified Medical Personnel .................................................62
10.2. Appendix 2: Clinical Laboratory Tests .................................................................64
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................65
10.3.1. Definition of AE .......................................................................................65
10.3.2. Definition of SAE.....................................................................................66
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................67
10.3.4. Reporting of SAEs....................................................................................70
10.4. Appendix 4: Contraceptive Guidance ...................................................................72
10.4.1. Male Participant Reproductive Inclusion Criteria....................................72
10.4.2. Female Participant Reproductive Inclusion Criteria.................................72
10.4.3. Woman of Childbearing Potential ............................................................72
10.4.4. Contraception Methods.............................................................................73
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10.5. Appendix 5: Genetics............................................................................................75
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........76
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................78
10.8. Appendix 8: Guidelines for Participant Safety Monitoring and 
Discontinuation..........................................................................................................80
10.8.1. Participant Safety Monitoring...................................................................80
10.8.2. Participant Discontinuation Criteria .........................................................81
10.9. Appendix 9: Taste Assessment Questionnaire......................................................83
10.10. Appendix 10: Abbreviations ...............................................................................91
11. REFERENCES ..................................................................................................................96
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LIST OF TABLES
Table 1.
Pharmacokinetic Sampling Schema for Period 1, Period 2 and 
Period 3.....................................................................................................16
Table 2.
Study Design and Treatments...................................................................24
Table 3.
Definitions of PK Parameters...................................................................53
Table 4.
Protocol-Required Safety Laboratory Assessments .................................64
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: RELATIVE BIOAVAILABILITY STUDY IN HEALTHY 
PARTICIPANTS OF PEDIATRIC RITLECITINIB (PF-06651600) CAPSULES AND 
SPRAY CONGEALED BEADS RELATIVE TO ADULT CAPSULES
Rationale
Ritlecitinib (PF-06651600) is a covalent and irreversible inhibitor of JAK3 with high 
selectivity over the other JAK isoforms (JAK1, JAK2, and TYK2).  Ritlecitinib 
(PF-06651600) also inhibits irreversibly the TEC family kinases with selectivity over the 
broader human kinome.  Treatment with ritlecitinib (PF-06651600) 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 (PF-06651600) 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.
A capsule formulation of the tosylate salt of ritlecitinib (PF-06651600) has been developed 
and nominated to be the marketed dosage form and is being evaluated in a pivotal BE trial 
relative to the tablets.  The tablet formulation is the current clinical product at strengths of 
10 mg and 50 mg.  A 10 mg capsule and a spray congealed bead are being evaluated as 
potential candidate formulations for pediatric patients.  Both these formulations have 
qualitative and quantitative differences in their formulation excipients from the adult 
capsules.  The primary objective of this study is to obtain an estimate of the bioavailability 
of a single oral dose of pediatric ritlecitinib (PF-06651600) capsules (3 × 10 mg capsules) 
relative to the 30 mg adult capsule in healthy adult participants under fasting conditions.  
Additionally, an alternative pediatric formulation utilizing a spray congealed beads will also 
be evaluated.
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Objectives and Endpoints
Objectives
Endpoints
Primary: 
Primary: 
•
To estimate the relative BA of ritlecitinib 
(PF-06651600) pediatric capsules (3 × 10 mg 
capsule, Test) relative to adult 30 mg capsule 
(Reference) under fasted conditions in healthy 
adult participants. 
•
To estimate the relative BA of ritlecitinib 
(PF-06651600) administered as 30 mg spray 
congealed beads (Test) relative to adult 30 mg 
capsule (Reference) under fasted conditions in 
healthy adult participants.    
•
Plasma AUCinf and Cmax for ritlecitinib 
(PF-06651600).
Secondary: 
Secondary: 
•
To evaluate the safety and tolerability of 10 mg 
capsules, 30 mg capsules and spray congealed 
beads at the 30 mg dose of ritlecitinib 
(PF-06651600) administered to healthy adult 
participants under fasted conditions.
•
Safety laboratory tests and AE monitoring. 
Other: 
Other: 
•
To characterize the PK of ritlecitinib 
(PF-06651600) administered as pediatric 
capsules (3 × 10 mg capsule), adult 30 mg 
capsule and 30 mg spray congealed beads in 
healthy adult participants under fasted 
conditions.
•
To assess the sensory characteristics and overall 
palatability of spray congealed beads by healthy 
participants.
•
Tmax, AUClast, t½ (if data permit) and other PK 
parameters such as CL/F, Vz/F.
•
Responses to the taste assessment questionnaire 
that document overall liking, mouth feel, 
bitterness, sourness, saltiness and tongue/mouth 
burn of sensory attributes.
Overall Design
The study will be conducted as a Phase 1, open-label, single dose, randomized, 3 period, 
cross-over design in a single cohort of approximately 12 healthy male or female participants 
at a single center.  Participants will be randomized into 2 sequences of treatment as 
described in the following table of Intervention Groups and Duration.
Number of Participants
A total of approximately 12 participants will be randomly assigned to study intervention such 
that approximately 6 participants will be enrolled to 1 of the 2 sequences. 
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Participants who withdraw from the study may be replaced at the discretion of the 
investigator upon consultation with the sponsor.
Intervention Groups and Duration
Treatment 
Sequence
Period 1
Washout
Period 2
Washout
Period 3
1 (n=6)
A
At least 2 days 
of washout 
between dosing
B
At least 2 days 
of washout 
between dosing
C
2 (n=6)
B
A
C
n = number of participants.
Treatment A: ritlecitinib (PF-06651600) 30 mg intact adult capsule
Treatment B: ritlecitinib (PF-06651600) 3 × 10 mg pediatric capsules 
Treatment C: ritlecitinib (PF-06651600) 30 mg spray congealed beads
Since ritlecitinib (PF-06651600) is rapidly eliminated (t½ ~2 hours), there will be at least a 
2-day washout between each dose. 
Blood samples for PK analysis will be collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 
12, 16 and 24 hours post-dose.
A taste assessment will be conducted using a taste assessment questionnaire for the spray 
congealed beads in Period 3, immediately after dosing, and at 5 min, 10 min, 20 min after 
dosing.  
Participants will participate in the study up to approximately 2.5 months, including the 
screening and follow-up periods.  Participants will be screened within 28 days of the first 
dose of study intervention and if all entry criteria are fulfilled, the participants will report to 
the CRU on the day prior to Period 1 Day 1 dosing (Day -1).  On Day 1 of each period, 
participants will receive a single dose of study intervention.  Capsules and spray congealed 
beads will be administered with approximately 240 mL of ambient temperature water and 
will be swallowed (not chewed). Participants will be fasted for at least 10 hours pre-dosing 
and 4 hours post-dosing.
Participants will be confined in the CRU for a total of at least 7 days (6 nights which includes 
admission to the CRU on Day -1) 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 interventions to capture any potential AE and confirm 
appropriate contraceptive usage.
Data Monitoring Committee or Other Independent Oversight Committee
Not Applicable.
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Statistical Methods
The following table presents the width of 90% confidence interval for different estimated 
effects for a sample size of 12 participants:
Parameter
Estimated Effect
(100*Test/Reference)
90%CI
CI Width
AUC
85%
77.0%, 93.9%
16.9%
90%
81.5%, 99.4%
17.9%
95%
86.0%, 104.9%
18.9%
100%
90.6%, 110.4%
19.9%
105%
95.1%, 115.9%
20.9%
110%
99.6%, 121.5%
21.9%
115%
104.1%, 127.0%
22.8%
Cmax
85%
69.7%, 103.6%
33.9%
90%
73.8%, 109.7%
36.9%
95%
77.9%, 115.8%
37.9%
100%
82.0%, 121.9%
39.9%
105%
86.1.6%, 128.0%
41.9%
110%
90.2%, 134.1%
43.9%
115%
94.3%, 140.2%
45.9%
These calculations are based on the estimates of within-subject standard deviations of 
0.106 and 0.212 for ritlecitinib (PF-06651600) loge AUCinf and loge Cmax, respectively, as 
obtained from studies B7981003 and B7981022. 
Participants may be replaced at the discretion of the sponsor.
To estimate the relative BA of ritlecitinib (PF-06651600) pediatric capsule (3 × 10 mg 
capsules) relative to adult 30 mg capsule, the 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 (30 mg capsule form of ritlecitinib [PF-06651600] under fasted conditions) will be the 
Reference treatment while Treatment B (3 × 10 mg pediatric capsules of ritlecitinib 
[PF-06651600] under fasted conditions) will be the Test treatment.  Data from Period 3 
(Treatment C) will be excluded from this analysis.
To estimate the relative BA of ritlecitinib (PF-06651600) administered as 30 mg spray 
congealed beads (Test) relative to adult 30 mg capsule (Reference) under fasted conditions, 
the 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 
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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 (30 mg capsule of ritlecitinib 
[PF-06651600] under fasted conditions) will be the Reference treatment while Treatment C 
(30 mg spray congealed beads of ritlecitinib [PF-06651600] under fasted conditions) will be 
the Test treatment.
Taste Assessment Analyses
The data used in the analysis will be transcribed and rescaled to a score from 0 to 100 from 
the raw measurements on the taste questionnaire.  The sensory attributes (overall liking, 
mouth feel, bitterness, sourness, saltiness, tongue/mouth burn) from the taste questionnaire 
(Appendix 9) for Treatment C (30 mg spray congealed beads) will be listed and descriptively 
summarized by collection time. Radar plots for each time point, summarizing all attributes, 
will be generated.
