Clinical trial NCT04260464
Conditions: Healthy Volunteer Renal Impairment
Keywords: Pharmacokinetics
Sponsor: Pfizer
Start date: 2020-07-03; Completion date: 2022-05-04
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to characterize the effect of kidney impairment on the blood concentrations of PF-06700841 and its major metabolite. Findings from this study will be used to develop dosing recommendations so that the dose and/or dosing interval may be adjusted appropriately in the presence of kidney disease.

Detailed description:
This is a Phase 1 non-randomized, open-label, parallel cohort, multi-site study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-06700841 after a single oral dose of 30 mg. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately 16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted with approximately 8 subjects each with moderate and mild renal impairment. The total duration of participation from Screening visit to Day 4 will be a maximum of 32 days and from Screening visit to Follow-up/Contact Visit will a maximum of 67 days.

Arms: arm 1: This arm includes participants with severe renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1 arm 2: This arm includes participants with normal renal function who will receive a single oral dose of 30 mg PF-06700841 on Day 1 arm 3: This arm includes participants with moderate renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1 arm 4: This arm includes participants with mild renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1
Interventions: intervention 1: PF-06700841
Intervention descriptions: intervention 1: A single dose of 30 mg PF-06700841 will be administered on Day 1

Protocol documents:
Prot_000.pdf: 
PF-06700841
Protocol B7931048
Final Protocol, 20 November 2019
PFIZER CONFIDENTIAL
Page 1
A PHASE 1, NON-RANDOMIZED, OPEN LABEL, SINGLE DOSE STUDY TO
EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF 
PF-06700841 IN PARTICIPANTS WITH RENAL IMPAIRMENT AND IN 
HEALTHY PARTICIPANTS WITH NORMAL RENAL FUNCTION
Investigational Product Number:
PF-06700841
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
N/A
Protocol Number:
B7931048
Phase:
1
Short Title: Renal Impairment Study of PF-06700841
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original protocol
20 November 2019
Not applicable (N/A)


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Final Protocol, 20 November 2019
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
1. PROTOCOL SUMMARY.....................................................................................................8
1.1. Synopsis ....................................................................................................................8
1.2. Schema ......................................................................................................................8
1.3. Schedule of Activities (SoA).....................................................................................9
2. INTRODUCTION ...............................................................................................................13
2.1. Study Rationale .......................................................................................................13
2.2. Background .............................................................................................................13
2.2.1. Nonclinical Pharmacology..........................................................................14
2.2.2. Nonclinical Pharmacokinetics and Metabolism .........................................14
2.2.3. Nonclinical Safety ......................................................................................14
2.2.4. Clinical Overview.......................................................................................15
2.2.4.1. Safety Overview........................................................................15
2.2.4.2. Summary of PF-06700841 Pharmacokinetics in Human..........17
2.3. Benefit/Risk Assessment.........................................................................................18
3. OBJECTIVES AND ENDPOINTS.....................................................................................20
4. STUDY DESIGN.................................................................................................................20
4.1. Overall Design.........................................................................................................20
4.2. Scientific Rationale for Study Design.....................................................................25
4.3. Justification for Dose ..............................................................................................26
4.4. End of Study Definition ..........................................................................................26
5. STUDY POPULATION......................................................................................................26
5.1. Inclusion Criteria.....................................................................................................27
5.1.1. All Participants ...........................................................................................27
5.1.2. Additional Inclusion Criteria for Healthy Participants with Normal 
Renal Function (Cohort 2 only) .......................................................................27
5.1.3. Additional Inclusion Criteria for Participants with Impaired Renal 
Function (Cohort 1 and Cohorts 3 & 4 [if applicable] only)............................28
5.2. Exclusion Criteria....................................................................................................29
5.2.1. All Participants ...........................................................................................29
5.2.2. Additional Exclusion Criteria for Healthy Participants with Normal
Renal Function (Cohort 2, only) ......................................................................32


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5.2.3. Additional Exclusion Criteria for Participants with Impaired Renal 
Function (Cohort 1 and Cohorts 3 & 4 [if applicable] only)............................33
5.3. Lifestyle Considerations..........................................................................................33
5.3.1. Meals and Dietary Restrictions...................................................................33
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................34
5.3.3. Activity .......................................................................................................34
5.3.4. Contraception..............................................................................................34
5.4. Screen Failures ........................................................................................................35
6. STUDY INTERVENTION..................................................................................................35
6.1. Study Interventions Administered...........................................................................35
6.1.1. Administration............................................................................................35
6.2. Preparation/Handling/Storage/Accountability ........................................................36
6.2.1. Preparation and Dispensing........................................................................37
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................37
6.3.1. Allocation to Investigational Product .........................................................37
6.4. Study Intervention Compliance...............................................................................37
6.5. Concomitant Therapy..............................................................................................37
6.5.1. Participants with Healthy Renal Function (Cohort 2 Only) .......................38
6.5.2. Participants with Impaired Renal Function (Cohort 1 and Cohorts 3
& 4 [if applicable])...........................................................................................38
6.6. Dose Modification...................................................................................................38
6.7. Intervention After the End of the Study..................................................................38
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................39
7.1. Discontinuation of Study Intervention ....................................................................39
7.2. Participant Discontinuation/Withdrawal From the Study.......................................39
7.3. Lost to Follow-up....................................................................................................40
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................40
8.1. Efficacy Assessments..............................................................................................41
8.2. Safety Assessments .................................................................................................42
8.2.1. Physical Examinations................................................................................42
8.2.2. Vital Signs ..................................................................................................42
8.2.2.1. Temperature ..............................................................................42


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8.2.3. Electrocardiograms.....................................................................................43
8.2.4. Clinical Safety Laboratory Assessments ....................................................44
8.2.5. Pregnancy Testing ......................................................................................44
8.3. Adverse Events and Serious Adverse Events..........................................................45
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......45
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................45
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................46
8.3.2. Method of Detecting AEs and SAEs ..........................................................46
8.3.3. Follow-up of AEs and SAEs.......................................................................46
8.3.4. Regulatory Reporting Requirements for SAEs...........................................46
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................47
8.3.5.1. Exposure During Pregnancy......................................................47
8.3.5.2. Exposure During Breastfeeding ................................................47
8.3.5.3. Occupational Exposure .............................................................47
8.3.6. Medication Errors .......................................................................................47
8.4. Treatment of Overdose............................................................................................48
8.5. Pharmacokinetics ....................................................................................................49
8.5.1. Plasma for Analysis of PF-06700841 and M1............................................49
8.5.2. Urine for Analysis of PF-06700841 and M1 ..............................................50
8.6. Pharmacodynamics..................................................................................................50
8.7. Genetics...................................................................................................................50
8.7.1. Specified Genetics ......................................................................................50
8.8. Biomarkers ..............................................................................................................51
8.9. Health Economics ...................................................................................................51
9. STATISTICAL CONSIDERATIONS ................................................................................51
9.1. Statistical Hypotheses .............................................................................................51
9.2. Sample Size Determination.....................................................................................51
9.3. Populations for Analysis .........................................................................................52
9.4. Statistical Analyses .................................................................................................52
9.4.1. Efficacy Analyses .......................................................................................53
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9.4.2. Safety Analyses ..........................................................................................53
9.4.2.1. Electrocardiogram Analyses......................................................54
9.4.3.1. Pharmacokinetic Analyses ........................................................54
9.5. Interim Analyses .....................................................................................................55
9.5.1. Data Monitoring Committee.......................................................................56
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................57
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............57
10.1.1. Regulatory and Ethical Considerations ....................................................57
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................57
10.1.2. Financial Disclosure .................................................................................58
10.1.3. Informed Consent Process ........................................................................58
10.1.4. Data Protection .........................................................................................59
10.1.5. Dissemination of Clinical Study Data ......................................................59
10.1.6. Data Quality Assurance ............................................................................60
10.1.7. Source Documents....................................................................................62
10.1.8. Study and Site Closure..............................................................................62
10.1.9. Publication Policy.....................................................................................62
10.1.10. Sponsor’s Qualified Medical Personnel .................................................63
10.2. Appendix 2: Clinical Laboratory Tests .................................................................64
10.2.1. Hepatitis B and C Testing Algorithm and Full Eligibility Criteria ..........65
10.2.2. Tuberculosis Testing.................................................................................66
10.2.2.1. Purified Protein Derivative Test..............................................66
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................67
10.3.1. Definition of AE .......................................................................................67
10.3.2. Definition of SAE.....................................................................................68
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................69
10.3.4. Reporting of SAEs....................................................................................72
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information................................................................................................................74
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10.4.1. Male Participant Reproductive Inclusion Criteria....................................74
10.4.2. Female Participant Reproductive Inclusion Criteria.................................74
10.4.3. Woman of Childbearing Potential (WOCBP) ..........................................75
10.4.4. Contraception Methods.............................................................................76
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........80
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................82
10.8. Appendix 8: Abbreviations ...................................................................................84
11. REFERENCES ..................................................................................................................88
LIST OF TABLES
Table 1.
Renal Function Categories by eGFR Ranges ...........................................21
Table 2.
Criteria to Establish Stable Renal Function..............................................24
Table 3.
Plasma PK Parameters..............................................................................55
Table 4.
Urine PK Parameters ................................................................................55
Table 5.
Protocol-Required Safety Laboratory Assessments .................................64
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1. PROTOCOL SUMMARY
1.1. Synopsis
Not Applicable.
1.2. Schema
Not Applicable.


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1.3. Schedule of Activities (SoA)
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 Identifiera
Screeningb
Day -1b
Day 1
Day 2
Day 3
Day 4
Follow-up 
Contact
Early Termination/
Discontinuation
(DC)
Day -28 to Day -2
Days Relative to Day 1
S1
S2
28-35 Daysc
Informed consent
X
Admission to CRU
X
Confinement to CRU
X



X
Inclusion/exclusion criteria
X
X
Medical history 
X
X
Demographyd
X
Physical examinatione
X
X
X
Height and weight assessmentf
X
X
X
Xg
Safety laboratory tests (blood and 
urine)h
X
Xi
X
X
Xg
X
eGFR assessmentj
X
X
X
Xg
QuantiFERON®-TB Gold Test or 
PPD skin testk
X
Illegal drug/tobacco/alcohol use
X
X
Urine alcohol test or alcohol 
breath test
X
X
Urine or serum pregnancy test 
(WOCBP only)
X
X
X
X
Contraception checkl
X
X
X
X
X
Serum FSH in post-menopausal 
females amenorrheic ≥12 months 
and under 60 years of age
X
Urine drug screen
X
X
Single supine 12-Lead ECG
X
Xm
X
X


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Visit Identifiera
Screeningb
Day -1b
Day 1
Day 2
Day 3
Day 4
Follow-up 
Contact
Early Termination/
Discontinuation
(DC)
Day -28 to Day -2
Days Relative to Day 1
S1
S2
28-35 Daysc
Vital signs (supine BP, pulse 
rate) and temperature
X
X
X
X
HIV, HBsAg, HBcAb, HCVAb 
testingn
X
Investigational product
administration
X
Plasma PK for PF-06700841 and 
M1
X
X
X
X
X
Urine PK for PF-06700841 and 
M1
X
X
X
X
 
Prior/concomitant treatments
X
X
X
→
→
→
X
X
X
CRU discharge 
X
Serious and nonserious adverse 
event monitoring
X
X
X
→
→
→
X
X
X
Abbreviations: →= ongoing/continuous event; BP = blood pressure; DC = discontinuation; eGFR = estimated glomerular filtration rate; HBcAb = hepatitis B core antibody; 
HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C antibody; HIV = human immunodeficiency virus; CRU = clinical research unit; ECG = electrocardiogram; 
FSH = follicle-stimulating hormone; PK = pharmacokinetic; PPD = purified protein derivative; QFT-G = QuantiFERON®-TB Gold; S1= Screening Visit 1; S2= Screening 
Visit 2; WOCBP = women of childbearing potential; M1 = a major metabolite of PF-06700841.
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Visit Identifiera
Screeningb
Day -1b
Day 1
Day 2
Day 3
Day 4
Follow-up 
Contact
Early Termination/
Discontinuation
(DC)
Day -28 to Day -2
Days Relative to Day 1
S1
S2
28-35 Daysc
a.
Day relative to start of study treatment (Day 1).
b.
Screening will consist of 2 CRU outpatient visits (Screening Visits 1 and 2) between 3 to 14 days apart, with the 1st screening visit occurring within 28 days 
prior to investigational product administration (Day 1).  The 2nd screening visit is only to demonstrate stable renal function with difference between eGFRs 
at Screening visit 1 (S1) and Screening visit 2 (S2) required to be ≤25% of the value obtained at S1. If participant meets all screening criteria at S2 visit, and 
Day -1 visit can be performed immediately, the participant may be admitted to the unit at conclusion of S2 visit.  Other screening procedures completed 
during the first visit (S1) do not need to be repeated.  See Section 4.1 for outpatient visit screening schedule.
c.
Contact may occur via telephone contact and must occur 28 to 35 days from administration of the investigational product or from the time of early 
termination/discontinuation. If participant demonstrates an increase of >25% in serum creatinine from Day -1 to Day of discharge, he or she will be asked 
for a follow-up visit to collect eGFR.
d.
Demographics will include race, age and gender.
e.
Complete physical examination at Day -1, Day 4, and early termination.  Limited physical examination at any time point as deemed necessary by the 
investigator.
f.
Height to be obtained at S1 only, weight to be obtained at S1, S2 and Days -1.
g.
Only when the participant demonstrates an increase of >25% in serum creatinine from Day -1 to Day of discharge. Only serum creatinine and weight 
information will be collected for eGFR assessment. 
h.
Safety laboratory assessments include chemistry, hematology and urinalysis (and microscopy, if needed) and will be performed at S1, on Day -1, Day 4 and 
early termination day.  All the assessments must be collected following at least a 4 hour fast.  
i.
Serum creatinine only will be assessed on S2 for eGFR assessment.
j.
To confirm eligibility, participants must have stable renal function defined as ≤25% difference for eGFR values at S2 compared to the value at S1.  The 
average of the 2 screening eGFR values will be used for participant stratification and group assignment (provided stable renal function is still demonstrated).
If the renal function stability criterion is met but the renal function classification category changes between S1 eGFR and the average of the S1 and 
S2 eGFRs, the eGFR measurement at Day -1 will also be used to determine the appropriate group classification category using an average of all 3 eGFR 
values, to determine whether the participant will be eligible for enrollment. The Day -1 eGFR value will be used for PK analysis.  The eGFR determination 
will utilize the 4-variable MDRD equation. A follow-up eGFR will be collected at Day 28 (with window of +3 days to allow for holidays) for any participant
who demonstrates an increase of >25% in serum creatinine from Day -1 to Day of discharge.
k.
If QFT-G test cannot be performed, or if results are indeterminate, participants may be screened using PPD Tuberculin Test (Mantoux method), with 
approval of medical monitor.
l.
Confirmation of appropriate use only.
m.
Triplicate 12-lead ECG will be performed at 0 hr pre-dose on Day 1.  Single 12-lead ECG will be collected at 1, 3, and 6 hr post-dose on Day 1.  
n.
HBsAb will be performed as reflex testing for any participant who is HBsAg negative and HBcAb positive (Section 10.2.1).  HCV RNA will be performed 
as reflex testing for any participant who is HCV Ab positive (Section 10.2.1).
 
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Pharmacokinetic Sampling Schema
Visit Identifier 
Study Day
1
2
3
4
Hours Before/After Dose
0a
0.5
1
2
3
4
6
8
10
12
24
36
48
72
Investigational product
administration
X
PK blood samplingb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK urine collectionc
X









X

X
X
Abbreviation: = ongoing/continuous event, PK = pharmacokinetic.  
a.
Predose sample collection.
b.
Blood samples are to be collected for plasma PK assessment of both PF-06700841 and M1.
c.
Urine collections during intervals of ≤24, >24 and ≤48, and >48 and ≤72 hours after dosing on Day 1. During the subsequent designated urine collection intervals ([0-24], 
[24-48], and [48-72] hours post dose), participants will void ALL urine produced during the designated collection interval, including a forced void at the end of the collection 
interval, directly into pre-weighed urine collection container. Urine samples will be analyzed using a validated analytical method in compliance with Pfizer SOPs, only if it is 
determined by the study team that there is a need to do so, based on review of PF-06700841 and M1 plasma PK results.


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2. INTRODUCTION
PF-06700841 is a potent tyrosine kinase 2 (TYK2)/Janus kinase (JAK) 1 inhibitior that is 
currently being developed for the treatment of patients with inflammatory diseases, including 
systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), psoriasis (PsO), alopecia 
areata (AA), vitiligo, inflammatory bowel disease (IBD), hidradenitis suppurativa (HS) and 
atopic dermatitis (AD).
2.1. Study Rationale 
In vitro and in vivo metabolite profiling suggested that the primary clearance mechanism for 
PF-06700841 was cytochrome P450 (CYP450) mediated oxidation. The contribution of 
individual CYP450 involved in the metabolism of PF-06700841 (1 µM) was assessed in a 
preliminary reaction phenotyping study using a human hepatocyte relay method. Greater 
than 88% of the PF-06700841 metabolism observed was attributed to CYP450 with CYP3A4 
identified as the major contributor (fraction metabolized [fm] = 0.62). In the first in human 
study, B7981001, urinary recovery of PF-06700841 was low, with <16% of the dose 
recovered unchanged in urine across all doses (geometric mean Aeτ% of 8.9% to 15.5%), 
indicating that the renal pathway plays a minimal role in PF-06700841 excretion.  
Evidence suggests that the pharmacokinetics (PK) of drugs that are not only excreted by the 
kidney can be affected by renal impairment through inhibition of pathways of hepatic and gut 
drug metabolism and transport.1  Consequently, recent European Medicines Agency (EMA)
guidelines suggest that renal impairment studies be conducted in patients with decreased 
renal function for nearly all small molecules, even if the drug or its active metabolite is not 
primarily eliminated by the kidneys.2 The revised Food and Drug Administration (FDA) 
Draft Guidance on renal impairment studies also recommends that a PK study be conducted 
in participants with renal impairment when the drug is likely to be used in patients with 
impaired renal function.1
PF-06700841 is intended for chronic use in patients, some of whom may have some degree 
of impaired renal function. Therefore, the purpose of this study is to characterize the effect 
of renal impairment on the plasma PK of PF-06700841.  Findings from this study will be 
used to develop dosing recommendations so that the dose and/or dosing interval may be 
adjusted appropriately in the presence of renal disease.
2.2. Background
PF-06700841 is a dual TYK2/JAK1 inhibitor with a high selectivity profile over other human
kinases. The clinical efficacy of JAK1 inhibition with tofacitinib has been established in PsA, 
PsO and in IBD.3,4,5 PF-06700841 targets the JAK1-dependent pathways, and in addition, 
inhibiting TYK2 is expected to lower interleukin (IL)-12, IL-23 and Type I interferon (IFN) 
signaling to a greater degree than JAK1 inhibition alone.  Accumulating evidence indicates 
that the IL-23/T help 17 (Th17) pathway plays an important role in the pathology of PsO, 
PsA, AA and IBD. Inhibition of both JAK1 and TYK2 is expected to provide greater 
therapeutic benefit in the treatment of plaque PsO, PsA, AA, AD, SLE, HS, vitiligo and IBD. 
In Study B7931001, PsO participants receiving active treatment with PF-06700841 (30 mg or 
100 mg once daily [QD] for 28 days) had clinically meaningful decreases in disease activity 


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as measured by Psoriasis Area and Severity Index (PASI; a validated PsO clinical disease 
activity metric accepted by regulatory agencies).  Preliminary safety, efficacy, and 
pharmacodynamics results from Study B7931001 support further development of 
PF-06700841 in plaque PsO, PsA (based on the PsO data) and possibly IBD. A Phase 2 
study B7931004 to assess the safety and efficacy of several dose levels of PF-06700841 in 
participants with moderate-to-severe chronic plaque PsO was completed.  PF-06700841 is 
currently under assessment in 4 ongoing Phase 2 studies in AA (B7931005), ulcerative colitis
(UC) (B7981005), Crohn’s Disease (CD) (B7981007) and SLE (B7931028). Ongoing and 
future studies with PF-06700841 explore doses up to 60 mg given QD.
2.2.1. Nonclinical Pharmacology
Details of the nonclinical pharmacology of PF-06700841 can be found in the current 
Investigator Brochure (IB).
2.2.2. Nonclinical Pharmacokinetics and Metabolism
Hepatic CYP450 enzymes were implicated in the clearance of PF-06700841 in initial parent 
drug conversion studies in rat, monkey, and/or human liver microsomes and hepatocytes.
There was no evidence of aldehyde oxidase-mediated PF-06700841 metabolism in a human 
cytosol screen.  The contribution of individual CYP450 involved in the metabolism of 
PF-06700841 (1 µM) was assessed in a preliminary reaction phenotyping study using a 
human hepatocyte relay method. Greater than 88% of the PF-06700841 metabolism 
observed was attributed to CYP450 with CYP3A4 identified as the major contributor 
(fm = 0.62). Human Absorption, Distribution, Metabolism and Elimination (ADME) study 
(B7931014) is ongoing to definitively assess elimination pathways and metabolic profiles.
Additional information of the nonclinical PK and metabolism of PF-06700841 is available in 
the current IB.
2.2.3. Nonclinical Safety
No adverse findings were observed in oral repeat-dose toxicity studies with PF-06700841 in 
rats and monkeys up to 6 and 9 months in duration, respectively.  PF-06700841-related, 
non-adverse, target organs identified include the immune and hematolymphopoietic systems 
(thymus, spleen, lymph nodes, and bone marrow), cardiovascular system (blood pressure, 
heart rate, corrected QT wave interval [QTc]), gastrointestinal tract (body weight and weight 
gain effects), and adrenal gland (vacuolation).  The findings in the thymus, spleen, lymph 
nodes, and bone marrow are consistent with the pharmacological activity of PF-06700841.  
The no-observed-adverse-effect level (NOAELs) in the 6-and 9-month toxicity studies were 
45 mg/kg/day in rats (unbound Cmax of 8280 ng/mL and area under the curve from time 0 to
24 hours [AUC24] of 69,700 ng•h/mL) and 20 mg/kg/day in monkeys (unbound maximum 
plasma concentration [Cmax] of 2260 ng/mL and AUC24 of 10,700 ng•h/mL).  Adverse 
findings in the central nervous system (decreased activity, mortality, prostration, 
convulsions) were observed at high systemic exposures in pregnant, but not in non-pregnant 
rabbits.


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In oral embryo-fetal development studies in rats and rabbits, adverse PF-06700841-related 
developmental effects occurred (lower embryo-fetal viability and mean fetal body weights, 
fetal skeletal malformations, external malformations).  The developmental NOAEL in rabbits 
was 1 mg/kg/day (unbound Cmax of 174 ng/mL and AUC24 of 608 ng•h/mL).
The developmental NOAEL in rats was not established and is <2 mg/kg/day (unbound Cmax
of 482 ng/mL and AUC24 of 2240 ng•h/mL), the lowest dose tested.  No effects on female 
reproductive organs, as assessed by histopathologic examination, were noted in either the rat 
or monkey repeat-dose toxicity studies.  PF-06700841 is not mutagenic in bacterial reverse 
mutation assays.  Although PF-06700841 was positive for micronuclei formation in vitro 
(through an aneugenic mechanism), it did not induce micronuclei in vivo in rats at
55 mg/kg/day (unbound Cmax = 7730 ng/mL and AUC24 = 88,300 ng•h/mL), the highest dose 
tested in the 1-month oral toxicity study.
Further details of the nonclinical safety program are provided in the current IB.
2.2.4. Clinical Overview
The sponsor’s clinical development program for PF-06700841 consists of 3 completed 
Phase 1 studies in healthy participants and PsO participants (B7931001, B7931009 and 
B7931010), 1 complete Phase 2 study in PsO (B7931004), and is currently under assessment 
in 6 ongoing Phase 2 studies in AA (B7931005), UC (B7981005), CD (B7981007) and SLE
(B7931028), vitiligo (B7981019), PsA (B7931030), and 1 planned Phase 2 study in HS 
(C2501007).  In addition, 2 Phase 1 studies in healthy participants are clinically complete and
preparation of the clinical reports including a study to assess effect of PF-06700841 on QTc 
interval (B7931019) and a human ADME study using 14C microtracer (B7931014). A drug 
interaction study with a potent CYP3A4 inhibitor, itraconazole (B7931033) is ongoing.  The 
studies described above have all used oral administration of PF-06700841.  The topical 
development program consists of 1 completed Phase 1 study (B7931029), and 2 ongoing 
Phase 2 studies in AD (B7931022) and PsO (B7931023). 
Included in this Clinical Overview are summaries of the results from only the clinically 
completed Phase 1 studies, B7931001, B7931009, B7931010, B7931014 and B7931019,
Phase 2 study in PsO, B7931004 and ongoing Phase 2 study in AA with an interim analysis 
study result (B7931005).
2.2.4.1. Safety Overview
Overall, PF-06700841 was generally well-tolerated in healthy volunteers (B7931001,
B7931009, B7931010, B7931014, and B7931019); PsO (B7931001 and B7931004) and AA
participants (B7931005). There were no clinical meaningful findings in vital signs, suicidal 
behavior or ideation, or potential Hy’s Law cases reported during these studies.
Refer to the IB for more details on the clinical safety information with PF-06700841.


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2.2.4.1.1. Phase 1 Studies
In first-in-human (FIH) study B7931001, the most commonly reported all causality 
treatment-emergent adverse events (TEAEs) across active participants in both healthy 
volunteers and PsO participants were blood creatinine increased, leading to 5 withdrawals in 
the study. Participants in the multiple ascending dose [MAD] and PsO periods that had 
increased serum creatinine (SCr) ≥0.3 mg/dL did not demonstrate significant changes in S 
Cystatin-C based estimated glomerular filtration rate (eGFR), suggesting that the change in 
creatinine - based eGFR might be caused by changes in renal handling of creatinine, rather 
than by alteration of renal function. The most frequently reported laboratory abnormalities 
were increases in low-density lipoprotein (LDL), serum creatinine, and decreases in 
neutrophil counts in participants receiving PF-06700841 during single ascending dose 
[SAD]/MAD and psoriatic period. Neutrophil count decreased (reported in 4 participants 
during the MAD period), leading to 3 withdrawals in the study.
In B7931009, B7931010 and B7931014 studies, oral administration of PF-06700841 was 
well-tolerated in healthy participants investigated in the study. There were no deaths, serious 
adverse events (SAEs), severe adverse events (AEs), discontinuations due to AEs, or dose 
reductions or temporary discontinuations due to AEs during this study. There were no 
clinically significant findings observed in laboratory parameters, vital signs, 
electrocardiogram (ECG) parameters.
A formal through QT study (B7931019) suggested PF-06700841 has a small effect on QT 
prolongation. Following a single dose of 200 mg PF-06700841, the maximum
placebo-corrected QT interval corrected using Fridericia’s correction factor (QTcF) change 
from baseline was observed at 3 hours post-dose with mean of 14.6 ms and 90% confidence 
interval (CI) of (12.4, 16.8 ms). As expected, the maximum mean change in QTcF observed 
following administration of 400 mg moxifloxacin was 13.8 ms (90% CI:11.6, 16.0 ms). 
Despite QTc effect observed after single doses of PF-06700841 200 mg and moxifloxacin 
400 mg, there were no clinically significant findings in ECG categorical analyses in that QTc 
change from baseline >60 msec or QTc absolute value >500 msec was not observed. Based 
on the concentration-QTcF analysis, the primary analysis defined in this study, the estimated 
QTcF increase at predicted Cmax of PF-06700841 60 mg QD, the highest clinical dose used in 
ongoing Phase 2 studies, is approximately 8.8 ms with the upper bound of 90% CI (10.2 ms) 
slightly exceeding 10 ms threshold.
2.2.4.1.2. Phase 2 Studies 
A total of 189 PsO participants out of 212 enrolled in B7931004 were exposed to at least 
1 dose of PF-06700841 during the study.  The proportion of participants with all-causality
TEAEs was comparable across all treatment arms but numerically higher in the active 
treatment arms (64.0% to 76.7%) than the placebo group (56.5%).  The majority of 
participants in all treatment arms experienced mild or moderate all-causality TEAEs, and 
only 5.2% experienced severe all-causality TEAEs.