1.2. Schema
Not Applicable.
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 10
Screeninga
Treatment Period
Period 1
Period 2
Period 3
Follow-upb
Early 
Termination/
Discontinuation
Days Relative to Day 1
Day -28 to 
Day -2
Day -1
Day 1
Day 2
Day 1
Day 2
Day 1
Day 2
Telephone 
Contact 
Study Day
-28 to -2
-1
1
2
3
4
5
6
33 to 40
Informed consent
X
CRU confinement
X
→
→
→
→
→
X
Inclusion/exclusion criteria
X
Xc
Demographic informationd
X
Medical/medication, drug, 
tobacco and alcohol history 
(update)e
X
Xc
Complete/limited physical 
examinationf
X
X
X
X
Safety laboratoryg
X
X
X
X
Pregnancy test (WOCBP 
only)
X
X
X
X
Contraception checkh
X
X
X
X
X
FSH (post-menopausal 
women only)
X
Urine drug testing
X
X
12-Lead ECGi
X
Xo
X
X
Blood pressure and pulse 
rate, temperaturej
X
Xo
X
X
HIV, HCVAb, HBsAg, 
HbcAbk
X
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Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 10
Screeninga
Treatment Period
Period 1
Period 2
Period 3
Follow-upb
Early 
Termination/
Discontinuation
Days Relative to Day 1
Day -28 to 
Day -2
Day -1
Day 1
Day 2
Day 1
Day 2
Day 1
Day 2
Telephone 
Contact 
Study Day
-28 to -2
-1
1
2
3
4
5
6
33 to 40
TB screening 
(QuantiFERON® Gold 
Test)
X
Lipid panelg
X
Study intervention 
administrationl
X
Xp
Xp
Taste assessment
Xq
Pharmacokinetic blood 
samplingm
X
X
X
X
X
X
Pfizer Prep D1 Banked 
Genetic Biospecimensn
Xo
Prior/concomitant 
treatments
X
X
X
X
X
X
CRU discharge 
X
Serious and nonserious 
adverse event monitoring
X
X
→
→
→
→
→
X
X
X
a.
Participants will be screened within 28 days of the first dose of study intervention.
b.
Follow-up contact will occur by telephone and must occur at least 28 to 35 days after the last administration of ritlecitinib (PF-06651600).
c.
Update since screening, if applicable.
d.
Including measurement of height and weight at screening.
e.
Include history of alcohol abuse, tobacco/nicotine containing products, licit and illicit drug use or dependence within 6 months of Screening. For Day -1, records would be 
reviewed or updated only.
f.
Complete (full) physical examination must either be conducted at Screening or upon Admission of Period 1 (Day -1) only; limited physical examination is required upon 
discharge/early termination/discontinuation; brief (limited) physical examination may be performed as appropriate at other times at the investigator’s discretion if there are 
findings during the previous examination, new/open adverse events.
g.
Safety laboratory testing must be collected within 28 days prior to first administration of study medication (see Section 8.2.4).  Safety laboratory assessments including 
urinalysis, hematology, and chemistry will be performed following at least 4 hours fasting; however, the lipid profile requires fasted conditions for at least 10 hours.  
Samples will be collected prior to discharge or if the reason for discontinuation is related to an AE.  Additional laboratory assessments may be required to evaluate 
potential case of Hy’s Law or adverse event as deemed necessary by the investigator. Refer to Table 4 in Section 10.2.  
h.
The contraception check is an opportunity to confirm that contraception, if assigned, is used consistently and correctly. 
i.
Single ECG will be used.
j.
Single BP will be collected in the supine position.
k.
For hepatitis B, all participants will undergo testing at screening for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb); If HBsAg is negative and 
HBcAb is positive, HBsAb should be evaluated.
l.
Participants assigned to receive study intervention under fasted conditions must be fasted for at least 10 hours pre-dosing and 4 hours post-dosing.
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Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 10
Screeninga
Treatment Period
Period 1
Period 2
Period 3
Follow-upb
Early 
Termination/
Discontinuation
Days Relative to Day 1
Day -28 to 
Day -2
Day -1
Day 1
Day 2
Day 1
Day 2
Day 1
Day 2
Telephone 
Contact 
Study Day
-28 to -2
-1
1
2
3
4
5
6
33 to 40
m.
PK dosing will be captured on the day of dosing at the following timepoints: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
n.
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a participant visit.
o.
Collected at pre-dose.
p.
Dosing of each period to be separated by at least a 48-hour washout interval. The participants will be discharged on Day 2 of Period 3.
q.
Review taste assessment questionnaire and instructions with participants prior to dosing in Period 3, Day 1. Each participant will record the sensory attributes at timed 
intervals of 0 (immediately after dosing), 5, 10 and 20 minutes after administration using a taste assessment questionnaire (see Appendix 9).  
Table 1.
Pharmacokinetic Sampling Schema for Period 1, Period 2 and Period 3
Visit Identifier
Period 1, Period 2 and Period 3
Study Day
1
2
Hours Before/After Dose
0a
0.25
0.5
1
1.5
2
3
4
6
9
12
16
24
Study Intervention Administration
X
Ritlecitinib (PF-06651600) PK 
blood samplingb
X
X
X
X
X
X
X
X
X
X
X
X
X
a.
Predose PK samples. Any time prior to dosing ritlecitinib (PF-06651600) on the day of dosing.
b.
Ritlecitinib (PF-06651600) PK blood samples (2 mL blood to yield approximately 0.5 mL plasma) are to be collected.
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2. INTRODUCTION
Ritlecitinib (PF-06651600) 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 proposed pediatric formulation for ritlecitinib (PF-06651600) is a 10 mg capsule 
administered intact or sprinkled over food.  The primary objective of this study is to obtain 
an estimate of the bioavailability of pediatric ritlecitinib (PF-06651600) capsules relative to 
the adult capsule in healthy participants.  Also, an alternative formulation utilizing spray 
congealed beads will be evaluated. 
2.2. Background 
Ritlecitinib (PF-06651600) is a covalent and irreversible inhibitor of JAK3 with high 
selectivity over the other JAK isoforms (JAK1, JAK2, and TYK2).  Ritlecitinib 
(PF-06651600) also inhibits irreversibly the tyrosine kinase expressed in TEC family kinases 
with selectivity over the broader human kinome.  Treatment with ritlecitinib (PF-06651600) 
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 (PF-06651600) 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 (PF-06651600) can be found in the 
current IB.
2.2.2. Nonclinical Pharmacokinetics and Metabolism
Details of the nonclinical PK and metabolism of ritlecitinib (PF-06651600) 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 44-fold exposure multiple in the rat 
study and a 6.5-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 central 
nervous system and the peripheral nervous system at ≥20 mg/kg/day, accompanied by 
functional auditory deficits (brainstem auditory evoked potentials ) at the highest dose of 
40 mg/kg/day (a 29-fold exposure multiple relative to the clinical dose of 50 mg).
Further information is available in the current version of the ritlecitinib (PF-06651600) IB. 
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2.2.4. Clinical Overview
2.2.4.1. Clinical Overview of Ritlecitinib
Ritlecitinib (PF-06651600) has been evaluated in healthy participants in a FIH B7981001
study, in a BA B7981003 study which compared the relative BA of solution versus tablet, 
and a PK study in Japanese participants (B7981008).  It has also been evaluated in 
participants with moderate to severe RA in B7981006, and moderate to severe AA in 
B7931005.  Study B7981022 compared the relative BA of capsule versus tablet.  Besides, 
there are ongoing studies in participants with moderate to severe AA (B7981015), moderate 
to severe active UC (B7981005), active non-segmental vitiligo (B7981019), and moderate to 
severe active CD (B7981007). 
2.2.4.2. Pharmacokinetic Overview of Ritlecitinib
The PK profile of ritlecitinib (PF-06651600) is characterized by rapid absorption, rapid 
elimination (terminal half-life [t½] of ~2 hours) and are approximately dose proportional.  
Steady state generally appears to have been reached by Day 4 for the QD regimens and 
Day 6 for the BID regimens based on similar median trough (pre-dose) ritlecitinib 
(PF-06651600) beyond Day 6.  Ritlecitinib (PF-06651600) 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 
(PF-06651600) in humans appear to be primarily by metabolism.  Less than 10% of 
ritlecitinib (PF-06651600) is excreted unchanged in the urine.
2.2.4.3. Safety Overview of Ritlecitinib
2.2.4.3.1. Studies in Healthy Participants
The FIH study (B7981001) was a Phase 1, randomized, double-blind, third party open, 
placebo controlled, single and multiple dose escalation, parallel group study in healthy adult 
participants.  During the single dose period, participants received doses of 5, 20, 50, 100, 
200, 400, or 800 mg of ritlecitinib (PF-06651600) in a dose escalation format.  Participants 
returned for the multiple dose period to receive doses of 50, 200, or 400 mg QD or 100 or 
200 mg BID for 14 days.
B7981008 study was a Phase 1, randomized, double-blind, third–party open, 
placebo-controlled study to evaluate the safety, tolerability, PK and PD after multiple oral 
doses of ritlecitinib (PF-06651600) in healthy Japanese adult participants.  Six participants 
were randomized, with 2 participants receiving placebo and 4 participants receiving 
ritlecitinib (PF-06651600) 200 mg QD, respectively. 
B7981003 was a Phase 1, open label, single-dose 3-way crossover study to evaluate the 
relative BA of a solid dose formulation of ritlecitinib (PF-06651600) under fasting conditions 
and the effect of a high fat meal on the BA of the solid dosage formulation of ritlecitinib 
(PF-06651600) in healthy participants.  A total of 14 participants were randomized to study 
treatment.
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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 (PF-06651600).  Each study included 12 to 14 healthy 
participants.
In all the above studies, ritlecitinib (PF-06651600) was found to be well tolerated and to have 
an acceptable safety profile.
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, multi-center 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 (PF-06651600).  Participants remained on stable background arthritis therapy, 
which had to include methotrexate (supplemented with folic/folinic acid per the local 
treatment guidelines).
Ritlecitinib (PF-06651600) 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 (PF-06651600) compared to those receiving placebo.  The TEAEs 
reported in more than 5% (1 in 20) participants with RA receiving ritlecitinib (PF-06651600) 
were influenza and lymphopenia.  The majority of the AEs were mild in severity.  There 
was 1 mild case of herpes simplex in the ritlecitinib (PF-06651600) group that was 
considered to be treatment -related with no cases in the placebo group.  There were no 
clinically relevant changes in vital signs, ECG, or audiometric assessments.  By the Week 8 
time point (as early as 2 weeks), in the ritlecitinib (PF-06651600) group, there were 
decreases in the median platelet counts (25% change from baseline), lymphocyte counts 
(21% change from baseline), neutrophil counts (24% change from baseline), and hemoglobin 
(3% change from baseline).  None of these were deemed to be clinically relevant by the 
investigator and values returned to near baseline by the 12-week follow-up visit.
2.2.4.3.3. Phase 2a Study 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 (PF-06651600) and 
PF-06700841 (a TYK2/JAK1 inhibitor) 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; 47 participants received placebo, 
48 participants received ritlecitinib (PF-06651600), and 47 participants received 
PF-06700841.
During the initial 24-week double-blind treatment period, participants in the ritlecitinib 
(PF-06651600) group were treated with 200 mg of ritlecitinib (PF-06651600) QD during a 
4-week induction phase, followed by dosing with 50 mg QD in a maintenance phase.  At 
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Week 24, an interim analysis provided data on both efficacy and safety, and indicated clinical 
improvement for participants treated with ritlecitinib (PF-06651600).
During the initial 24-week treatment period of Study B7931005, there were no deaths and no 
participant in the ritlecitinib (PF-06651600) treatment group experienced a SAE.  The 
proportion of participants who experienced TEAEs in the placebo treatment group (74.5%) 
was comparable with the ritlecitinib (PF-06651600) treatment group (62.5%).  The TEAEs 
reported in more than 5% (1 in 20) participants with AA receiving ritlecitinib (PF-06651600) 
were headache, infections of upper respiratory tract, acne, diarrhea, nausea, and skin 
infections.  The majority of events were mild.  No serious infections, malignancies, cases 
of herpes zoster, or cases of herpes simplex were reported in the ritlecitinib (PF-06651600) 
group.  Hematological changes were observed in both active groups during the induction 
and maintenance periods, but were not associated with clinically relevant TEAEs.  During 
the induction period, when participants received ritlecitinib (PF-06651600) 200 mg QD for 
4 weeks, decreases in mean platelet and lymphocyte counts (-18% and -24% mean change 
from baseline, respectively) were observed in the ritlecitinib (PF-06651600) group.  During 
the maintenance period, when participants received 50 mg QD for 20 weeks, there was 
improvement in the platelet and lymphocyte counts in the ritlecitinib (PF-06651600) group.  
Neutrophil counts were increased at Week 4 (12% change from baseline) and Week 24 (10% 
change from baseline) in the ritlecitinib (PF-06651600) treatment group.  Two participants 
in the ritlecitinib (PF-06651600) group discontinued due to TEAEs.
In addition to the initial 24-week period, the trial included two extensions. Extension 1 was 
an SBE Period in which the participants had treatment withdrawn and were then re-treated 
for up to 24 weeks with the initially assigned IP after the participants reached a pre-specified 
retreatment criterion (ie, 30% hair loss from the regrown hair at Week 24).  The second 
extension was a CO Open Label Extension Period in which the Week 24 non-responders 
were assigned the opposite active treatment than the one received in the initial (Week 0-24) 
treatment period.  There were no SUSARs, serious infections, adverse events of QTcF 
prolongation, malignancies and/or no case of herpes zoster during the extension periods.
More detailed information about ritlecitinib (PF-06651600) can be found in in the current 
version of the ritlecitinib (PF-06651600) IB, which is the SRSD for this study.
2.3. Benefit/Risk Assessment
Ritlecitinib (PF-06651600) 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 
JAK3 development.  In this study, ritlecitinib (PF-06651600) will be administered at single 
doses of 30 mg.
Ritlecitinib (PF-06651600) was determined to be well tolerated and to have an acceptable 
safety profile in the clinical studies.  Reductions in platelet counts and lymphocyte counts 
were observed during treatment with 200 mg QD, but were not considered clinically 
meaningful and improved after switching to 50 mg QD.  Ritlecitinib (PF-06651600) 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 
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infection will be monitored in this study and evaluated in longer term studies of ritlecitinib 
(PF-06651600).  
In animals, ritlecitinib (PF-06651600) was associated with fetal changes in bones and some 
internal organs, and lower fetal body weights.  It is not known whether ritlecitinib 
(PF-06651600) is secreted into human milk. Because of that and because of the 
investigational nature of ritlecitinib (PF-06651600), 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 (PF-06651600) is not likely to transfer to a partner through 
semen at pharmacologically relevant blood levels.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of ritlecitinib (PF-06651600) may be found in the IB, which is 
SRSD for this study. 
Overall, single doses of ritlecitinib (PF-06651600) of 30 mg in healthy participants are 
expected to be safe and well tolerated in this study.
2.3.1. Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
Study Intervention ritlecitinib (PF-06651600)
Reductions in platelet counts and
lymphocyte counts.
In B7931005 study, reductions
in platelet counts and
lymphocyte counts were
observed during treatment with
200 mg QD, but were not
considered clinically meaningful
and improved after switching to
50 mg QD.
Clinical laboratory results will be
monitored.
Potential risk of infections.
Ritlecitinib (PF-06651600) is an
immunomodulator and, as such,
can be associated with the
potential risk of infections
(including serious infections),
opportunistic infections, and
viral reactivation.
Participants with infection history
will be excluded (See Section 5.2)
and the risk of infection will be
monitored in the study.
Potential fetal risk.
In animals, ritlecitinib 
(PF-06651600) was
associated with fetal changes
in bones and some internal
organs, and lower fetal body
weights.
When male rats were treated
with ritlecitinib (PF-06651600)
and mated with female rats that
WOCBP who are unwilling or
unable to use contraception as
defined in the study protocol will
be excluded (See Section 5.3.4.
and Appendix 4).
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Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
Study Intervention ritlecitinib (PF-06651600)
were not treated, there were
smaller litter sizes due to fewer
fertilized eggs attaching to the
wall of the uterus in those
female rats.  There were no
effects on sperm or other
features of male reproduction.
Potential risk of secreting into
human milk.
It is not known whether
ritlecitinib (PF-06651600) is
secreted into human milk.
Ritlecitinib (PF-06651600) should
not be administered to
breastfeeding women and
exposure during breastfeeding
should be reported to Pfizer Safety
(See Section 8.3.5.2).
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3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 
•
To estimate the relative BA of ritlecitinib 
(PF-06651600) pediatric capsules (3 × 10 mg 
capsule, Test) relative to adult 30 mg capsule 
(Reference) under fasted conditions in healthy 
adult participants. 
•
To estimate the relative BA of ritlecitinib 
(PF-06651600) administered as 30 mg spray 
congealed beads (Test) relative to adult 30 mg 
capsule (Reference) under fasted conditions in 
healthy adult participants.    
•
Plasma AUCinf and Cmax for ritlecitinib 
(PF-06651600).
Secondary: 
Secondary: 
•
To evaluate the safety and tolerability of 10 mg 
capsules, 30 mg capsules and spray congealed 
beads at the 30 mg dose of ritlecitinib 
(PF-06651600) administered to healthy adult 
participants under fasted conditions.
•
Safety laboratory tests and AE monitoring. 
Other: 
Other: 
•
To characterize the PK of ritlecitinib 
(PF-06651600) administered as pediatric 
capsules (3 × 10 mg capsule), adult 30 mg 
capsule and 30 mg spray congealed beads in 
healthy adult participants under fasted 
conditions.
•
To assess the sensory characteristics and overall 
palatability of spray congealed beads by healthy 
participants.
•
Tmax, AUClast, t½ (if data permit) and other PK 
parameters such as CL/F, Vz/F.
•
Responses to the taste assessment questionnaire 
that document overall liking, mouth feel, 
bitterness, sourness, saltiness and tongue/mouth 
burn of sensory attributes.
4. STUDY DESIGN
4.1. Overall Design
The study will be conducted as a Phase 1, open-label, single dose, randomized, 3 period, 
cross-over design in a single cohort of approximately 12 healthy male or female participants 
at a single center.  Participants will be randomized into 2 sequences of treatment as 
described in Table 2:
Sequence 1 (n=6): A  B  C
Sequence 2 (n=6): B  A  C
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Table 2.