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Overall, there were no dose-dependent increases in the all-causality TEAEs.  Most TEAEs in 
the Infection and Infestation class were mild to moderate except 1 participant who had 
2 serious infections after taking a single dose of 60 mg PF-06700841 on Day 1.  One 
(1) participant in the 30 mg QD to 100 mg once a week (QW) group had squamous cell 
carcinoma of skin reported on Day 2 of treatment.  One (1) participant in the 30 to 10 mg 
group was confirmed to be pregnant after being in the study for 42 days and was 
discontinued from the study with obstetrical ultrasound demonstrating fetal cleft lip.
Decreased reticulocytes, hemoglobin, and neutrophils were observed in the participants on
active treatment during 4-week induction phase and returned toward baseline level during 
8-week maintenance phase.  Increases in serum creatinine from baseline were observed in all 
active treatment arms with no association of change in cystatin C based renal function 
measurement.  Other commonly reported laboratory abnormalities were elevation of LDL 
with no clinical meaningful changes in LDL/high density lipoprotein (HDL) ratio.  Creatine 
kinase (CK) levels >10 × upper limit of normal (ULN) were observed in two participants 
without adverse event (AE).  One moderate AE of CK-myoglobin increase was reported by 
one participant in the 30 to 10 mg QD group during the induction period, which was 
considered to be related to the investigational product by the investigator.  No participant was 
discontinued from the study due to CK elevation.
In Study B7931005, 47 AA participants were exposed to at least 1 dose of PF-06700841.  
The most commonly reported TEAEs in the active treatment arm was in the Infections and 
Infestations system organ class (SOC) (51.1% in the investigational product vs 40.4% in the 
placebo).  Other TEAEs were Gastrointestinal Disorders (23.4% in the investigational 
product vs 25.5% in the placebo).  Most of those TEAEs were mild.  There were 2
participants receiving PF-06700841 that experienced rhabdomyolysis after strenuously 
exercising during the study, which were not considered to be related to the investigational 
product by investigator assessment.  Three participants experienced mild decreases in 
neutrophils, one participant had a mild reduction in platelets, and one participant a mild 
reduction in lymphocytes.
2.2.4.2. Summary of PF-06700841 Pharmacokinetics in Human
In Study B7931001, following single oral doses of 1 mg to 200 mg under fasted conditions, 
PF-06700841 was absorbed rapidly with median time to maximum concentration (Tmax) of 
1 hour or less.  Mean terminal half-life (t½) ranged from 3.8 to 7.5 hours.  In general, both the 
area under the concentration-time curve from time 0 to infinity (AUCinf) and Cmax appeared 
to increase proportionally with dose from 1 mg to 100 mg.  Increases from 100 mg to 200 mg 
appear more than dose proportional, especially for AUCinf.
On Day 10 of multiple dose administration, PF-06700841 was absorbed rapidly with median 
Tmax of 1 to 1.5 hours or less across the entire range of doses, from a total daily dose of 
10 mg up to 175 mg.  Following attainment of Cmax, the disposition of PF-06700841 was 
similar with that observed following single dose administration.  Mean t½ ranged from 4.9 to 
10.7 hours.  Both area under the concentration-time curve from time 0 to time (AUC) and 
Cmax generally appeared to increase proportionally with dose from 10 mg to 100 mg QD, 
with a trend towards greater than proportional increase from 100 mg to 175 mg QD.  


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Accumulations, following once daily dosing, ranged from 1.1 to 1.4 for AUCt and 0.8 to 
1.1 for Cmax.  The urinary recovery of unchanged (Ae%) PF-06700841 on Day 10 across all 
doses ranged from 8.9% to 15.5%.  Following multiple dose administration of PF-06700841 
to participants with PsO for 28-days, the overall exposure observed was comparable to that in 
healthy participants at same dose level.
The relative bioavailability of a solid dose formulation of PF-06700841 relative to a solution 
and the food effect on the solid dosage formulation was also evaluated.  Following single oral 
100 mg doses under fasting conditions, median Tmax was 0.5 hours for the tablet formulation 
and 1.0 hours for the solution.  The ratios of adjusted geometric means between tablet versus 
solution formulation were 96.2% for AUCinf and 94.3% for Cmax.  When the tablet was 
administered following a high fat meal, Tmax was delayed with median of 4.0 hours and the 
AUCinf and Cmax were 82.3% and 64.3%, respectively of those observed when tablets were 
given fasted.
In Study B7931009, higher exposure in Japanese participants (n=6) observed compared to 
that in non-Japanese participants from B7931001 study: the mean steady state Cmax were 
1114 (14%) vs 734.1 (29%) ng/mL and steady state mean AUC24 were 9888 (33%) vs 
6089 (38%) ng•h/mL for Japanese participants and non-Japanese participants respectively 
after multiple doses of 100 mg QD.
In the recently clinically completed ADME study B7931014, the preliminary metabolite 
profiling analysis identified a single major metabolite M1 (PF-06802530). PF-06802530 is 
primarily formed via CYP3A-mediated hydroxylation of PF-06700841 and mainly 
eliminated via renal excretion.
B7931004 study was recently completed.  In this study, PK samples were collected at 
pre-dose and/or 0.5 hours post-dose at each visit over 12-week treatment. Post-dose samples 
were also collected up to 4 hours at Weeks 4 and 12.  Plasma concentrations of PF-06700841 
observed were as expected based on PK in PsO participants.
2.3. Benefit/Risk Assessment
PF-06700841 is not expected to provide any clinical benefit to healthy participants or 
participants with renal impairment in this study.  This study is designed primarily to 
characterize the effect of renal impairment on the plasma PK of a single dose of 
PF-06700841.  The data from this study are expected to provide the basis for development of 
dosing recommendations for target patient populations who may have renal impairment.  
Based on the data in Phase 1 program, the clinical safety profile of PF-06700841 appears to
be acceptable at dosages up to 200 mg single dose and 175 mg repeated daily doses 
administered orally.  Based on the clinical experience with PF-06700841 and/or other JAK 
inhibitors (eg, Xeljanz® [tofacitinib], Jakafi® [ruxolitinib], baricitinib, filgotinib and 
upadacitinib), anticipated risks with PF-06700841 include: (1) an increase in susceptibility to 
infection, (2) viral reactivation, (3) malignancy and lymphoproliferative disorders, 
(4) alterations in laboratory parameters, including: decreased neutrophil counts, decreased 
lymphocyte counts, decreased hemoglobin level, decreased platelet counts, alterations in the 


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hepatic transaminases and serum creatinine.  There was one AE of herpes zoster infection in 
a PsO participant treated with 100 mg PF-06700841 for 4 weeks.  Laboratory changes can be 
managed by monitoring criteria as well as adjustment of the inclusion/exclusion criteria.
Based on in vitro data, moderate and strong CYP3A inhibitors or inducers, strong 
P-glycoprotein (P-gp) inhibitors, P-gp substrates and substrates of organic cation transport
2 (OCT2)/multidrug toxin extrusion protein (MATE) with a narrow therapeutic index, will be 
prohibited during PF-06700841 treatment periods in ongoing Phase 2 studies to minimize 
any potential significant drug interaction.  Detailed information about in vitro assessments on 
drug metabolism, enzyme phenotype and drug-drug interaction can be found in the IB.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of PF-06700841 may be found in the IB, which is the single 
reference safety document (SRSD) for this study.


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3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary:
Primary:
•
Part 1: To evaluate the effect of severe renal 
impairment on the PK of PF-06700841 and
M1, a major metabolite of PF-06700841,
following single oral dose administration.
•
Part 2 (if applicable): To evaluate the effect of 
moderate and mild renal impairment on the 
PK of PF-06700841 and M1 following single
oral dose administration.
•
Plasma PF-06700841 and M1 PK parameters: 
Cmax and AUCinf.
Secondary:
Secondary:
•
To evaluate the safety and tolerability of 
single oral dose of PF-06700841 in 
participants with renal impairment and in 
healthy participants with normal renal 
function.
•
Safety: treatment-emergent adverse events, 
clinical laboratory tests, vital signs, physical 
examination and ECGs.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1, non-randomized, open-label, single-dose, parallel-cohort study to 
investigate the effect of renal impairment on the plasma PK, safety and tolerability of 
PF-06700841 after single oral dose of 30 mg in approximately 2 clinical research units 
(CRU).  A staged approach, as outlined in detail below, will be followed in the study.
Participants will be selected and categorized into normal renal function or renal impairment 
groups based on their estimated glomerular filtration rate (eGFR) as shown in Table 1.
CCI


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Table 1.
Renal Function Categories by eGFR Ranges
Cohort
Renal Impairmenta
Estimated eGFRb (mL/min)
Number of Participants
1
Severe Renal Impairment
<30 and not requiring dialysis
8
2
None (Normal)
≥90
8
3
Moderate Renal Impairment
≥30 to <60
8
4
Mild Renal Impairment
60 – 89
8
a.
Stages of renal impairment are based on Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical 
Practice Guidelines for Chronic Kidney Disease (CKD).1
b.
Estimate of eGFR based on Modification of Diet in Renal Disease (MDRD) formula.  The average of the 
2 screening eGFR value will be used for group assignment.

Step 1: eGFR (mL/min/1.73m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female) 
× (1.212 if African American) where Scr, std denotes serum creatinine measured with a standardized 
assay.

Step 2: Convert the MDRD-derived, body surface area (BSA)-adjusted eGFR obtained above to 
absolute eGFR (mL/min) for eligibility assessment using the following equation: 
eGFR (mL/min) = eGFR (mL/min/1.73m2) × participant’s BSA where BSA is calculated as 
BSA= (Weight0.425 × Height0.725) × 0.007184.
Part 1: A total of approximately 16 participants will be enrolled in Part 1; approximately 
8 participants with severe renal impairment (Cohort 1) and approximately 8 with normal 
renal function (Cohort 2) to ensure at least 6 evaluable participants in each group. 
Participants from the severe renal impairment group will be recruited first. The 
demographics will be pooled across study sites to determine an average value for age and 
weight in the severe impairment group. Subsequently, the healthy participants will be 
recruited later such that each participant’s age is within ±10 years and weight is within 
±15 kg of the mean of severe renal impairment group. An attempt will be made to maintain a
similar male/female ratio composition between groups. Care will be taken when recruiting 
the healthy participants such that the entire group is not of substantially different age or of 
substantially different body weight than the severely renally impaired participants.  Approval 
from the sponsor must be obtained before proceeding with dosing healthy participants with 
normal renal function.
If there are participants who withdraw or discontinue treatment from the normal or severe 
renal impairment groups and who are considered to be non-evaluable with respect to the 
primary PK objective, additional participants can be enrolled at the discretion of the sponsor.
Criteria to proceed to Part 2: After statistical evaluation of results from Part 1 (see
Section 9.4), Part 2 will be conducted if the point estimate of PF-06700841 or M1 area under 
the concentration-time curve from time 0 to infinity (AUCinf) geometric mean ratio (GMR) 
for the severe renal impairment group (compared to the normal group as control) is ≥1.5.  If 
this criterion is not met, the study will stop after Part 1.
Part 2: Based on whether the decision criterion to proceed to Part 2 is met, approximately 
8 participants each with moderate (Cohort 3) and mild (Cohort 4) renal impairment will be 
enrolled to ensure at least 6 evaluable participants in each group. As in Part 1, renal 
impairment classification will be based on eGFR. Healthy participants will not be enrolled in 


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Part 2. Healthy participants from Part 1 will be used as the control group for the moderate 
and mild impairment participants. 
When recruiting the Part 2 participants, attempts to match the entire group to the participants 
in Part 1 with respect to age, gender and body weight will be made. Other demographics, 
such as race and ethnicity, may be considered for matching the Part 1 and Part 2 populations
when possible. Statistical considerations to account for any differences in demographics are 
detailed in Section 9.4.
As in Part 1, if there are participants who withdraw or discontinue treatment from the 
moderate or mild impairment group and who are considered to be non-evaluable with respect 
to the primary PK objective, additional participants can be enrolled at the discretion of the 
sponsor. 
For both Parts 1 and 2: All participants in both normal and renal impairment groups will 
provide informed consent and undergo Screening evaluations to determine their eligibility.  
Participant screening for participation in this study will consist of 2 CRU outpatient visits not 
more than 14 days apart (but at least 3 days apart), with the 1st screening visit occurring 
within 28 days prior to administration of investigational product.  Each participant will be 
admitted to the research unit on Day -1 (at least 12 hours prior to the dosing of PF-06700841
on Day 1).  An eGFR value for group placement (provided stable renal function is still 
demonstrated) will be obtained by the average of the 2 screening values (using the 
Modification of Diet in Renal Disease [MDRD] equation). If the renal function stability 
criterion is met but the renal function classification category changes between Screening 
Visit 1(S1) eGFR and the average of the S1 and Screening Visit 2 (S2) eGFRs, the eGFR 
measurement at Day -1 will also be used to determine the appropriate group classification 
category using an average of all 3 eGFR values, to determine whether the participant will be 
eligible for enrollment.
Eligible participants will be admitted to the CRU on Day -1 and will be confined in the CRU 
until Day 4. If participant meets all screening criteria at S2 visit, and Day -1 visit can be 
performed immediately, the participant may be admitted to the unit at conclusion of S2 visit.  
On the morning of Day 1, the participants will receive a 30 mg single dose of PF-06700841
after a fast of at least 10 hours. No food will be allowed for at least 4 hours post-dose. Serial 
blood and urine samples at specified intervals (as per Schedule of Activities) will be 
collected for 72 hours post-dose for plasma and urine PK assessments, prior to discharge 
from the CRU on Day 4. The eGFR value will be determined on Day -1 and will be used in
PK analysis.  
Safety assessments (as specified in the Schedule of Activities) will be performed during S1, 
on Day -1 and prior to dosing on Day 4. Only serum creatinine will be additionally assessed 
on S2 for eGFR estimation. Physical examinations, vital sign measurements, and clinical 
laboratory tests will be conducted and AEs will be monitored as per Schedule of Activities to 
assess safety.  The total participation time (ie, CRU confinement time for study procedures) 
for each participant in this study is approximately 4 nights/5 days (excluding screening &