Study Design and Treatments
Treatment 
Sequence
Period 1
Washout
Period 2
Washout
Period 3
1 (n=6)
A
At least 2 days 
of washout 
between dosing
B
At least 2 days 
of washout 
between dosing
C
2 (n=6)
B
A
C
n = number of participants.
Treatment A: ritlecitinib (PF-06651600) 30 mg intact adult capsule
Treatment B: ritlecitinib (PF-06651600) 3 × 10 mg pediatric capsules 
Treatment C: ritlecitinib (PF-06651600) 30 mg spray congealed beads
Since ritlecitinib (PF-06651600) is rapidly eliminated (t½ ~2 hours), there will be at least a 
48-hour washout between each dose. 
Blood samples for PK analysis will be collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 
12, 16 and 24 hours post-dose.
Participants will participate in the study up to approximately 2.5 months, including the 
screening and follow-up periods.  Participants will be screened within 28 days of the first 
dose of study intervention and if all entry criteria are fulfilled, the participants will report to 
the CRU on the day prior to Period 1 Day 1 dosing (Day -1).  On Day 1 of each period, 
participants will receive a single dose of study intervention.  Capsules and spray congealed 
beads will be administered with approximately 240 mL of ambient temperature water, and 
will be swallowed (not chewed).  Participants will be fasted for at least 10 hours pre-dosing 
and 4 hours post-dosing.
For the taste assessment in Period 3, participants will be asked to not verbalize their 
responses and not discuss taste with other participants until after they have filled out the 
responses in the questionnaire.
Participants will be confined in the CRU for a total of at least 7 days (6 nights which includes 
admission to the CRU on Day -1) 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 interventions to capture any potential AE and confirm 
appropriate contraceptive usage.
Participants who withdraw from the study may be replaced at the discretion of the sponsor.
4.2. Scientific Rationale for Study Design
A capsule formulation of the tosylate salt of ritlecitinib (PF-06651600) has been developed 
and nominated to be the marketed dosage form and is being evaluated in a pivotal BE trial 
relative to the tablets.  The tablet formulation is the current clinical product at strengths of 
10 mg and 50 mg.  A 10 mg capsule and a spray congealed bead are being evaluated as 
potential candidate formulations for pediatric patients.  Both these formulations have 
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qualitative and quantitative differences in their formulation excipients from the adult 
capsules.  
The intent of the study is to estimate the relative bioavailability of ritlecitinib (PF-06651600) 
10 mg capsule that is being developed as the market image/commercial pediatric drug 
product.  An alternate dosage form, spray congealed beads, will also be evaluated for 
bioavailability relative to the adult 30 mg capsules.  The spray congealed beads is being 
considered as an alternative pediatric formulation. 
In an embryo-fetal development study in rats, skeletal malformations and variations and 
lower fetal body weights were observed at relevant clinical exposures for ritlecitinib 
(PF-06651600). In rabbits, lower mean fetal body weights and higher incidences of visceral 
and skeletal malformations and skeletal variations were observed at relevant clinical 
exposures for PF-06651600. See the IB for further details. Therefore, the use of a highly
effective method of contraception is required in WOCBP (see Appendix 4).  
The potential risk of exposure to ritlecitinib (PF-06651600) in a sexual partner of a male 
participant in this study via ejaculate is low, and therefore no contraception use in male 
participants is required.  The calculated safety margin is ≥100-fold between the estimated 
partner exposure due to seminal transfer and the NOAEL for serious manifestations of 
developmental toxicity in nonclinical studies.  The safety margin of 100-fold is based on 
applying a 10-fold safety factor for interspecies extrapolation and a 10-fold safety factor for 
susceptible populations.1
Banked Biospecimens will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
The current study will use ritlecitinib (PF-06651600) at a dose of 30 mg which is the lowest 
strength available for the reference adult capsules.  The 30 mg dose of ritlecitinib 
(PF-06651600) is a clinically relevant dose.
Based on clinical data (single oral doses of ritlecitinib [PF-06651600] 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).  The AUC 
for a ritlecitinib (PF-06651600) 200 mg dose maintains the margins of 14-fold and 2.5-fold 
to NOAELs in 2-month and 9-month dog toxicology studies, respectively.
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.  Hence, ritlecitinib (PF-06651600) is predicted to be 
well tolerated at a dose of 30 mg in this relative bioavailability study.  Further information 
is available in the current version of the ritlecitinib (PF-06651600) IB.
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4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last scheduled 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.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of 
signing the ICD.
•
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Male and female participants who are healthy as determined by medical evaluation 
including a detailed medical history, complete (full) physical examination, which 
includes BP and pulse rate measurement, clinical laboratory tests, and 12-lead ECG.
3. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight: 
4. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). 
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Informed Consent:
5. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, 
dermatological, or allergic disease (including drug allergies, but excluding untreated, 
asymptomatic, seasonal allergies at the time of dosing).
2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).  
3. Known immunodeficiency disorder, including positive serology for HIV at screening, 
or a first degree relative with a hereditary immunodeficiency.
4. Infection with hepatitis B or hepatitis C viruses according to protocol specific testing 
algorithm.
a.
For hepatitis B, all participants will undergo testing for HBsAg and HBcAb.  
•
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:
i.
If HBsAb is negative, the participant must be excluded from 
participation in the study;
ii.
If HBsAb is positive, the participant is eligible for study inclusion.
b.
For hepatitis C, all participants will undergo testing for HCVAb. Only 
participants who are HCVAb negative are eligible.
5. Participants with any of the following acute or chronic infections or infection history:
•
Any infection requiring treatment within 2 weeks prior to admission for Period 1.
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•
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.
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.
8. 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.
9. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
10. Have evidence of untreated or inadequately treated active or latent Mycobacterium 
TB infection as evidenced by the following:
•
A positive QuantiFERON®-TB Gold In-Tube (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.
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o
A participant who is currently being treated for active or latent TB infection 
must be excluded from the study.
Prior/Concomitant Therapy:
11. 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 6.5 for additional details).
12. Use of medications that prolong the QT interval (a list of these medications can be 
found at http://www.crediblemeds.org/index.php/login/dlcheck) within 10 days or 
5 half-lives (whichever is longer) prior to the first dose of the study intervention, or 
during the study.
13. Vaccination with live virus, attenuated live virus, or any live viral components 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:
14. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of study intervention 
used in this study (whichever is longer).
15. Known participation in a clinical trial of ritlecitinib (PF-06651600) and participant 
experienced treatment-related adverse events that led to discontinuation or an SAE. 
Diagnostic Assessments:
16. A positive urine drug test.
17. A positive serum pregnancy test.
18. 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.
19. Baseline 12-lead ECG that demonstrates:
•
Clinically significant abnormalities requiring treatment (eg, acute myocardial 
infarction, serious tachy- or bradyarrhythmias) or indicating serious 
underlying heart disease (eg, cardiomyopathy, Wolff Parkinson–White 
syndrome);
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•
Complete LBBB, signs of an acute or indeterminate age myocardial 
infarction, ST-T interval changes suggestive of myocardial ischemia, second  
or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias; 
•
Confirmed QTcF prolongation (>450 milliseconds).  If QTc exceeds 
450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more 
times and the average of the 3 QTc or QRS values should be used to 
determine the participant's eligibility.  Computer interpreted ECGs should be 
overread by a physician experienced in reading ECGs before excluding 
participants.
20. Long QT Syndrome, a family history of Long QT Syndrome, or a history of 
Torsades de Pointes.
21. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat test, if deemed necessary: 
•
AST or ALT level >1.5 × ULN;
•
Total bilirubin level >1.5 × ULN; participants with Gilbert's syndrome would be 
eligible for this study provided that direct bilirubin is ≤ULN;
•
Hemoglobin level <120 g/L (12.0 g/dL);
•
Platelet count <150 × 109/L (150,000 cells/mm3);
•
WBC count of <3.0 × 109/L (3000 cells/mm3);
•
ANC <1.5 × 109/L (<1500 cells/mm3);
•
ALC <0.8 × 109/L (<800 cells/mm3);
•
eGFR <60 mL/min/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 that could affect interpretation of study 
data or the participant's participation in the study.
Other Exclusions:
22. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening.  Binge drinking is defined as a pattern of 
5 (male) and 4 (female) or more alcoholic drinks in about 2 hours.  As a general 
rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces [240 mL] 
beer, 1 ounce [30 mL] of 40% spirit or 3 ounces [90 mL] of wine).
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23. Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.
24. Have a history of major organ transplant or hematopoietic stem cell/marrow 
transplant.  Skin grafts are not exclusionary.
25. History of severe allergic or anaphylactic reactions. 
26. WOCBP who are unwilling or unable to use a highly effective 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.
27. Females on HRT and whose menopausal status is in doubt.
28. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing.  
29. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol. 
30. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members. 
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Meals and Dietary Restrictions
•
Participants must abstain from all food and drink (except water) at least 10 hours 
prior to screening laboratory evaluations and at least 4 hours prior to any subsequent 
safety laboratory evaluations and 10 hours prior to the collection of the predose PK 
sample on Day 1 of each Period. 
•
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.  Fasting prior to 
clinical laboratory sample collection may be extended beyond 4 hours, as needed.  