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Follow-Up contact).  Participants will have a follow-up phone contact 28-35 days after last 
IP administration to assess for AEs. If participant demonstrates an increase of >25% in SCr
from Day -1 to Day of discharge, he or she will be asked for a follow-up visit to collect 
eGFR.
All procedures and their timelines follow the Schedule of Activities.  
Calculation of eGFR:
The following MDRD equation will be used to calculate eGFR (Scr, std denotes serum 
creatinine measured with a standardized assay for serum creatinine):
eGFR (mL/min/1.73m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female) 
× (1.212 if African American)
Note that the value of eGFR, which is directly obtained from the laboratory or calculated 
using the equation above, is generally normalized to an average body size of 1.73 m2 for 
diagnosis, prognosis and treatment of renal disease.  In terms of clearance of renally filtered 
drugs (including secreted drugs), renal elimination capacity is related to absolute glomerular 
filtration rate (GFR) in mL/min. To use the MDRD-derived, body surface area 
(BSA)-adjusted value of eGFR to obtain absolute glomerular filtration rate (GFR) (mL/min)
for renal disease classification or participant assignment into different renal disease groups, 
this value should be multiplied by the individual participant’s BSA (ie, measured 
BSA/1.73 m2). The BSA of an individual can be calculated by the following formula as 
described below:
BSA = (Weight0.425 × Height0.725) × 0.007184
In summary, GFR in mL/min calculated as below will be used for renal impairment group 
placement:  
Step 1: Obtain the MDRD-derived eGFR:

eGFR (mL/min/1.73m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female) 
× (1.212 if African American) where Scr, std denotes serum creatinine measured with a 
standardized assay.
Step 2: Convert the MDRD-derived, BSA-adjusted eGFR obtained above to absolute GFR 
(mL/min) for eligibility assessment using the following equation: 

eGFR (mL/min) = eGFR (mL/min/1.73m2) × participant’s BSA where BSA is 
calculated as BSA = (Weight0.425 × Height0.725) × 0.007184.


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Creatinine clearance (CLCR) will also be estimated from a spot serum creatinine measurement 
using the following Cockcroft-Gault (C-G) equation:
CLCR (mL/min) = (140 – age [years]) × total body weight (kg) × (0.85 for females)
72 × serum creatinine (mg/dL)
Note that eGFR calculated by the MDRD equation will be used for categorization of degrees 
of renal impairment.  Nevertheless, renal function will be estimated using both C-G and 
MDRD equations in this study and dose recommendations will be made using both C-G and 
MDRD equations.
To be enrolled into the study, participant must demonstrate stable renal function, with 
≤25% change based upon screening S1 eGFR and screening S2 eGFR (calculated by the 
MDRD equation). The S2 eGFR assessment should be performed between 3 to 14 days after 
the S1 eGFR assessment. The average of these 2 eGFR values will be used for group 
placement based on the renal function classification category.

If the renal function stability criterion is met and the renal function classification 
category remains the same between S1 eGFR and the average of the S1 and 
S2 eGFRs, participant will be eligible for enrollment.

If the renal function stability criterion is not met, participant will be screen failed.

If the renal function stability criterion is met but the renal function classification 
category changes between S1 eGFR and the average of the S1 and S2 eGFRs, the 
eGFR measurement at Day -1 will also be used to determine the appropriate group 
classification category using an average of all 3 eGFR values, to determine whether 
the participant will be eligible for enrollment.  
In case of screen failure related to eGFR stability and/or change in the renal function 
classification category, participant may be re-screened once after a 30-day period, provided 
that the initial screen failure is not due to an Inclusion/Exclusion criterion that results in 
permanent disqualification from enrollment (eg, medical history).  This can be done only 
with sponsor’s approval.
Please see Table 2 below regarding demonstration of stable renal function:
Table 2.
Criteria to Establish Stable Renal Function
Renal function Measurement
eGFR (mL/min)
Criterion for stability
S1
G1
S2 (Within 3 to 14 days after S1)
G2
=|G2-G1|×100/G1a
If 25%; stable
If >25%; not stable
Abbreviations: S1= Screening Visit 1; S2= Screening Visit 2.
a.
Parenthesis of | | represents absolute values.


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4.2. Scientific Rationale for Study Design
This study is a phase 1, non-randomized, open-label, single-dose, parallel-group study of 
PF-06700841 in participants with severe renal impairment and participants with normal renal 
impairment (Part 1) and in participants with mild and moderate renal impairment (Part 2), 
matched for age, body weight and, to the extent possible, for gender composition.  Details on 
age and body weight matching criteria are specified in Section 4.1. 
Since PF-06700841 is primarily eliminated through a CYP450 mediated oxidation with 
CYP3A4 as the major contributor (fm = 0.62) and renal excretion as unchanged is minor 
(<16%), a reduced study design is proposed as suggested in the current draft guidance by 
FDA and EMA.2,6 In the reduced study, only participants with severe renal impairment and 
participants with normal renal function will be studied first. Therefore, the effect of renal 
impairment on PF-06700841 PK will be initially evaluated in the renally impaired population 
most likely to be of impact. The impact of renal impairment on expression of CYP enzymes, 
if any, is expected to be minimal and hence can also be evaluated in the severely renally 
impaired population to estimate the degree of impact. If the study results confirm that severe 
renal impairment does not alter PK to an extent that warrants dosage adjustment, no further 
study is warranted. If the results do not support such a conclusion, Part 2 will be conducted 
in participants with moderate and mild renal impairment, based on the decision criterion 
outlined in Section 4.1.
Single dose PF-06700841 PK appeared to be linear in the dose ranges of 1 - 100 mg, with 
more than dose-proportional increase especially in area under the concentration time curve 
from time 0 extrapolated to infinity (AUCinf) from 100 mg to 200 mg in the FIH study. In 
multiple dose period of the same study, both area under the concentration-time curve from 
time 0 to time (AUC) and Cmax appeared to increase proportionally with dose from 10 mg 
to 100 mg QD, with a trend towards greater than proportional increase from 100 mg to 
175 mg QD. No direct enzyme inhibition/induction or time-dependent enzyme inhibition has 
been identified in in vitro studies. Considering a linear PK at the therapeutic dose range 
being tested in Phase 2 studies (10 – 60 mg QD), in which single dose PK behavior can
predict multiple dose PK, a single dose study will be conducted to evaluate the PF-06700841
PK under conditions of renal impairment.
In the preliminary data of ADME study B7931014, PF-06802530 (M1) was identified as a 
major circulating metabolite, which was predominantly eliminated in the urine. The potential 
effects on the cardiovascular system for both PF-06700841 and PF-06802530 (M1) were 
evaluated in in vitro human ether-à-go-go-related gene (hERG) potassium channel assay. 
The hERG 50% inhibitory concentration (IC50) for PF-06700841 was 33.4 μM 
(13,000 ng/mL) and the 10% inhibitory concentration (IC10) is approximately 4 μM 
(1560 ng/mL), which are 49× and 5.9×, respectively, the predicted human unbound Cmax of 
264 ng/mL at a human dose of 60 mg QD. The IC50 for PF-06802530 (M1) was >50 μM 
(>20,300 ng/mL) and the IC10 was approximately 6.5 μM (2640 ng/mL), which are >77× and 
approximately 10× the predicted human unbound Cmax. Due to the QT prolongation concern 
of M1, combined with its primary elimination pathway of renal excretion, understanding of 
M1 exposure change in renal impairment is also important in addition to understanding 


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parent (PF-06700841) exposure change. Therefore, M1 plasma PK with or without renal 
impairment will be collected and characterized in this study.
PF-06700841 is not highly bound to human plasma proteins, with unbound fraction (fu) of 
0.61 observed in the in vitro protein binding study. Thus, no additional blood samples will 
be collected in this study for ex vivo protein binding analysis.
 
 
4.3. Justification for Dose
The study will use the PF-06700841 single dose of 30 mg, administered orally. Doses up to 
60 mg of PF-06700841 have been used in longer term efficacy and safety clinical trials. 
PF-06700841 30 mg is appropriate considering that systemic exposures of PF-06700841 and 
M1 may be increased in the presence of renal impairment.
Doses of PF-06700841 up to 200 mg single dose and 175 mg QD was generally safe and 
well-tolerated in the Phase 1 clinical study B7931001. There were no deaths, SAE, and 
serious infection reported in the study. Doses of PF-06700841 up to 60 mg QD was also 
generally safe and well-tolerated in PsO (B7931001 and B7931004) and AA participants 
(B7931005). There were no clinical meaningful findings in vital signs, ECG, suicidal 
behavior or ideation, or potential Hy’s Law cases reported during these studies.
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 Schedule of Activities.
The end of the study is defined as the date of the last scheduled procedure shown in the 
Schedule of Activities for the last participant in the trial.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and non-medical 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.
CCI


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5.1. Inclusion Criteria
5.1.1. All Participants
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants who are between the ages of 18 and 75 years, inclusive, 
at the Screening visit.

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. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
Weight:
3. Body mass index (BMI) of ≥17.5 to ≤40 kg/m2; and a total body weight >50 kg 
(110 lb). 
Informed Consent:
4. Capable of giving signed informed consent as described in Appendix 1
(Section 10.1), which includes compliance with the requirements and restrictions 
listed in the informed consent document (ICD) and in this protocol.
5.1.2. Additional Inclusion Criteria for Healthy Participants with Normal Renal 
Function (Cohort 2 only)
1. No clinically relevant abnormalities identified by a detailed medical history, full 
physical examination, including temperature, blood pressure (BP) and pulse rate 
measurement, 12-lead ECG and clinical laboratory tests.
2. Normal renal function (eGFR ≥90 mL/min) at 2 Screening visits based on the MDRD
equation. 
3. Demographically comparable to the group of participants with impaired renal 
function.

The each participant’s body weight within ±15 kg of the mean body weight of the 
severe renal impairment cohort (Cohort 1).

The each participant’s age within ±10 years of the mean age of the severe renal 
impairment cohort (Cohort 1).


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
Attempts will be made to ensure that the male-to-female composition of Cohort 2
is comparable to that in the severe renal impairment cohort (Cohort 1); cohorts 
cannot be comprised entirely of any one gender.

Other demographic characteristics, such as race and ethnicity, matched as closely 
as possible to the renal impairment cohort (Cohort 1).
5.1.3. Additional Inclusion Criteria for Participants with Impaired Renal Function 
(Cohort 1 and Cohorts 3 & 4 [if applicable] only)
1. Good general health commensurate with the population with chronic kidney disease
(renal impairment). “Health” is defined as no clinically relevant abnormalities 
identified by a detailed medical history, full physical examination, measurement of 
pulse rate and 12-lead ECG as well as clinical laboratory tests (except serum 
creatinine and eGFR). Hypertension, diabetes mellitus, hyperparathyroidism, 
ischemic heart disease and other common co-morbidities in this population are 
possible exemptions, as long as, in the opinion of the investigator, the participant is 
medically stable, is on a stable drug regimen, and can abide by the meals and dietary 
restrictions outlined in protocol Section 5.3.
2. Meet the following eGFR criteria during the screening period based on the MDRD 
equation: 

Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis. 

Moderate renal impairment (Part 2 only): eGFR ≥30 mL/min and 
<60 mL/min.

Mild renal impairment (Part 2 only): eGFR between 60 – 89 mL/min.
The eGFR values obtained at the 2 screening visits should not be more than 
25% different (see Section 4.1).
3. Any form of renal impairment except acute nephritic syndrome (participants with 
history of previous nephritic syndrome but in remission can be included).
4. Stable concomitant drug regimen (as defined in Section 6.5) for the management of 
individual participant’s medical conditions; on a case-by-case basis, with input from 
the sponsor, participants receiving fluctuating concomitant medication/treatment may 
be considered if the underlying disease is under control.


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5.2. Exclusion Criteria
5.2.1. All Participants
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Renal transplant recipients.
2. Urinary incontinenence without catheterization.
3. History of systemic infection requiring hospitalization, parenteral antimicrobial 
therapy, or as otherwise judged clinically significant by the investigator within 
6 months prior to Day 1.
4.
Known history of pulmonary embolism or recurrent deep vein thrombosis (DVT).
5. Active acute or chronic infection requiring treatment with oral antibiotics, antivirals, 
antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 1 or 
superficial skin infection within 1 week prior to Day 1.  NOTE: participants may be 
rescreened after the infection resolves.
6. Have evidence of untreated or inadequately treated active or latent infection with 
Mycobacterium tuberculosis (TB) infections as following (see details in Appendix 2).

A positive QuantiFERON-TB Gold (QFT-G) In-Tube test performed within the 
3 months prior to screening.  If the laboratory reports the test result as 
indeterminate, the test should be repeated.  If the result of the repeat test is 
indeterminate, a purified protein derivative (PPD) test may be substituted for the 
QFT-G In-Tube test only with approval from the Pfizer Medical Monitor on a 
case by case basis;
Note: 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 In-Tube test nor a 
PPD test need be obtained.
A participant who is being treated for latent or active TB infection is not eligible 
for this study.
7. History (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes 
zoster. 