•
Lunch will be provided approximately 4 hours after dosing.
•
Dinner will be provided approximately 9 to 10 hours after dosing.
•
An evening snack may be permitted.
•
Participants will be allowed breakfast on Day 2 of each period.
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•
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.
5.3.2. Caffeine, Alcohol, and Tobacco
•
Participants will abstain from caffeine containing products for 24 hours prior to the 
start of dosing and during confinement in the CRU.  
•
Participants will abstain from alcohol for 24 hours prior (or as specified above for red 
wine) to admission to the CRU and continue abstaining from alcohol 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.  
5.3.3. Activity
•
Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests.  Walking at a normal pace will be permitted.
•
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.
5.3.4. Contraception 
No contraception methods are required for male participants in the study.
The following applies to female participants who are considered WOCBP.
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant from the permitted list of contraception methods (see Appendix 4 Section 10.4.4) 
and will confirm that the participant has been instructed in its consistent and correct use.  At 
time points indicated in the SoA, the investigator or designee will inform the participant of 
the need to use highly effective contraception consistently and correctly and document the 
conversation and the participant’s affirmation in the participant’s chart (participants need to 
affirm their consistent and correct use of at least 1 of the selected methods of contraception).  
In addition, the investigator or designee will instruct the participant to call immediately if the 
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selected contraception method is discontinued or if pregnancy is known or suspected in the 
participant or partner.
5.3.5. Vaccination
Vaccination with live virus, attenuated live virus, or any live viral components is prohibited 
within the 6 weeks prior to the first dose of study intervention, during the study, and for 
6 weeks after the last dose of study intervention.  Similarly, current routine household 
contact with individuals who have been vaccinated with live vaccine components should be 
avoided during treatment and for 6 weeks following completion of treatment.  Following 
vaccination with live component vaccines, 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).
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 to the clinical database.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened if prior reason for not meeting the eligibility criteria has been resolved.  
Rescreening may only occur with Sponsor approval.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to ritlecitinib (PF-06651600) 
10 mg pediatric capsule, ritlecitinib (PF-06651600) 30 mg adult capsule, and ritlecitinib 
(PF-06651600) 30 mg spray congealed beads.
6.1. Study Intervention(s) Administered
For this study, the study intervention is ritlecitinib (PF-06651600), which will be 
administered as capsules and sprayed congealed beads. The study intervention will be 
supplied to the CRU in bulk along with individual dosing containers for unit dosing.
Ritlecitinib (PF-06651600) will be presented to the participants in individual dosing 
containers.
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6.1.1. Administration
Study intervention will be administered orally and according to the conditions described in 
SoA and Meals and Dietary Restrictions of this protocol.
Following an overnight fast of at least 10 hours, participants will receive study intervention 
at approximately 0800 hours (plus or minus 2 hours).  Investigator site personnel will 
administer study intervention during each period with ambient temperature water to a total 
volume of approximately 240 mL.  Participants will swallow the study intervention whole, 
and will not manipulate or chew the study intervention prior to swallowing.  Administer 
study intervention according to the IP Manual. 
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/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken.  The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible.  Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention.  Specific details regarding the definition of an 
excursion and information the site should report for each excursion will be provided 
to the site in the IP manual.   
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. See the IP manual for storage conditions of the study intervention.
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7. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent.  All study interventions will be accounted for 
using a study intervention accountability form/record.  
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual.  All destruction must be adequately 
documented.  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery, as described in the IP Manual.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff.  Dispensing is defined as the provision of study intervention, concomitant treatments, 
and accompanying information by qualified staff member(s) to a healthcare provider or
participant in accordance with this protocol.  Local health authority regulations or 
investigator site guidelines may use alternative terms for these activities.
Ritlecitinib (PF-06651600) capsules and spray congealed beads will be prepared at the CRU 
in the individual dosing containers, by 2 operators, one of whom is an appropriately qualified 
and experienced member of the study staff (eg, physician, nurse, physician’s assistant, nurse 
practitioner, pharmacy assistant/technician, or pharmacist).  Prepared doses will be provided 
in unit dose containers and labeled in accordance with Pfizer regulations and the clinical 
site’s labeling requirements.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
The investigator will assign participant numbers to the participants as they are screened for 
the study.  Pfizer will provide a randomization schedule to the investigator and, in 
accordance with the randomization numbers, the participant will receive the study treatment 
regimen assigned to the corresponding randomization number.
6.4. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF.  
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The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site. Study site personnel will examine each 
participant’s mouth to ensure that the study intervention was ingested.
6.5. Concomitant Therapy
Participants will abstain from all concomitant treatments, except for the treatment of AEs. 
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.
Use of medications that prolong the QT interval (a list of these medications can be found at 
http://www.crediblemeds.org/index.php/login/dlcheck) are prohibited within 10 days or 
5 half-lives (whichever is longer) prior to the first dose of the study intervention, or during 
the study. 
Vaccination with live virus, attenuated live virus, or any live viral components are prohibited 
within the 6 weeks prior to the first dose of study intervention. (Refer to Section 5.3.5 for 
additional details).
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.  Concomitant drug and non-drug treatment 
will be collected.  All participants will be questioned about concomitant treatment at each 
clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment.  Treatments taken after the first dose of study intervention 
will be documented as concomitant treatments.
6.5.1. Rescue Medicine 
There is no rescue therapy to reverse the AEs observed with ritlecitinib (PF-06651600); 
standard medical supportive care must be provided to manage the AEs. 
6.6. Dose Modification 
Dose modification for ritlecitinib (PF-06651600) is not allowed. 
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation).  Reasons for definitive discontinuation of study 
intervention include the following: treatment-related SAEs, serious infections, and other 
events as described in Section 10.8.2.
Note that discontinuation of study intervention does not represent withdrawal from the study.  
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for 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 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information. 
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:
•
Refused further follow-up;
•
Lost to follow-up;
•
Death;
•
Study terminated by sponsor;
•
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 
both from the study intervention and from the study at that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
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If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the CT SAE Report.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 
and/or posttreatment study follow-up, and entered on the appropriate CRF page.  In the 
event that vital status (whether the participant is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed 
in accordance with local law.
7.3. Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
•
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;
•
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods).  These contact attempts should be documented 
in the participant’s medical record;
•
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
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8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention 
to confirm that they meet the study population criteria for the study.  If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.
A participant who qualified for this protocol but did not enroll from an earlier cohort/group 
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study.  In 
addition, other clinical assessments or specimen collections, eg, banked biospecimens, may 
be used without repeat collection, as appropriate.
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICD may be utilized for screening or baseline
purposes provided the procedures met the protocol specified criteria and were performed 
within the time frame defined in the SoA.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety 
and well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
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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 
110 mL (PK sample volume calculated as approximately 78 mL).  The actual collection 
times of blood sampling may change.  Additional blood samples may be taken for safety 
assessments at times specified by Pfizer, provided the total volume taken during the study 
does not exceed 550 mL during any period of 60 consecutive days.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.
8.1. Efficacy Assessments
Not Applicable.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled 
clinical laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
For safety assessments, baseline is defined as the last predose measurement taken before 
dosing in Period 1: safety laboratory (Day -1), blood pressure, pulse rate, temperature and 
12-Lead ECG (Day 1, predose).
8.2.1. Physical Examinations
A complete (full) physical examination will be completed only at the Screening visit or upon 
admission to the clinic (Day -1) and will include, at a minimum, head, ears, eyes, nose, 
mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, 
musculoskeletal, and neurological systems. 
A brief (limited) physical examination is required upon discharge/early 
termination/discontinuation and will include, at a minimum, assessments of general 
appearance, the respiratory and cardiovascular systems, and participant-reported symptoms. 
Brief (limited) physical examination may also be performed as appropriate at other times at 
the investigator’s discretion if there are findings during the previous examination, new/open 
AEs.
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. 
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8.2.2. Vital Signs
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest.  The same arm 
(preferably the dominant arm) will be used throughout the study.  Participants should be 
instructed not to speak during measurements.  
The same properly sized and calibrated BP cuff will be used to measure BP each time.  The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds.  When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection. 
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
8.2.2.1. Temperature 
Temperature will be measured orally.  No eating, drinking, or smoking is allowed for 
15 minutes prior to the measurement.
8.2.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS 
complex.  Alternative lead placement methodology using torso leads (eg, Mason-Likar) is 
not recommended given the potential risk of discrepancies with ECGs acquired using 
standard limb lead placement.  All scheduled ECGs should be performed after the 
participant has rested quietly for at least 10 minutes in a supine position. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline (Period 1, Day 1 predose) measurements.  Additional ECG 
monitoring will occur if a) a postdose QTc interval is increased by ≥60 msec from the 
baseline and is >450 msec; or b) an absolute QTc value is ≥500 msec for any scheduled 
ECG.  If either of these conditions occurs, then 2 additional ECGs will be collected 
approximately 2 to 4 minutes apart to confirm the original measurement.  If the QTc values 
from these repeated ECGs remain above the threshold value, then a single ECG must be 
repeated at least hourly until QTc values from 2 successive ECGs fall below the threshold 
value that triggered the repeat measurement.
If a) a postdose QTc interval remains ≥60 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner, 
at the discretion of the investigator); or c) QTc intervals get progressively longer, the 
participant should undergo continuous ECG monitoring.  A cardiologist should be consulted 
if QTc intervals do not return to less than the criterion listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator).
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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 QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.4. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency.  All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.  
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 calendar day after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury. 
Participants may undergo random urine drug testing at the discretion of the investigator.  
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
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8.2.5. Estimated Glomerular Filtration Rate
eGFR will be calculated using the following equation developed by the CKD-EPI, which 
utilizes SCr: 
CKD-EPI 
•
If female and SCr is ≤0.7 mg/dL:
GFR (mL/min/1.73 m2) = 144 × (SCr/0.7) – 0.329 × 0.993age (× 1.159, if black).
•
If female and SCr is >0.7 mg/dL:
GFR (mL/min/1.73 m2) = 144 × (SCr/0.7) – 1.209 × 0.993age (× 1.159, if black).
•
If male and SCr is ≤0.9 mg/dL:
GFR (mL/min/1.73 m2) = 141 × (SCr /0.9) – 0.411 × 0.993age (× 1.159, if black).
•
If male and SCr is >0.9 mg/dL:
GFR (mL/min/1.73 m2) = 141 × (SCr /0.9) – 1.209 × 0.993age (× 1.159, if black). 
8.2.6. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in WOCBP at the times listed in the SoA.  
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior the participant’s receiving the study intervention.  Pregnancy tests will also be done 
whenever 1 menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the end of the study.  Pregnancy tests may also be 
repeated if requested by IRBs/ ECs or if required by local regulations.  
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
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In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days after the last administration of the study intervention.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AE or SAE after the participant has concluded 
study participation.  However, if the investigator learns of any SAE, including a death, at 
any time after a participant has completed the study, and he/she considers the event to be 
reasonably related to the study intervention, the investigator must promptly report the SAE to 
Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3.  The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
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8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  
The sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
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8.3.5.1. Exposure During Pregnancy
An EDP occurs if:  
•
A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.
•
A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure.  Below is an example of 
environmental exposure during pregnancy:  
•
A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion or skin contact.
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.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, 
the reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
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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 liveborn baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs.  Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 
•
Spontaneous abortion including miscarriage and missed abortion;
•
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents 
that the participant was given the Pregnant Partner Release of Information Form to provide to 
his partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 
•
A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.
•
A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure).  An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.  
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred.  The 
information must be reported using the CT SAE Report Form.  When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF.  However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use.  However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
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8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE.  Such persons 
may include healthcare providers, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness regardless of whether there is an associated SAE.  The information 
must be reported using the CT SAE Report Form.  Since the information does not pertain to 
a participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events 
Not Applicable
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not Applicable
8.3.8. Adverse Events of Special Interest 
Not Applicable
8.3.8.1. Lack of Efficacy 
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies 
Not Applicable
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.  
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
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Medication errors include:
•
Medication errors involving participant exposure to the study intervention;
•
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of ritlecitinib (PF-06651600) greater than 800 mg within a 24-hour 
time period will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities 
for at least 5 half-lives or 28 calendar days after the overdose of ritlecitinib 
(PF-06651600) (whichever is longer).
3. Document the quantity of the excess dose as well as the duration of the overdose 
in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis within 4 days from the date of the last dose 
of study intervention if requested by the medical monitor (determined on a case by 
case basis).  
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
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8.5. Pharmacokinetics 
Blood samples of approximately 2 mL, to provide approximately 0.5 mL plasma, will be 
collected for measurement of plasma concentrations of ritlecitinib (PF-06651600) 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). 
Samples will be used to evaluate the PK of ritlecitinib (PF-06651600).  Samples collected 
for analyses of ritlecitinib (PF-06651600) concentration may also be used to evaluate safety 
or efficacy aspects related to concerns arising during or after the study, for metabolite 
identification and/or evaluation of the bioanalytical method, or for other internal exploratory 
purposes.
Genetic analyses will not be performed on these plasma samples.  Participant confidentiality 
will be maintained.
Samples collected for measurement of plasma concentrations of ritlecitinib (PF-06651600) 
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.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
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8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.7.2. Banked Biospecimens for Genetics
A 4-mL blood sample optimized for DNA isolation Prep D1 will be collected as local 
regulations and IRBs/ECs allow. 
Banked Biospecimens may be used for research related to the study intervention(s).  Genes 
and other analytes (eg, proteins, RNA, nondrug metabolites) may be studied using the banked 
samples. 
See Appendix 5: Genetics for information regarding genetic research.  Details on processes 
for collection and shipment of these samples can be found in lab manual and other supporting 
documentation.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Immunogenicity Assessments
Immunogenicity assessments are not applicable in this study.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.11. Taste Assessment
Taste assessment of the spray congealed beads will be conducted in Period 3 with the aid of a 
questionnaire (Appendix 9). The taste assessment questionnaire will be administered to 
participants by trained staff using a colored copy of the questionnaire.
Participants after 
drug administration will be asked to rate the overall liking, mouth feel, bitterness, sourness, 
saltiness and tongue/mouth burn. The participants will rate the above immediately after 
dosing and at 5 min, 10 min, 20 min after dosing.
See Appendix 9 for the details about the taste assessment questionnaire.  
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in the SAP, which will be maintained by the sponsor.  
The SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
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9.1. Statistical Hypotheses
No statistical hypothesis will be tested in this study.
9.2. Sample Size Determination
The following table presents the width of 90% confidence interval for different estimated 
effects for a sample size of 12 participants:
Parameter
Estimated Effect
(100*Test/Reference)
90%CI
CI Width
AUC
85%
77.0%, 93.9%
16.9%
90%
81.5%, 99.4%
17.9%
95%
86.0%, 104.9%
18.9%
100%
90.6%, 110.4%
19.9%
105%
95.1%, 115.9%
20.9%
110%
99.6%, 121.5%
21.9%
115%
104.1%, 127.0%
22.8%
Cmax
85%
69.7%, 103.6%
33.9%
90%
73.8%, 109.7%
36.9%
95%
77.9%, 115.8%
37.9%
100%
82.0%, 121.9%
39.9%
105%
86.1.6%, 128.0%
41.9%
110%
90.2%, 134.1%
43.9%
115%
94.3%, 140.2%
45.9%
These calculations are based on the estimates of within-subject standard deviations of 
0.106 and 0.212 for ritlecitinib (PF-06651600) loge AUCinf and loge Cmax, respectively, as 
obtained from studies B7981003 and B7981022. 
Participants who discontinue or withdraw from the study or who are not considered evaluable 
may be replaced at the discretion of the sponsor.
9.3. 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.
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9.4. 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.
9.4.1. Efficacy Analyses
An efficacy analysis is not applicable to this study. 
9.4.2. 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.  Safety data will be presented in tabular 
and/or graphical format and summarized descriptively, where appropriate.
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.
For safety assessments, baseline is defined as the last predose measurement taken before 
dosing in Period 1: safety laboratory (Day -1), blood pressure, pulse rate, temperature and 
12-Lead ECG (Day 1, predose).
9.4.3. Pharmacokinetic Analyses
PK parameters following a single dose administration will be derived from the concentration
time profiles using non-compartmental 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.
Table 3.
Definitions of PK Parameters
Parameter
Definition
Method of Determination
AUClast
Area under the plasma concentration time 
profile from time 0 to the time of the last 
quantifiable concentration (Clast)
Linear-log trapezoidal method
AUCinf
Area under the plasma concentration-time 
profile from time 0 extrapolated to infinite 
time
AUClast + (Clast/kel) 
where Clast is the predicted plasma 
concentration at the last quantifiable time point 
estimated from the log-linear regression 
analysis
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Table 3.
Definitions of PK Parameters
Parameter
Definition
Method of Determination
Cmax
Maximum plasma concentration
Observed directly from the data
Tmax
Time for Cmax
Observed directly from the data as time of first 
occurrence
t½ 
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
Tlast
The time for Clast
Observed directly from the data
The plasma PK parameters in Table 3 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.
To estimate the relative BA of ritlecitinib (PF-06651600) pediatric capsule (3 × 10 mg 
capsules) relative to adult 30 mg capsule, the 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 (30 mg capsule form of ritlecitinib [PF-06651600] under fasted conditions) will be the 
Reference treatment while Treatment B (3 × 10 mg pediatric capsules of ritlecitinib 
[PF-06651600] under fasted conditions) will be the Test treatment.  Data from Period 3 
(Treatment C) will be excluded from this analysis.
To estimate the relative BA of ritlecitinib (PF-06651600) administered as 30 mg spray 
congealed beads (Test) relative to adult 30 mg capsule (Reference) under fasted conditions, 
the 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 
provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% 
confidence intervals for the ratios.  Treatment A (30 mg capsule of ritlecitinib 
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[PF-06651600] under fasted conditions) will be the Reference treatment while Treatment C 
(30 mg spray congealed beads of ritlecitinib [PF-06651600] under fasted conditions) will be 
the Test treatment.
9.4.4. Taste Assessment Analyses
The data used in the analysis will be transcribed and rescaled to a score from 0 to 100 from 
the raw measurements on the taste questionnaire.  The sensory attributes (overall liking, 
mouth feel, bitterness, sourness, saltiness, tongue/mouth burn) from the taste assessment
questionnaire (Appendix 9) for Treatment C (30 mg spray congealed beads) will be listed and 
descriptively summarized by collection time. Radar plots for each time point, summarizing 
all attributes, will be generated.