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8. Known immunodeficiency disorder, including positive serology for human 
immunodeficiency virus (HIV) at screening, or a first-degree relative with a 
hereditary immunodeficiency.
9. Any present malignancies or history of malignancies with the exception of adequately 
treated or excised non-metastatic basal cell or squamous cell cancer of the skin or 
cervical carcinoma in situ.
10. History of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) related 
lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs and 
symptoms suggestive of current lymphatic or lymphoid disease.
11. Any condition possibly affecting drug absorption (eg, prior bariatric surgery, 
gastrectomy, ileal resection).
NOTE: participants who have undergone cholecystectomy and/or appendectomy 
are eligible for this study so long as the surgery occurred more than 6 months prior 
to Screening.
12. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or IP administration or may 
interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
13. Participants who have been vaccinated with live or attenuated vaccines within the 
6 weeks of dosing, or are to be vaccinated with these vaccines at any time during 
treatment or within 6 weeks following discontinuation of dosing.
14. Use of concomitant medications that prolong the QT interval within 10 days prior to 
first dose of IP or 5 half-lives (if known), whichever is longer. A list of these 
medications can be found at: http://www.crediblemeds.org.7
15. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 
5 half lives (whichever is longer) prior to Day 1. 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. 
Herbal supplements and hormone replacement therapy must be discontinued at least 
28 days prior to the first dose of investigational product; Depo-Provera® must be 
discontinued at least 6 months prior to dosing of investigational product. 
For participants with renal impairment, stable concomitant medications (including 
herbal supplements)  may be given following approval by the sponsor if they are 
considered necessary for the welfare of the study participants (eg, standard therapy 
for underlying diseases), are not contraindicated with the IP, and are unlikely to 
interfere with the PK of the IP. 


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Prior/Concurrent Clinical Study Experience:
16. Treatment with an investigational drug(s) within 30 days or 5 half-lives (whichever is 
longer) preceding the first dose of IP.
Diagnostic Assessments:
17. Infection with hepatitis B or hepatitis C viruses according to protocol-specific testing 
algorithm as described in Appendix 2 (Section 10.2.1). 
18. ANY of the following abnormalities in clinical laboratory tests at screening, and 
confirmed by a single repeat, if deemed necessary:
a.
Absolute neutrophil count <1.5 × 109/L (<1500/mm3);
b. Platelet count <150 × 109/L or <150,000/mm3;
c.
Absolute lymphocyte count of <0.8 × 109 /L (<800/mm3); 
d. Enzymes aspartate amino transaminase (AST) or alanine amino transaminase 
(ALT) values 
>2 × ULN;
e.
Total bilirubin >1.5 × ULN; participants with Gilbert’s syndrome would be 
eligible for this study provided the direct bilirubin is ≤ULN;
19. 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.
20. Screening laboratory tests with abnormal results may be repeated once to confirm 
abnormal results (with the same screening number); the last value will be used to 
determine eligibility.  
21. Sites may be permitted to re-screen participants (with a new screening number) who 
initially do not meet eligibility criteria once following agreement with the sponsor.
22. A positive urine drug test, for illicit drugs, at Screening: 
NOTE: repeat urine drug testing is not permitted in this study.

Renal impairment participants may be eligible to participate after approval from 
sponsor if their drug screen is positive for a prescribed substance that is not 
expected to interfere with the PK of PF-06700841.
23. ANY of the following conditions at screening:
a.
Screening 12-lead ECG that demonstrates:


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
Clinically significant abnormalities requiring treatment (eg, acute myocardial 
infarction, serious tachy- or brady-arrhythmias) or indicating serious 
underlying heart disease (eg, cardiomyopathy, Wolff-Parkinson–White 
syndrome); 

Confirmed QT interval corrected using Fridericia’s correction factor (QTcF) 
>450 msec for participants with normal renal function and >470 msec for 
participants with impaired renal function.
b. Long QT Syndrome, a family history of Long QT Syndrome, or a history of 
Torsades de Pointes. 
Other Exclusions:
24. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
Pfizer employees, including their family members, directly involved in the conduct of 
the study. 
25. History of regular alcohol consumption exceeding 7 drinks/week for females or 
14 drinks/week for males (1 drink = 5 ounces [150 mL] of wine or 12 ounces 
[360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months of Screening.
26. Female participants of childbearing potential who are unwilling or unable to use 
highly effective methods of contraception as outlined in Section 5.3.4 for the duration 
of the study and for at least 28 days after the administration of investigational 
product, pregnant female participants, female participants planning to become 
pregnant during the duration of the study until 28 days after the administration of 
investigational product, breastfeeding female participants.
27. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to the dose of investigational product.
28. History of sensitivity to heparin or heparin-induced thrombocytopenia, only if heparin 
is used to flush intravenous catheters used during serial blood collections.
29. Unwilling or unable to comply with the Lifestyle Considerations outlined in
Section 5.3.
5.2.2. Additional Exclusion Criteria for Healthy Participants with Normal Renal 
Function (Cohort 2, only)
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).


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2. Evidence or history of clinically significant dermatological condition (eg, contact 
dermatitis, AD, PsO) or visible rash present during physical examination.
3. 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.
4. Hemoglobin <11.0 g/dL (or 110 g/L).
5.2.3. Additional Exclusion Criteria for Participants with Impaired Renal Function 
(Cohort 1 and Cohorts 3 & 4 [if applicable] only)
1. Participants requiring hemodialysis and/or peritoneal dialysis. 
2. Participants with other clinically significant disease that may affect the safety of the 
participant or that may affect the PK of PF-06700841 (including drug allergies, but 
excluding untreated, asymptomatic, seasonal allergies at time of dosing). Participants 
with any significant hepatic, cardiac, or pulmonary disease or participants who are 
clinically nephrotic.  Hypertension, diabetes mellitus, hyperparathyroidism, ischemic 
heart disease, etc. are not cause for exclusion as long as, in the opinion of the 
investigator, the participant is medically stable and any drugs that are administered 
for these conditions are not expected to interfere with the PK of PF-06700841. 
3. Screening BP ≥180 mm Hg (systolic) or ≥110 mm Hg (diastolic), following at least 
5 minutes of supine rest.  If initial BP is ≥180 mm Hg (systolic) or ≥110 mm Hg 
(diastolic), the BP should be repeated two more times and the average of the 3 BP 
values should be used to determine the participant’s eligibility.
4. Hemoglobin <10 g/dL (or 100 g/L) for participants not receiving erythropoietin, or 
<9.0 g/dL (or 90 g/L) for participants receiving erythropoietin.
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Meals and Dietary Restrictions

Participants must abstain from all food and drink (except water) at least 4 hours prior 
to any safety laboratory evaluations and 10 hours prior to the collection of the predose 
PK sample and investigational product administration on Day 1. There will be no
restriction to breakfast on the other days provided other restrictions are followed.

Water is permitted until 1 hour prior to IP administration. Water may be consumed 
without restriction beginning 1 hour after dosing.  Noncaffeinated drinks (except 
grapefruit or grapefruit related citrus fruit juices see below) may be consumed with 
meals and the evening snack.


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
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 not be allowed to eat or drink grapefruit or grapefruit-related citrus 
fruits (eg, Seville oranges, pomelos) from 7 days prior to the investigational product 
administration until collection of the final PK blood sample. 

While confined, the 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 
dosing until collection of the final PK sample of each study period. Participants will 
additionally abstain from caffeine-containing products at least 2 hours prior to any 
scheduled vital sign and ECG measurements.

Participants will abstain from alcohol for 24 hours prior to admission to the CRU and 
continue abstaining from alcohol until collection of the final PK sample.  Participants 
may undergo an alcohol breath test or blood alcohol test at the discretion of the 
investigator.

Participants will abstain from the use of tobacco- or nicotine-containing products for 
24 hours prior to dosing and during confinement in the CRU.
5.3.3. Activity

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
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 Schedule of Activities, the investigator or designee will inform 
the participant of the need to use highly effective contraception consistently and correctly 


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and document the conversation and the participant’s affirmation in the participant’s chart 
(participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception).  In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently entered in the study. Screen failure data are collected and remain as 
source and are not reported to the clinical database.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened if prior reason for not meeting the eligibility criteria has been resolved.  
Rescreening may only occur with sponsor approval.  In the event that the participation of a 
participant in the study is delayed, outdated screening procedures can be repeated.  
Rescreened participants should be assigned the same participant number as for the initial 
screening.  
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Interventions Administered
For this study, the investigational product is PF-06700841 (provided as 5 and 25 mg tablets).
PF-06700841 5 and 25 mg tablets will be supplied by Pfizer to the CRU in bulk along with 
individual dosing containers for unit dosing.
6.1.1. Administration
Investigational products will be administered orally and according to the conditions 
described in the Schedule of Activities section and Meals and Dietary Restrictions section of 
this protocol.
Following an overnight fast of at least 10 hours, participants will receive 30 mg 
PF-06700841 tablets (as 1 × 5 mg and 1 × 25 mg) at approximately 08:00 hours (plus or 
minus 2 hours) on Day 1 with approximately 240 mL ambient temperature water. 
Participants will swallow the 2 tablets of PF-06700841 whole, and will not manipulate or 
chew the investigational product prior to swallowing.


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In order to standardize the conditions on PK sampling days, all participants will be required 
to refrain from lying down (except when required for BP, pulse rate, and ECG 
measurements), eating, and drinking beverages other than water during the first 4 hours after 
PF-06700841 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, as 
applicable for temperature-monitored shipments. 
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 temperature since previously documented for all 
site storage locations upon return to business.
3. 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). All study 
interventions will be accounted for using an investigational product accountability 
form/record.
4. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label. 
6. Study interventions should be stored in their original containers and in accordance
with the label. 
7. Deviations from the storage requirements, including any actions taken, must be 
documented and reported to Pfizer upon discovery.  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.  It will not be considered a protocol deviation if Pfizer approves the use 
of the study intervention after the temperature excursion. Use of the study 
intervention prior to Pfizer approval will be considered a protocol deviation. 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.


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8. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  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, and all destruction must be adequately 
documented.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the investigational product ready for administration or dispensing to the participant by 
qualified staff.  Dispensing is defined as the provision of investigational product, 
concomitant treatments, and accompanying information by qualified staff member(s) to a 
healthcare provider, participant in accordance with this protocol.  Local health authority 
regulations or investigator site guidelines may use alternative terms for these activities.
PF-06700841 tablets 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). The tablets 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 Investigational Product
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.  All participants enrolled will receive treatment according to the dose/schedule.
6.4. Study Intervention Compliance
Investigational product will be administered under the supervision of investigator site 
personnel.  The oral cavity of each participant will be examined following dosing to ensure 
the investigational product was taken.
6.5. Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of 
investigational product.  Limited use of nonprescription medications that are not believed to 
affect participant safety or the overall results of the study may be permitted on a case-by-case 
basis following approval by the sponsor.
Acetaminophen/paracetamol may be used at doses of ≤3 g/day.


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Females using hormonal contraceptives or taking hormone replacement therapy may be 
eligible to participate in this study if they are willing to discontinue therapy at least 28 days 
prior to the first dose of study treatment and remain off hormonal therapy for the duration of 
the study.  Depo-Provera® must be discontinued at least 6 months prior to the first dose of 
study treatment. Note that another approved method of contraception must then be used 
(Section 10.4.4).
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 investigational product will be 
documented as a prior treatment.  Treatments taken after the first dose of investigational 
product will be documented as concomitant treatments.
6.5.1. Participants with Healthy Renal Function (Cohort 2 Only)
In general, participants will abstain from all concomitant treatments (prescription or over the 
counter) as described in the Exclusion Criteria section of the protocol, except for the
treatment of AEs. Of note, the following restrictions apply:

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 
after approval by the sponsor.
6.5.2. Participants with Impaired Renal Function (Cohort 1 and Cohorts 3 & 4 [if 
applicable])
Participants are permitted to be on stable doses of background medications if they are 
considered necessary for the welfare of the study participants (eg, standard therapy for the 
underlying disease), are not contraindicated with the investigational product, and are unlikely 
to interfere with the PK of the investigational product. Whenever possible, attempts must be 
made to not alter the doses and regimens of the concomitant medications after Day 1 and 
until the end of study on Day 4.

Approved concomitant medications should be administered to renally impaired 
participants at least 2 hours prior to dosing or withheld until 4 hours after PF-
06700841 dosing.
6.6. Dose Modification
Dose modifications for PF-06700841 are not allowed.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants after 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 
investigational product.  If investigational product is permanently discontinued, the 
participant will remain in the study to be evaluated for safety. 
See the Schedule of Activities for data to be collected at the time of intervention 
discontinuation and follow-up and for any further evaluations that need to be completed.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted.  See the Schedule of Activities 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 randomized and then are 
prematurely withdrawn from the study.  Participants should be questioned regarding their 
reason for withdrawal.  
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples, but data already generated from the samples will continue to be available, and may 
be used to protect the integrity of existing analyses.  The investigator must document any 
such requests in the site study records.
If the participant withdraws from the study and also withdraws consent (see below) 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 case report form (CRF) and reported on the Clinical Trial (CT) SAE Report.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Withdrawal of Consent: 
Participants who request to discontinue receipt of study treatment 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 


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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 investigational product 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. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
Participants will be screened within 28 days prior to administration of the investigational 
product to confirm that they meet the study population criteria for the study.  The investigator 
(or an appropriate delegate at the investigator site) must obtain a signed and dated ICD 
before performing any study-specific procedures.  If the time between screening and dosing 
exceeds 28 days as a result of unexpected delays (eg, delayed drug shipment), then 
participants do not require rescreening if the laboratory results obtained prior to first dose 
administration meet eligibility criteria.
A participant who qualified for this protocol but did not enroll from an earlier group may be 
used in the study without rescreening, provided laboratory results obtained prior to the first 
dose administration meet eligibility criteria for this study.  
 
 
 
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Study procedures and their timing are summarized in the Schedule of Activities.  Protocol
waivers or exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
If an intravenous (IV) catheter is utilized for blood sample collections, ECGs and vital sign 
assessments (pulse rate, temperature and BP) should be collected prior to the insertion of the 
catheter.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately 
88 mL.  The actual collection times of blood sampling may change.  Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 60 consecutive 
days.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.
8.1. Efficacy Assessments
Not applicable.


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8.2. Safety Assessments
Planned time points for all safety assessments are provided in the Schedule of Activities.  
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety concerns.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems.
A limited physical examination will include, at a minimum, assessments of general 
appearance, the respiratory and cardiovascular systems, and participant-reported symptoms.
Physical examinations may be conducted by a physician, trained physician’s assistant, or 
nurse practitioner as acceptable according to local regulation. 
Height and weight will also be measured and recorded as per the Schedule of Activities.  For 
measuring weight, a scale with appropriate range and resolution is used and must be placed 
on a stable, flat surface. Participants must remove shoes, bulky layers of clothing, and 
jackets so that only light clothing remains.  They must also remove the contents of their 
pockets and remain still during measurement of weight.
8.2.2. Vital Signs
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest.  The same arm 
(preferably the dominant arm) will be used throughout the study.  Participants should be 
instructed not to speak during measurements.
The same properly sized and calibrated BP cuff will be used to measure BP each time.  The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds.  When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
In some cases, it may be appropriate to repeat abnormal vital signs to rule out measurement 
errors due to eg, improperly placed BP measurement cuff.
8.2.2.1. Temperature
Temperature will be measured orally (other body locations, eg tympanic, are acceptable 
provided the same method is used and documented throughout the study).  No eating, 
drinking, or smoking is allowed for 15 minutes prior to the measurement.


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8.2.3. Electrocardiograms
Twelve (12)-lead ECGs should be collected at times specified in the Schedule of Activities of 
this protocol using an ECG machine that automatically calculates the heart rate and measures 
PR, QT, and QTc intervals and QRS complex.  All scheduled ECGs should be performed 
after the participant has rested quietly for at least 10 minutes in a supine position. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements (predose on Day 1). Additional ECG monitoring will 
occur if a) a postdose QTc interval remains ≥30 msec from the baseline and is >450 msec for 
participants with normal renal function (Cohort 2) and >470 msec for participants with 
impaired renal function (Cohort 1, 3, and 4); 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 ≥30 msec from the baseline and is >450 msec for 
partipants with normal renal function (Cohort 2) and >470 msec for participants with 
impaired renal function (Cohort 1, 3, and 4); or b) an absolute QTc value is ≥500 msec for 
any scheduled ECG for greater than 4 hours (or sooner, at the discretion of the investigator),
or QTc intervals get progressively longer, the participant should undergo continuous ECG 
monitoring.  A cardiologist should be consulted if QTc intervals do not return to less than the 
criterion listed above after 8 hours of monitoring (or sooner, at the discretion of the 
investigator). 
ECG data will be submitted to a central laboratory for measurement.  The final ECG report 
from the central laboratory should be maintained in the participant’s source documentation 
and be the final interpretation of the ECG recording.  Any clinically significant changes from 
the baseline/Day 1 ECG may potentially be AEs (Appendix 7) and should be evaluated 
further, as clinically warranted.  
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 should be performed before laboratory blood collection.
A paper or digital copy of the ECG should be filed in the participant’s chart and must be 
available to the sponsor upon request.  Any clinically significant changes will be recorded 
and evaluated further, as clinically warranted.  Participants will be discontinued from study 
with a confirmed QTc >500 milliseconds or a confirmed QTc change from baseline of 
>60 milliseconds.


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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 
Schedule of Activities for the timing and frequency.
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 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.
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted 
in accordance with the laboratory manual and the Schedule of Activities.
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
Participants may undergo random urine drug testing at the discretion of the investigator.  
Drug testing conducted prior to dosing must be negative for participants to receive 
investigational product.
8.2.5. 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
Schedule of Activities.  WOCBP must be using be using a permitted contraceptive method to 
be eligible for study participation (see Appendix 4 Section 10.4.3). 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 investigational product.  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 institutional review boards (IRBs)/ethics committees (ECs) or if 
required by local regulations. 


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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant’s legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or that caused the participant to discontinue the 
study (see Section 7). 
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 investigational product), through and including 
a minimum of 28 calendar days after the last administration of the investigational product(s).
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the CRF, not the AE section.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation.  However, if the investigator learns of any SAE, including a death, at any time 
after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form immediately 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.


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SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
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, institutional review boards (IRBs)/ECs, and 
investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.


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An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the investigator’s brochure 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 investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study intervention and until 28 days after the 
last dose.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.5.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  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’s administration, the SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information 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. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
products by the wrong participant, or at the wrong time, or at the wrong dosage strength.


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Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the investigational products;

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 immediately.
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 an 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 PF-06700841 greater than 200 mg within a 24-hour time period 
will be considered an overdose.
There is no specific antidote for PF-06700841, therefore Pfizer dose not recommend specific 
treatment for an overdose of PF-06700841.
In the event of an overdose, the investigator should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities until 
PF-06700841 can no longer be detected systemically (at least 4 days).


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3. 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).
4. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
5. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics
8.5.1. Plasma for Analysis of PF-06700841 and M1
Two (2) blood samples of approximately 3 mL to provide a minimum of 1.2 mL, will be 
collected into appropriately labeled tubes containing potassium ethylenediaminetetraacetic 
acid (K2EDTA) for measurement of plasma concentrations of PF-06700841 and M1,
respectively, at times specified in the Schedule of Activities.  The appropriate additive will
be added to the sample collected for M1 PK.  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 IP 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 IP 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 PF-06700841 and M1.  Samples collected for 
analyses of PF-06700841 and/or M1 plasma 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, 
 
.
Genetic analyses will not be performed on these plasma samples.  Participant confidentiality 
will be maintained.
Samples collected for measurement of plasma concentrations of PF-06700841 and M1 will 
be analyzed using a validated analytical method in compliance with applicable standard 
operating procedures (SOPs).
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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.
8.5.2. Urine for Analysis of PF-06700841 and M1
Urine will be collected at the intervals outlined in Schedule of Activities.  Each participant
will empty his/her bladder just prior to dosing.  During the subsequent designated urine 
collection intervals ([0-24], [24-48], and [48-72] hours post dose), participants will void ALL 
urine produced during the designated collection interval, including a forced void at the end of 
the collection interval, directly into pre-weighed urine collection container.  Each collection 
interval should have it’s own collection container(s).  During the entire collection interval, 
the container(s) should be stored at 4°C. At the end of each urine collection interval, all 
urine collected will be thoroughly mixed, total weight of urine will be determined first 
(weigh the empty container first and then weigh the container at the end of the collection)
and then the volume of urine will be calculated by assuming specific gravity of urine = 1 and 
recorded on the CRF. An urine aliquot will be withdrawn for measurement of drug 
concentrations.  
Additional details for collection, processing and storage of urine for analysis of PF-06700841
and M1 will be added to the laboratory manual and provided to the investigator site prior to 
the start of the study.
Urine samples will be analyzed using a validated analytical method in compliance with 
Pfizer SOPs, only if it is determined by the study team that there is a need to do so, based on 
review of plasma PK results for PF-06700841 and M1.
8.6. Pharmacodynamics
Pharmacodynamic (PD) parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
 
 
 
 
 
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8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor. The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Statistical Hypotheses
No statistical hypothesis will be tested in this study.
9.2. Sample Size Determination
In Part 1, approximately 8 participants will be enrolled into the normal renal function group 
and the severe renal impairment group to ensure approximately 6 evaluable completers in 
each group. If Part 2 is conducted, approximately 8 participants will be enrolled to the mild 
and moderate renal groups to ensure approximately 6 evaluable completers per group. The 
sample size is based on recommendations from the “FDA Guidance for 
Industry - Pharmacokinetics in Patients with Impaired Renal Function-Study Design, Data 
Analysis, and Impact on Dosing and Labeling”.8
Participants who discontinue from the study before completing all assessments may be 
replaced at the discretion of the investigator and sponsor.
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9.3. Populations for Analysis
For purposes of analysis, the following populations are defined:
Population
Description
PK Concentration
The PK concentration population is defined as all participants 
assigned to investigational product and treated who have at 
least 1 concentration measured.
PK Parameter
The PK parameter analysis population is defined as all 
participants assigned to investigational product and treated who 
have at least 1 of the PK parameters of primary interest
measured.
Safety
All assigned to investigational product and who take at least 
1 dose of investigational product.  
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.
Part 1
Analysis of variance (ANOVA) will be used to compare the natural log transformed AUCinf
and Cmax for PF-06700841 and M1 between normal renal function group (Reference) and the 
severe impaired renal function group (Test).  Estimates of the adjusted mean differences 
(Test-Reference) and corresponding 90% confidence intervals (CIs) will be obtained from 
the model.  The adjusted mean differences and 90% CIs for the differences will be
exponentiated to provide estimates of the ratio of the adjusted geometric means 
(Test/Reference) and 90% CIs for the ratios.
Part 2 may be conducted if either PF-06700841 or M1 AUCinf GMR for severe renal 
impairment group compared to normal group is ≥1.5.
Part 2
ANOVA will be used to compare the natural log transformed AUCinf and Cmax for 
PF-06700841 and M1 between normal renal function group (Reference) and the moderate 
and mild impaired renal function groups (Test).  Estimates of the adjusted mean differences 
(Test-Reference) and corresponding 90% CIs will be obtained from the model.  The adjusted 
mean differences and 90% CIs for the differences will be exponentiated to provide estimates 
of the ratio of the adjusted geometric means (Test/Reference) and 90% CIs for the ratios. If 


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substantial differences in demographic characteristics between healthy and impaired 
participants are observed, weight and age may be explored as covariates.
Box and whisker plots for individual participant parameters (AUCinf and Cmax) will be
constructed by renal function group and overlaid with geometric means.
For summary statistics and median/mean plots by sampling time, the nominal PK sampling 
time will be used.  For individual participant plots by time, the actual PK sampling time will 
be used.
If Part 2 is executed and data for normal, mild, moderate and severe impairment groups are
available, additional analysis will be performed to assess relationship between appropriate 
PK parameters and renal function.
Linear regression will be used to analyze the potential relationship between appropriate PK
parameters (
 renal clearance [CLr],
) and renal function (eGFR). Estimates 
of the slope and, intercept, together with their precision (90% CI), and the coefficient of 
determination will be obtained from the model.
Plots of PK parameters (
 CLr, 
) versus renal function (eGFR) will be 
constructed. A regression line and 90% confidence region for the PK parameters and eGFR
will be included if appropriate. Vertical lines for the renal function group cut-off values will 
also be presented on the plots. Different symbols will be used to identify participants from 
different renal function groups.
9.4.1. Efficacy Analyses
An efficacy analysis is not applicable to this study. 
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
AEs, ECGs, BP, pulse rate, and safety laboratory data will be reviewed and summarized on 
an ongoing basis during the study to evaluate the safety of participants.  Any clinical 
laboratory, ECG, BP, and pulse rate abnormalities of potential clinical concern will be 
described.  Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered source data and will 
not be required to be reported, unless otherwise noted.  However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE. 
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted.  Demographic data collected at screening will be reported.
CCI
CCI
CCI
CCI


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9.4.2.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
The number (%) of participants with maximum post-dose QTc values and maximum 
increases from baseline in the following categories will be tabulated by treatment:
Table 3.
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
-
30-60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
 
 
 
9.4.3.1. Pharmacokinetic Analyses
9.4.3.1.1. Analysis Population
The PK concentration population will be defined as all participants treated in whom at least 
1 plasma concentration value is reported.
The PK parameter analysis population is defined as all participants dosed who have at least 
1 of the PK parameters of primary interest.
9.4.3.1.2. Derivation of Pharmacokinetic Parameters Prior to Analysis
The plasma PK parameters for PF-06700841 and M1 following single dose administration 
will be derived from the concentration time profiles as detailed in Table 4.  Actual PK 
sampling times will be used in the derivation of PK parameters.  In the case that actual PK 
sampling times are not available, nominal PK sampling time will be used in the derivation of 
PK parameters.
CCI


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Table 4.
Plasma PK Parameters
Parameter
Analyte
Definition
Method of Determination
 
 
AUCinf*
PF-06700841, M1
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.
AUC72
PF-06700841, M1
Area under the plasma 
concentration-time profile from 
time 0 to 72 hours post dose
Linear/Log trapezoidal method.
Cmax
PF-06700841, M1
Maximum plasma concentration
Observed directly from data.
 
 
 
 
 
 
* As data permit.
If urine samples need to be analyzed (See Section 8.5.2), the following urine PK parameters 
(Table 5) will be calculated for PF-06700841 and M1 (as data permit):
Table 5.
Urine PK Parameters
Parameter
Analyte
Definition
Method of Determination
Ae72
PF-06700841, M1
Total amount of unchanged drug 
excreted in the urine over 72 hours
Sum of amount excreted for each 
collection period.
Ae72% 
PF-06700841, M1
Total amount of unchanged drug 
excreted in the urine over 72 hours, 
expressed as percent of dose
100×(Ae72/Dose)
CLr
PF-06700841, M1
Renal clearance
Ae72/AUC72
Urine PK parameters will be analyzed and summarized using descriptive statistics.
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.
CCI
CCI
C
C
I
CCI
CCI


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9.5.1. Data Monitoring Committee 
This study will not use a data monitoring committee (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 Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, 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 Code of Federal Regulations (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 investigational 
product, 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 subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study.
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, Health Insurance Portability and Accountability Act
(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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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 form and 
will be password protected 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 shall 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 natural persons 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.  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 European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.


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EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (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 contribute to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.


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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 form and are password protected to prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.


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10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed 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 Data Handling Plan.
10.1.8. Study and Site Closure
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 contract 
research organization (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.
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 end of the study (or 
study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results.