9.4.5. Other Analyses
Pharmacogenomic sample will be collected and retained for future analyses, but will not be 
analyzed, specifically, for this study. 
9.5. 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. 
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will not use a DMC. 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
•
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;
•
Applicable ICH GCP guidelines;
•
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the 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.
The investigator will be responsible for the following:
•
Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;
•
Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;
•
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
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10.1.2. Financial Disclosure
Investigators and sub investigators 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 his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study.  The participant should be given 
sufficient time and opportunity to ask questions and to decide whether or not to participate in 
the trial.
Participants must be informed that their participation is voluntary.  Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, HIPAA requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant.
Participants who are rescreened are required to sign a new ICD.
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Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research.  The optional 
additional research does not require the collection of any further samples.  The investigator 
or authorized designee will explain to each participant the objectives of the additional 
research.  Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period.  A separate 
signature will be required to document a participant's agreement to allow specimens to be 
used for additional research.  Participants who decline to participate in this optional 
additional research will not provide this separate signature.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site will be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code.  Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred.  All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code.  The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record identification.  
In case of data transfer, the sponsor will protect the confidentiality of participants’ personal 
data consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations.  In addition, Pfizer reports study results outside of the requirements of 
local laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
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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
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website.  Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods.  Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data.  Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance 
with applicable privacy laws and regulations.  CSRs will have personally identifiable 
information redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator 
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is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the IQMP.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will 
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promptly provide copies of the inspection findings to the sponsor or its agent.  Before 
response submission to the regulatory authorities, the investigator will provide the sponsor or 
its agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the Source Document Locator.
Description of the use of computerized system is documented in the Source Document 
Locator.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the CRO if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:
•
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;
•
Inadequate recruitment of participants by the investigator;
•
Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
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the reason for termination or suspension, as specified by the applicable regulatory 
requirements.  The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement.  If there is any 
conflict between the contract and this protocol, the contract will control as to termination 
rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submit all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and 
to provide comments and the investigator will, on request, remove any previously 
undisclosed confidential information before disclosure, except for any study- or 
Pfizer-intervention related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, 
the sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the CTMS. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention 
identifiers, participant numbers, contact information for the investigator site, and contact 
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details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 
problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  For sites other than a Pfizer CRU, the contact number is not 
intended for use by the participant directly, and if a participant calls that number, he or she 
will be directed back to the investigator site.
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests (Table 4) will be performed at times defined in the SoA
section of this protocol.  Additional laboratory results may be reported on these samples as a 
result of the method of analysis or the type of analyzer used by the clinical laboratory, or as 
derived from calculated values.  These additional tests would not require additional 
collection of blood.  Unscheduled clinical laboratory measurements may be obtained at any 
time during the study to assess any perceived safety concerns.
Table 4.
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
CKh
eGFR (CKD-EPI [serum 
Creatinine based])
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya
Urine drug 
screeningb
Pregnancy test (ꞵ-
hCG)c
At Screening Only
FSHd
HBsAge
HBcAbe
HCVAbe
HIV
QuantiFERON- TB 
Gold Testf
Lipid Panelg
a. Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
b. At Screening and Admission.  The minimum requirement for drug screening includes cocaine, THC, 
opiates/opioids, benzodiazepines, and amphetamines (others are site and study specific).
c. Serum β-hCG for female participants of childbearing potential.
d. At Screening for confirmation of postmenopausal status only.
e. If HBsAg is negative and HBcAb is positive, HBsAb should be evaluated.
f. Complete at screening.  Previous testing for QuantiFERON TB Gold Test will be accepted if completed 
within 12 weeks prior to screening.  Otherwise should be completed at screening and results available prior 
to Day 1.
g. Lipid panel tests include LDL (calculated), HDL, triglycerides and total cholesterol, and require fasted 
conditions for at least 10 hours.
h. In addition to re-testing creatine kinase >3 × ULN, urine myoglobin will be performed as reflex testing for 
any participant with creatine kinase >10 × ULN.
Investigators must document their review of each laboratory safety report.
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition
•
An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not
considered related to the study intervention.
•
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator.  Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE:
•
Is associated with accompanying symptoms;
•
Requires additional diagnostic testing or medical/surgical intervention;
•
Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.
•
Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent.  Such overdoses should be reported regardless of 
sequelae.
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Events NOT Meeting the AE Definition
•
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.
•
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
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d. Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
•
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:
•
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition.  These events 
should usually be considered serious.
•
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
•
Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are 
considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel.  Such cases are also 
considered for reporting as product defects, if appropriate.
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF
and for reporting serious adverse events on the CT SAE Report Form to Pfizer Safety.  
These requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; 
and (3) exposure to the study intervention under study during pregnancy or breastfeeding, 
and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must 
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be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours 
of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under 
study during pregnancy 
or breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (and EDP 
supplemental form for 
EDP)  
Note:  Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.
•
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.
•
The investigator will then record all relevant AE/SAE information in the CRF.
•
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.
•
There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety.  In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.
•
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
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•
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.
•
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.
•
Severe: An event that prevents normal everyday activities.  An AE that is assessed 
as severe should not be confused with an SAE.  Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality
•
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.
•
A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.
•
The investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.
•
The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.
•
For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.
•
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
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•
If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor.  In addition, if the investigator determines 
that an SAE is associated with study procedures, the investigator must record this 
causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the CT SAE Report Form and in accordance 
with the SAE reporting requirements.
Follow-up of AEs and SAEs
•
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.
•
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology. 
•
New or updated information will be recorded in the originally completed CRF.
•
The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool
•
The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool.
•
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.
•
The site will enter the SAE data into the electronic system as soon as the data 
become available.
•
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
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has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via CT SAE Report Form
•
Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.
•
In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service.
•
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.
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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
•
No contraception methods are required for male participants in this study, as the 
calculated safety margin is ≥100-fold between the estimated maternal exposure due to 
seminal transfer of ritlecitinib (PF-06651600) and the NOAEL for serious 
manifestations of developmental toxicity in nonclinical studies.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:
•
Is not a WOCBP (see definitions below in Section 10.4.3).
OR
•
Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described below,
during the intervention period and for at least 28 days after the last dose of study 
intervention, which corresponds to the time needed to eliminate any reproductive 
safety risk of the study intervention(s).  The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
intervention.
•
A WOCBP agrees not to donate eggs (ova, oocytes) for the purpose of reproduction 
during this period.  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;
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•
Documented bilateral salpingectomy;
•
Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female.
•
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  In addition:
•
A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 
•
A female on HRT and whose menopausal status is in doubt will be excluded 
from the study.
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.
Males
No contraception methods are required for male participants in the study.
Females
The following applies to female participants who are considered WOCBP.
Highly Effective Contraceptive Methods
1. Oral, injectable, or 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.
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5. Oral, intravaginal, transdermal, or injectable combined (estrogen- and progestogen-
containing) hormonal contraception associated with inhibition of ovulation used in 
combination with a barrier method. 
Acceptable barrier methods include:
•
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).
6. Vasectomized partner.
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has been 
confirmed.  If not, an additional highly effective method of contraception should be 
used.  The spermatogenesis cycle is approximately 90 days.
7. Sexual abstinence.
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant.
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10.5. Appendix 5: Genetics
Use/Analysis of DNA
•
Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease.  Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis.
•
The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or 
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.
•
The samples may be analyzed as part of a multistudy 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:
•
Samples for banking 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 Banked 
Biospecimens 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.  
•
Banked Biospecimens will be labeled with a code.  The key between the code and 
the participant’s personally identifying information (eg, name, address) will be held at 
the study site and will not be provided to the sample bank.
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI.  
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks.  The increase in TBili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample).  In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased.  This occurrence is still regarded as a 
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:
•
Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.
•
For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
•
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
•
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
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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 TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, CK, direct and indirect 
bilirubin, GGT, PT/INR, total bile acids, and alkaline phosphatase.  Consideration should 
also be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood 
for further testing, as needed, for further contemporaneous analyses at the time of the 
recognized initial abnormalities to determine etiology.  A detailed history, including 
relevant information, such as review of ethanol, acetaminophen/paracetamol (either by itself 
or as a coformulated product in prescription or over-the-counter medications), recreational 
drug, supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  
Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary 
tract) and collection of serum samples for acetaminophen/paracetamol drug and/or protein 
adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s 
law) cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as AEs
•
Marked sinus bradycardia (rate <40 bpm) lasting minutes.
•
New PR interval prolongation >280 msec.
•
New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from 
baseline.
•
New-onset atrial flutter or fibrillation, with controlled ventricular response rate: 
ie, rate <120 bpm.
•
New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ 
duration.
•
Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive 
ventricular complexes.
ECG Findings That May Qualify as SAEs
•
QTcF prolongation >500 msec.
•
New ST-T changes suggestive of myocardial ischemia.
•
New-onset left bundle branch block (QRS >120 msec).
•
New-onset right bundle branch block (QRS >120 msec).
•
Symptomatic bradycardia. 
•
Asystole:
•
In awake, symptom-free participants in sinus rhythm, with documented 
periods of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an 
escape rhythm that is below the AV node. 
•
In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 
•
Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.
•
Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).
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•
Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm 
(heart rate <40 bpm), accelerated idioventricular rhythm (HR >40 bpm to 
<100 bpm), and monomorphic/polymorphic ventricular tachycardia (HR 
>100 bpm (such as torsades de pointes)).
•
Type II second-degree (Mobitz II) AV block.
•
Complete (third-degree) heart block.
ECG Findings That Qualify as SAEs
•
Change in pattern suggestive of new myocardial infarction. 
•
Sustained ventricular tachyarrhythmias (>30 seconds’ duration).
•
Second- or third-degree AV block requiring pacemaker placement.
•
Asystolic pauses requiring pacemaker placement.
•
Atrial flutter or fibrillation with rapid ventricular response requiring 
cardioversion.
•
Ventricular fibrillation/flutter.
•
At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.
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10.8. Appendix 8: Guidelines for Participant Safety Monitoring and Discontinuation
These guidelines for participant safety monitoring and discontinuation are to be applied to all 
participants in Study B7981030.  Additional individual participant monitoring is at the 
discretion of the investigator and dependent on any perceived safety concerns.  
Unscheduled clinical labs may be obtained at any time during the study to assess such 
concerns, and a participant may be withdrawn at any time at the discretion of the 
investigator.
10.8.1. Participant Safety Monitoring
All potential treatment-related events of rash will be followed up until resolution or 
agreement with Pfizer. 
In the case of a positive pregnancy test, the participant will have study intervention 
interrupted and a serum sample collected on the same day (or as soon as possible) and 
submitted to the laboratory for pregnancy testing.
The following laboratory abnormalities require retesting until resolution or agreement 
with Pfizer:
Laboratory Variable
Laboratory Value
Re-testing 
Timeframe
Hematology
Absolute Neutrophil 
Count
<1000/mm3 (<1.0 × 109/L)
Within 48 hours
Hemoglobin
<10.0 g/dL (<6.21 mmol/L or <100 g/L) 
OR
Decrease of ≥2.0 g/dL from baseline
Within 48 hours
Platelet count
<100,000/mm3 (<100.0 × 109/L)
Within 48 hours
Absolute Lymphocyte 
Counta
<600/mm3 (<0.6 × 109/L)
Within 48 hours
Serum Chemistry
Creatine kinasea
>3 × ULN
Within 48 hours
Aspartate 
aminotransferase
See Section 10.6 Appendix 6 for potential cases of drug 
induced liver injury. 
Within 48 hours
Alanine 
aminotransferase
See Section 10.6 Appendix 6 for potential cases of drug 
induced liver injury. 
Within 48 hours
Total bilirubin
See Section 10.6 Appendix 6 for potential cases of drug 
induced liver injury. 
Within 48 hours
a.
In addition to re-testing creatine kinase >3 × ULN, urine myoglobin will be performed as reflex testing 
for any participant with creatine kinase >10 × ULN. 
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10.8.2. Participant Discontinuation Criteria
Treatment will be discontinued and the participant withdrawn from this study for:
Adverse Events:
•
Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy or hospitalization for treatment or meeting other 
criteria that require the infection to be classified as serious adverse event;
•
Treatment related SAEs;
•
Other serious or severe AEs, at the discretion of the investigator or sponsor.
ECG Abnormalities
•
Confirmed QTcF >500 milliseconds;
•
Confirmed increase from baseline in QTcF of >60 milliseconds.
Laboratory Abnormalities:
•
All the following laboratory abnormalities require discontinuation if they are 
confirmed:
•
Absolute Neutrophil Count <750/mm3 (<0.75 × 109/L);
•
Hemoglobin <9.0 g/dL (<5.59 mmol/L or <90 g/L) or a decrease of >30% from 
baseline (either criterion or both);
•
Platelet count <75,000/mm3 (<75.0 × 109/L);
•
Absolute Lymphocyte Count <500/mm3 (<0.5 × 109/L);
•
Creatine kinase >10 × ULN.
NOTE: In addition to retesting creatine kinase >3 × ULN, urine myoglobin will 
be performed as reflex testing for any participant with creatine kinase 
>10 × ULN.
•
AST or ALT that meet ANY of the following:
•
>3 times ULN with at least one total bilirubin value >2 times ULN;
•
>3 times ULN accompanied by signs or symptoms consistent with hepatic 
injury (eg, new onset elevated PT/INR); 
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•
Two sequential AST or ALT elevations >5 times ULN, regardless of total 
bilirubin or accompanying signs or symptoms.
NOTE: In each case, there is a need for additional investigations, such as 
review of ethanol, recreational drug and dietary supplement consumption; 
testing for acute hepatitis A, B or C infection and biliary tract imaging should 
be promptly discussed with the sponsor or designee.
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10.9. Appendix 9: Taste Assessment Questionnaire
1. The questionnaire should be administered to adult participants, preferably by the 
trained staff.  The clinical staff is trained by the CRU clinical coordinator for 
performing the taste assessment questionnaire and regarding the specific study 
restrictions.
2. Use a colored copy of the questionnaire.  
3. Do not alter (reduce or enlarge) the original size of the questionnaire.
4. Participants will be asked as much as possible to not verbalize their responses and not 
discuss taste with other participants until after they have filled out the responses in the 
questionnaire.
5. Please collect the following background information: 
Background Information
Study number / Study Site
Study Period and Day
Participant identification (ID) (Rand ID)
Formulation ID
Collection Date
Collection Time
Name of trained staff administering the 
questionnaire
Questionnaire fully completed
Yes / No
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Example: How to provide a mark (±) on the color bar and how to calculate the score.
In visual analogue scores, the length of the bar might be different from page to page when printed off. Scores 
should be calculated as follows:  
1.
Measure the length of the bar on the printed page (for example 11 cm).
2.
Measure the placement of the “X” (distance from the top of the bar) (for example 7 cm from the top). 
3.
Calculate the relative placement of the “X” (for example 7 cm/11 cm).  This is the score. 
This allows for a more accurate measurement of “X” regardless of the actual length of the bar on the printed 
page.
±
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Questionnaire:
Q1. Overall Liking – please tell us how much you like or dislike the product you tasted 
by providing a mark ( ± ) on the color bar:
“Immediately” refers to immediately after dosing
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Q2. Mouth feel – please tell us about the mouthfeel (such as grittiness, stickiness, 
waxiness) of the product you tasted by providing a mark ( ± ) on the color bar:
“Immediately” refers to immediately after dosing
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Q3. Bitterness – please tell us about the degree of bitterness of the product you tasted 
by providing a mark ( ± ) on the color bar:
“Immediately” refers to immediately after dosing
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Q4. Sourness – please tell us about the degree of Sourness of the product you tasted by 
providing a mark ( ± ) on the color bar:
“Immediately” refers to immediately after dosing
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Q5. Saltiness – please tell us about the degree of saltiness of the product you tasted by 
providing a mark ( ± ) on the color bar:
“Immediately” refers to immediately after dosing
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Q6. Tongue/Mouth Burn – please tell us about the degree of tongue/mouth burn you 
experienced after you tasted the product by providing a mark ( ± ) on the color bar:
“Immediately” refers to immediately after dosing
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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
AE
adverse event
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
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
BA
bioavailability
BE
bioequivalence
β-hCG
beta-human chorionic gonadotropin
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 Collaboration
Clast
last quantifiable concentration
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Abbreviation
Term
CL/F
apparent clearance after oral dose
Cmax
maximum plasma concentration
CO
Cross-Over
CO2
carbon dioxide (bicarbonate)
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
CT
clinical trial
CTMS
clinical trial management system
DCT
data collection tool
DILI
drug induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EBV
Epstein Barr Virus
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDP
exposure during pregnancy
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FIH
first in human
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GGT
gamma glutamyl transferase
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
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Abbreviation
Term
HBsAg 
hepatitis B surface antigen
HCVAb
hepatitis C antibody
HDL
high-density lipoprotein
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IL
interleukin
IND
investigational new drug 
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IQMP
Integrated Quality Management Plan
IRB
institutional review board
JAK
Janus kinase 
kel
terminal phase rate constant
LBBB
left bundle branch block
LDL
low-density lipoprotein
LFT
liver function test
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MMR
measles mumps rubella
msec
millisecond
N/A
not applicable
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Abbreviation
Term
NOAEL
no-observed-adverse-effect level
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PPD
purified protein derivative
PT
prothrombin time
PVC
premature ventricular contraction/complex
QD
once daily
QFT-G
QuantiFERON®-TB Gold In-Tube
QRS
time from ECG Q wave to the end of the S wave corresponding to 
ventricle depolarization
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
RA
rheumatoid arthritis
RAND
randomization
RBC
red blood cell
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SBE
Single-Blind Extension
SCr
serum creatinine
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBili
total bilirubin
TEAE
treatment-emergent adverse events
TEC
tyrosine kinase expressed in hepatocellular carcinoma
THC
tetrahydrocannabinol
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Abbreviation
Term
Tlast
The time for Clast
Tmax
time for maximum plasma concentration
TYK
tyrosine kinase
t½
terminal elimination half-life
UC
ulcerative colitis
ULN
upper limit of normal
US
United States
Vz/F
apparent volume of distribution after oral dose
WBC
white blood cell
WOCBP
woman of childbearing potential
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11. REFERENCES
1. Banholzer ML, Wandel C, Barrow P, et al. Clinical trial considerations on male 
contraception and collection of pregnancy information from female partner: update. Clin 
Transl Med 2016;5(1):23 37.
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