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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 study team on demand (SToD) 
system. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or 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 6) will be performed at times defined in the 
Schedule of Activities 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 6.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (Abs 
and %)
Eosinophils (Abs and %)
Monocytes (Abs and %)
Basophils (Abs and %)
Lymphocytes (Abs and 
%)
BUN/urea and 
creatininea
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Albumin
Total protein
Uric acid
Creatine kinase
Additional Assessments 
for Hy’s Law:
AST, ALT (repeat)
Total bilirubin (repeat)
Albumin (repeat)
Alkaline phosphatase 
(repeat)
Creatine kinase (repeat)
Direct bilirubin
Indirect bilirubin
GGT
PT/INR
Total bile acids
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopyb

FSHc

Pregnancy test 
(β-hCG)d

eGFR

HBsAge

HBcAbe

HbsAbe

HCVAbe

HIVe

QuantiFERON-TB 
Gold Test or PPDe

Breath or urine alcohol 
testf

Urine drug screeningg

Urine myoglobinh
Abbreviations: Abs = absolute; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
β-hCG = beta-human chorionic gonadotropin; BUN = blood urea nitrogen; CO2 = carbon dioxide; 
eGFR = estimated glomerular filtration rate; FSH = follicle-stimulating hormone; GGT = gamma-glutamyl 
transferase; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B 
surface antigen; hCG = human chorionic gonadotropin; HCVAb = hepatitis C antibody; HIV = human 
immunodeficiency virus; INR = international normalized ration; MCH = mean corpuscular hemoglobin; 
MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; PT = prothrombin
time; qual = qualitative; RBC = red blood cell; S1= Screening Visit 1; 
S2= Screening Visit 2; THC = tetrahydrocannabinol; ULN = upper limit of normal; WBC = white blood cell. 


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a.
Only serum creatinine on Screening Day 2 (S2) for eGFR assessment.
b.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
c.
At Screening (S1) for confirmation of postmenopausal status only.
d.
Urine or Serum -hCG for female participants of childbearing potential according to Schedule of 
Activities.
e.
Complete at screening (S1).  Previous testing for QuantiFERON-TB Gold Test will be accepted if 
completed within 3 months prior to screening.  Otherwise should be completed at screening and results 
available prior to Day -1. If QFT-G test cannot be performed, or if results cannot be determined positive 
or negative, participants may be screened using PPD Tuberculin Test (Mantoux method) with approval 
of medical monitor. HBsAb will be performed as reflex testing for any participant who is HBsAg 
negative but HBcAb positive.  HCV RNA will be performed as reflex testing for any participant who is 
HCV Ab positive.
f.
Complete at screening (S1) and Day -1.
g.
At Screening (S1) and Day -1. The minimum requirement for drug screening includes cocaine, 
tetrahydrocannabinol (THC), opiates/opioids, benzodiazepines, and amphetamines (others are site and 
study specific).
h.
Reflex testing for creatine kinase >10 × ULN.
Investigators must document their review of each laboratory safety report.
Participants may undergo random urine drug testing at the discretion of the investigator.  
Drug testing prior to dosing must be negative for participants to receive investigational 
product.
10.2.1. Hepatitis B and C Testing Algorithm and Full Eligibility Criteria
All participants will undergo screening for hepatitis B and C for eligibility.
At screening, HBsAg and HBcAb will be tested:
a.
If both tests are negative, the participant is eligible for study inclusion.
b. If HBsAg is positive, the participant must be excluded from participation in the study.
c.
If HBsAg is negative and HBcAb is positive, HBsAb reflex testing is required:
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. 
At screening, HCVAb will be tested:
a.
Participants who are HCVAb positive will be reflex-tested for HCV RNA.
b. Participants who are positive for HCVAb and HCV RNA will not be eligible for this 
study.


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10.2.2. Tuberculosis Testing
During the Screening period, it must be determined and documented that a participant does 
not have evidence of untreated or inadequately treated active or latent infection with 
Mycobacterium tuberculosis (TB) per exclusion criterion #6 (Section 5.2.1).  The results of 
TB screening conducted within 3 months prior to screening or during the Screening period 
must be documented in study records prior to Baseline.
QFT-G In-Tube test is the preferred testing method.  If the laboratory reports that the QFT-G 
test results are indeterminate, the test should be repeated. If the result of the repeat test is 
indeterminate, then participants may be screened using the PPD Tuberculin Skin Test 
(Mantoux method) with approval of the Pfizer Medical Monitor.
10.2.2.1. Purified Protein Derivative Test
If the QFT-G In-Tube test cannot be performed or if the QFT-G results are indeterminate, 
then participants may be screened using the PPD Tuberculin Test (Mantoux method) if 
approved by the Pfizer medical monitor.
Participants must have the PPD test administered and evaluated by a health care professional 
48 to 72 hours later in order to be eligible for the study.  The test should be performed 
according to local standards (eg, induration of <5 mm being a negative result).


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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 (ie, not related to progression of 
underlying disease).

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.
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 investigational product 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 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.


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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 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
None
All (and exposure during 
pregnancy [EDP] 
supplemental form for 
EDP)  

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: 

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.


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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.

If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” 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.


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Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.

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 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 


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courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.


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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which
corresponds to the time needed to eliminate study intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and
agree to remain abstinent. 
OR

Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described below 
(Section 10.4.4) during the intervention period and for at least 28 days after the last 
dose of study intervention, which corresponds to the time needed to eliminate any 
study intervention(s).

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.


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10.4.3. Woman of Childbearing Potential (WOCBP)
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. Premenarchal.
2. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in the 
participant’s medical record for the study.
3. Postmenopausal female.

A postmenopausal state is defined as age 60 years or older or no menses for 
12 months without an alternative medical cause. 

A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT).

Females on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.


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10.4.4. Contraception Methods
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS).
4. Bilateral tubal occlusion.
5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed.  If not, an additional highly effective method of contraception 
should be used.  The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent
1. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation.

Oral;

Intravaginal;

Transdermal;

Injectable.
2. Progestogen-only hormone contraception associated with inhibition of ovulation.

Oral;

Injectable.
3. 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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Collection of Pregnancy Information
For both unapproved/unlicensed products and for marketed products, an EDP occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the investigational product, 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.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
participant reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) to Pfizer Safety using the EDP supplemental form.  This must be done 
irrespective of whether an AE has occurred and within 24 hours of awareness of the 
exposure.  The information submitted should include the anticipated date of delivery (see 
below for information related to termination of pregnancy).
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).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;


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
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product. 
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.


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CCI


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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 drug-induced 
liver injury (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 total bilirubin (TBili) 
elevations (>2 × ULN) by several days or weeks.  The increase in TBili typically occurs 
while AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample).  In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased.  This occurrence is still regarded as a 
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).


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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the liver function test (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 Adverse Events (AEs)

Marked sinus bradycardia (rate <40 beats per minute [bpm]) lasting minutes.

New PR interval prolongation >280 millisecond (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) atrioventricular (AV) block of 
>30 seconds’ duration.

Frequent premature ventricular complexes (PVCs), triplets, or short intervals 
(<30 seconds) of consecutive ventricular complexes.
ECG Findings That May Qualify as Serious Adverse Events (SAEs)

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia. 

Asystole:

In awake, symptom-free participants in sinus rhythm, with documented periods 
of asystole 3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node. 

In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (rate 
<40 bpm), accelerated idioventricular rhythm (40< x <100), and 


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monomorphic/polymorphic ventricular tachycardia >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 Serious Adverse Events

Change in pattern suggestive of new myocardial infarction. 

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.


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10.8. Appendix 8: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AA
alopecia areata
Abs
absolute
AD
atopic dermatitis
ADME
Absorption, Distribution, Metabolism and Elimination
AE
adverse event
ALT
alanine aminotransferase
ANOVA
analysis of variance
AST
aspartate aminotransferase
AUC
area under the curve
AUC24
area under the concentration-time curve from time 0 to 24 hours
AUCinf
area under the concentration-time curve from time 0 to infinity
AUClast
area under the concentration-time curve from 0 to time of last 
measurable concentration
AUCτ
area under the concentration-time curve from time 0 to time τ
AV
atrioventricular
β-hCG
beta-human chorionic gonadotropin
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BSA
body surface area
BUN
blood urea nitrogen
CD
Crohn’s disease
CFR
Code of Federal Regulations
C-G
Cockcroft Gault
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD
Chronic Kidney Disease
CLcr
creatinine clearance
CLr
renal clearance
Clast
last quantifiable concentration
Cmax
maximum plasma concentration
CO2
carbon dioxide (bicarbonate)
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
CCI
CCI


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Abbreviation
Term
CT
clinical trial
CYP450
cytochrome P450
DC
discontinuation
DCT
data collection tool
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DVT
deep vein thrombosis
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
FDA
Food and Drug Administration
FIH
first-in-human
fm
fraction metabolized
FSH
follicle-stimulating hormone
fu
unbound fraction
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
GMR
geometric mean ratio 
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg 
hepatitis B surface antigen
hCG
human chorionic gonadotropin
HCV
hepatitis C
HCVAb
hepatitis C antibody
HDL
lipoprotein
hERG
human ether-à-go-go-related gene
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
HS
hidradenitis suppurativa
IB
investigator’s brochure
IBD
inflammatory bowel disease
IC10
10% inhibitory concentration
IC50
50% inhibitory concentration
ICD
informed consent document


PF-06700841
Protocol B7931048
Final Protocol, 20 November 2019
PFIZER CONFIDENTIAL
Page 86
Abbreviation
Term
ICH
International Council for Harmonisation
IFN
interferon
IL
interleukin
IND
investigational new drug 
INR
international normalized ratio
IRB
institutional review board
IUD
intrauterine device
IUS
intrauterine hormone releasing system
IV
intravenous
JAK
Janus kinase
K2EDTA
ethylenediaminetetraacetic acid
KDOQI
Kidney Disease Outcomes Quality Initiative
LDL
low density lipoprotein
LFT
liver function test
MAD
multiple ascending dose
MATE
multidrug toxin extrusion protein
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDRD
Modification of Diet in Renal Disease
msec
millisecond
N/A
not applicable
NOAEL
no-observed-adverse-effect level
OCT2
organic cation transport 2
P-gp
p-glycoprotein
PASI
Psoriasis Area and Severity Index
PCD
primary completion date
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PPD
purified protein derivative
PsA
psoriatic arthritis
PsO
psoriasis
PT
prothrombin time
PVC
premature ventricular contraction/complex
QD
once daily
QTc
corrected QT
QTcF
QT interval corrected using Fridericia’s correction factor
QFT-G
QuantiFERON-TB Gold
qual
qualitative
QW
once a week
RBC
red blood cell
RNA
ribonucleic acid
SAD
single ascending dose


PF-06700841
Protocol B7931048
Final Protocol, 20 November 2019
PFIZER CONFIDENTIAL
Page 87
Abbreviation
Term
SAE
serious adverse event
SAP
statistical analysis plan
SCr
serum creatinine
SLE
systemic lupus erythematosus
SoA
schedule of activities
SOC
system organ class
SOP
standard operating procedure
SRSD
single reference safety document
SToD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
t½
terminal elimination half-life
TB
tuberculosis
TEAEs
treatment emergent adverse events
TBili
total bilirubin
Th17
T help 17
THC
tetrahydrocannabinol
Tmax
time to maximum concentration
TYK2
tyrosine kinase 2
UC
ulcerative colitis
ULN
upper limit of normal
US
United States
WBC
white blood cell
WOCBP
woman of childbearing potential
CCI


PF-06700841
Protocol B7931048
Final Protocol, 20 November 2019
PFIZER CONFIDENTIAL
Page 88
11. REFERENCES
1.
National Kidney Foundation. (2002) K/DOQI Clinical practice guidelines for chronic 
kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 39(2 
Suppl 1):S1-266.
2.
Guideline on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients 
with Decreased Renal Function. EMA Committee for Medicinal Products or Human use.  
20 Feb 2014.
3.
Nalbandian A, Crispin JC, Tsokos GC. Interleukin-17 and systemic lupus 
erythematosus: current concepts. Clin Exp Immunol 2009; 157(2):209-15.
4.
Ardoin ST and Pisetsky DS.  Developments in the scientific understanding of lupus. 
Arthritis Res Ther 2008; 10(5):218.
5.
Schwatzman-Morris J and Putterman C. Gender differences in the pathogenesis and 
outcome of lupus and of lupus nephritis. Clin Dev Immunol 2012; 2012:1-9.
6.
FDA. Draft Guidance for Industry: Pharmacokinetics in Patients with Impaired Renal 
Function — Study Design, Data Analysis, and Impact on Dosing and Labeling; March 
2010. Accessed 07 December 2017. 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Gui
dances/UCM204959.pdf.
7.
Woosley RL, Heise CW, Gallo T, Tate J, Woosley D and Romero KA, 
www.CredibleMeds.org, QTdrugs List, (Accessed on 15 Apr 2019), AZCERT, Inc. 
1822 Innovation Park Dr., Oro Valley, AZ 85755.
8.
Guidance for Industry: Pharmacokinetics in Patients with Impaired Renal Function 
Study Design, Data Analysis, and Impact on Dosing and Labeling. FDA Guidance,
March 2010.

SAP_001.pdf: 
Protocol B7931048 (PF-06700841) Statistical Analysis Plan
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PFIZER CONFIDENTIAL
Protocol B7931048
A PHASE 1, NON-RANDOMIZED, OPEN LABEL, SINGLE DOSE 
STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND
TOLERABILITY OF PF-06700841 IN PARTICIPANTS WITH RENAL 
IMPAIRMENT AND IN HEALTHY PARTICIPANTS WITH 
NORMAL RENAL FUNCTION
Statistical Analysis Plan 
(SAP)
Version:
1.0
SAP Author: 
(FSP Statistician –
 
)
Date:
18-Feb-2020
PPD
PPD


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Revision History
Version
Date
Author(s)
Summary of Changes/Comments
1.0
February 18, 2020 
Not Applicable
NOTE: Italicized text within this document has been taken verbatim from the Protocol.
PPD


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
APPENDICES ...........................................................................................................................4
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Design .............................................................................................................5
2.2. Study Objectives .......................................................................................................9
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................9
4. HYPOTHESES AND DECISION RULES.........................................................................10
4.1. Statistical Hypotheses .............................................................................................10
4.2. Statistical Decision Rules........................................................................................10
5. ANALYSIS SETS ...............................................................................................................10
5.1. Pharmacokinetic (PK) Analysis Set ........................................................................10
5.1.1. Concentration Analysis Set.........................................................................10
5.1.2. Parameter Analysis Set...............................................................................10
5.2. Pharmacodynamic Analysis Set..............................................................................10
5.3. Safety Analysis Set..................................................................................................10
5.4. Other Analysis Sets .................................................................................................10
5.5. Treatment Misallocations........................................................................................10
5.6. Protocol Deviations.................................................................................................11
5.6.1. Deviations Assessed Prior to Randomization.............................................11
5.6.2. Deviations Assessed Post-Randomization..................................................11
6. ENDPOINTS AND COVARIATES ...................................................................................11
6.1. Efficacy Endpoint(s) ...............................................................................................11
6.2. Safety Endpoints .....................................................................................................11
6.3. Other Endpoints.......................................................................................................12
6.3.1. PK Endpoints..............................................................................................12
6.3.2. PD Endpoints..............................................................................................12
6.4. Covariates................................................................................................................12
7. HANDLING OF MISSING VALUES ................................................................................12


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7.1. Concentrations Below the Limit of Quantification.................................................13
7.2. Deviations, Missing Concentrations and Anomalous Values .................................13
7.3. Pharmacokinetic Parameters ...................................................................................13
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................13
8.1. Statistical Methods ..................................................................................................13
8.2. Statistical Analyses .................................................................................................14
8.3. Safety Analysis........................................................................................................16
8.3.1. Treatment and Disposition of Participants .................................................16
8.3.2. Demographic and Clinical Examination Data............................................16
8.3.3. Discontinuation(s).......................................................................................16
8.3.4. Adverse Events ...........................................................................................17
8.3.5. Laboratory Data..........................................................................................17
8.3.6. Vital Signs Data..........................................................................................17
8.3.7. ECG Data....................................................................................................17
8.3.8. Physical Examination .................................................................................17
8.3.9. Other Safety Data .......................................................................................17
8.3.10. Concomitant Treatments...........................................................................18
8.3.11. Screening and Other Special Purpose Data ..............................................18
9. REFERENCES ....................................................................................................................19
10. APPENDICES ...................................................................................................................20
LIST OF TABLES
Table 1.
Renal Function Categories by eGFR Ranges .............................................5
Table 2.
Noncompartmental PK Parameters...........................................................12
Table 3.
PK Parameters to be Summarized Descriptively by Group......................15
APPENDICES
Appendix 1. SAS CODE FOR ANALYSES...........................................................................20


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PFIZER CONFIDENTIAL
1. AMENDMENTS FROM PREVIOUS VERSION(S) 
None.
2. INTRODUCTION
PF-06700841 is a potent tyrosine kinase 2 (TYK2)/Janus kinase (JAK) 1 inhibitior that is
currently being developed for the treatment of patients with inflammatory diseases, including
systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), psoriasis (PsO), alopecia
areata (AA), vitiligo, inflammatory bowel disease (IBD), hidradenitis suppurativa (HS) and
atopic dermatitis (AD).
PF-06700841 is intended for chronic use in patients, some of whom may have some degree of 
impaired renal function. Therefore, the purpose of this study is to characterize the effect of 
renal impairment on the plasma PK of PF-06700841. Findings from this study will be used 
to develop dosing recommendations so that the dose and/or dosing interval may be adjusted 
appropriately in the presence of renal disease.
2.1. Study Design
This is a Phase 1, non-randomized, open-label, single-dose, parallel-cohort study to
investigate the effect of renal impairment on the plasma PK, safety and tolerability of
PF-06700841 after single oral dose of 30 mg.  A staged approach, as outlined in detail 
below, will be followed in the study. Participants will be selected and categorized into 
normal renal function or renal impairment groups based on their estimated glomerular 
filtration rate (eGFR) as shown in Table 1.
Table 1.
Renal Function Categories by eGFR Ranges
Cohort
Renal Impairment a
Estimated eGFR b (mL/min))
Number of Participants
1
Severe renal impairment
<30 and not requiring dialysis
8
2
Normal renal function
≥90
8
3
Moderate renal impairment
≥30 to <60
8
4
Mild renal impairment
60 – 89
8
a.
Stages of renal impairment are based on Kidney Disease Outcomes Quality Initiative (KDOQI) 
Clinical Practice Guidelines for Chronic Kidney Disease (CKD).1
b.
Estimate of eGFR based on Modification of Diet in Renal Disease (MDRD) formula. The average of 
the 2 screening eGFR value will be used for group assignment: 
•
Step 1: eGFR (mL/min/1.73 m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if 
African American) where Scr, std denotes serum creatinine measured with a standardized assay.
•
Step 2: Convert the MDRD-derived, body surface area (BSA)-adjusted eGFR obtained above to 
absolute eGFR (mL/min) for eligibility assessment using the following equation: eGFR (mL/min) 
= eGFR (mL/min/1.73 m2) × participant’s BSA where BSA is calculated as BSA= (Weight0.425 h
Height0.725) × 0.007184.


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Part 1: A total of approximately 16 participants will be enrolled in Part 1; approximately
8 participants with severe renal impairment (Cohort 1) and approximately 8 with normal
renal function (Cohort 2) to ensure at least 6 evaluable participants in each group.  
Participants from the severe renal impairment group will be recruited first. The
demographics will be pooled across study sites to determine an average value for age and
weight in the severe impairment group. Subsequently, the healthy participants will be
recruited later such that each participant’s age is within ±10 years and weight is within
±15 kg of the mean of severe renal impairment group. An attempt will be made to maintain a
similar male/female ratio composition between groups. Care will be taken when recruiting
the healthy participants such that the entire group is not of substantially different age or of
substantially different body weight than the severely renally impaired participants. Approval
from the sponsor must be obtained before proceeding with dosing healthy participants with
normal renal function.
If there are participants who withdraw or discontinue treatment from the normal or severe
renal impairment groups and who are considered to be non-evaluable with respect to the
primary PK objective, additional participants can be enrolled at the discretion of the 
sponsor.
Criteria to proceed to Part 2: After statistical evaluation of results from Part 1 (see- study 
protocol Section 9.4), Part 2 will be conducted if the point estimate of PF-06700841 or M1 
area under the concentration-time curve from time 0 to infinity (AUCinf) geometric mean 
ratio (GMR) for the severe renal impairment group (compared to the normal group as 
control) is ≥1.5. If this criterion is not met, the study will stop after Part 1.
Part 2: Based on whether the decision criterion to proceed to Part 2 is met, approximately
8 participants each with moderate (Cohort 3) and mild (Cohort 4) renal impairment will be
enrolled to ensure at least 6 evaluable participants in each group. As in Part 1, renal
impairment classification will be based on eGFR. Healthy participants will not be enrolled 
in Part 2. Healthy participants from Part 1 will be used as the control group for the 
moderate and mild impairment participants.
When recruiting the Part 2 participants, attempts to match the entire group to the 
participants in Part 1 with respect to age, gender and body weight will be made. Other 
demographics, such as race and ethnicity, may be considered for matching the Part 1 and 
Part 2 populations when possible. Statistical considerations to account for any differences in 
demographics are detailed in study protocol Section 9.4.
As in Part 1, if there are participants who withdraw or discontinue treatment from the
moderate or mild impairment group and who are considered to be non-evaluable with 
respect to the primary PK objective, additional participants can be enrolled at the discretion 
of the sponsor.


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For both Parts 1 and 2: All participants in both normal and renal impairment groups will
provide informed consent and undergo Screening evaluations to determine their eligibility.  
Participant screening for participation in this study will consist of 2 CRU outpatient visits 
not more than 14 days apart (but at least 3 days apart), with the 1st screening visit occurring
within 28 days prior to administration of investigational product. Each participant will be
admitted to the research unit on Day -1 (at least 12 hours prior to the dosing of 
PF-06700841 on Day 1). An eGFR value for group placement (provided stable renal 
function is still demonstrated) will be obtained by the average of the 2 screening values 
(using the Modification of Diet in Renal Disease [MDRD] equation). If the renal function 
stability criterion is met but the renal function classification category changes between 
Screening Visit 1(S1) eGFR and the average of the S1 and Screening Visit 2 (S2) eGFRs, the 
eGFR measurement at Day -1 will also be used to determine the appropriate group 
classification category using an average of all 3 eGFR values, to determine whether the 
participant will be eligible for enrollment.
All procedures and their timelines follow the Study Protocol’ Schedule of Activities.
Calculation of eGFR:
The following MDRD equation will be used to calculate eGFR (Scr, std denotes serum
creatinine measured with a standardized assay for serum creatinine):
eGFR (mL/min/1.73m2) = 175 h (Scr, std)-1.154 h (Age)-0.203 h (0.742 if female) h
                                       (1.212 if African American)
Note that the value of eGFR, which is directly obtained from the laboratory or calculated
using the equation above, is generally normalized to an average body size of 1.73 m2 for
diagnosis, prognosis and treatment of renal disease. In terms of clearance of renally filtered
drugs (including secreted drugs), renal elimination capacity is related to absolute 
glomerular filtration rate (GFR) in mL/min. To use the MDRD-derived, body surface area
(BSA)-adjusted value of eGFR to obtain absolute glomerular filtration rate (GFR) (mL/min)
for renal disease classification or participant assignment into different renal disease groups,
this value should be multiplied by the individual participant’s BSA (ie, measured
BSA/1.73 m2). The BSA of an individual can be calculated by the following formula as
described below:
BSA = (Weight0.425 h Height0.725) × 0.007184
In summary, GFR in mL/min calculated as below will be used for renal impairment group
placement:
Step 1: Obtain the MDRD-derived eGFR:
•
eGFR (mL/min/1.73 m2) = 175 × (Scr, std)-1.154 × (Age)-0.203 × (0.742 if female) × 
(1.212 if African American) where Scr, std denotes serum creatinine measured with a 
standardized assay.


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Step 2: Convert the MDRD-derived, BSA-adjusted eGFR obtained above to absolute GFR 
(mL/min) for eligibility assessment using the following equation:
•
eGFR (mL/min) = eGFR (mL/min/1.73 m2) × participant’s BSA where BSA is calculated as 
BSA = (Weight0.425 h Height0.725) × 0.007184.
Creatinine clearance (CLCR) will also be estimated from a spot serum creatinine 
measurement using the following Cockcroft-Gault (C-G) equation:
CLCR (mL/min) = (140 – age [years]) × total body weight (kg) × (0.85 for females) ÷                                    
(72 × serum creatinine (mg/dL))
Note that eGFR calculated by the MDRD equation will be used for categorization of degrees
of renal impairment. Nevertheless, renal function will be estimated using both C-G and
MDRD equations in this study and dose recommendations will be made using both C-G and
MDRD equations.
To be enrolled into the study, participant must demonstrate stable renal function, with ≤25%
change based upon screening S1 eGFR and screening S2 eGFR (calculated by the MDRD 
equation). The S2 eGFR assessment should be performed between 3 to 14 days after the S1 
eGFR assessment. The average of these 2 eGFR values will be used for group placement 
based on the renal function classification category.
•
If the renal function stability criterion is met and the renal function classification 
category remains the same between S1 eGFR and the average of the S1 and S2 
eGFRs, participant will be eligible for enrollment.
•
If the renal function stability criterion is not met, participant will be screen failed.
•
If the renal function stability criterion is met but the renal function classification 
category changes between S1 eGFR and the average of the S1 and S2 eGFRs, the 
eGFR measurement at Day -1 will also be used to determine the appropriate group 
classification category using an average of all 3 eGFR values, to determine whether 
the participant will be eligible for enrollment.
In case of screen failure related to eGFR stability and/or change in the renal function
classification category, participant may be re-screened once after a 30-day period, provided
that the initial screen failure is not due to an Inclusion/Exclusion criterion that results in
permanent disqualification from enrollment (eg, medical history). This can be done only
with sponsor’s approval.


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Please see below table regarding demonstration of stable renal function:
Renal function Measurement
eGFR (mL/min)
Criterion for stability
S1
G1
S2 (Within 3 to 14 days after S1)
G2
∆=|G2-G1|×100/G1a
If ∆≤  25%; stable
If ∆>25%; not stable
Abbreviations: S1= Screening Visit 1; S2= Screening Visit 2.
a Parenthesis of | | represents absolute values.
2.2. Study Objectives
Primary:
•
Part 1: To evaluate the effect of severe renal impairment on the PK of PF-06700841 
and M1, a major metabolite of PF-06700841, following single oral dose 
administration.
•
Part 2 (if applicable): To evaluate the effect of moderate and mild renal impairment 
on the PK of PF-06700841 and M1 following single oral dose administration.
Secondary:
•
To evaluate the safety and tolerability of single oral dose of PF-06700841 in
participants with renal impairment and in healthy participants with normal renal
function.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
No formal interim analysis will be conducted for this study. The data will be reviewed after 
completion of Part 1 in order to determine whether Part 2 will proceed.  Final analysis will 
follow the official database release.  As this will be an open, nonrandomized study, there is 
no formal unblinding.
CCI


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4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
No hypotheses are required.
4.2. Statistical Decision Rules
No decision rules are required.
5. ANALYSIS SETS
5.1. Pharmacokinetic (PK) Analysis Set
5.1.1. Concentration Analysis Set
The PK concentration population is defined as all participants assigned to investigational 
product and treated who have at least 1 concentration measured.
5.1.2. Parameter Analysis Set
The PK parameter analysis population is defined as all participants assigned to
investigational product and treated who have at least 1 of the PK parameters of primary 
interest measured.
5.2. Pharmacodynamic Analysis Set
None.
5.3. Safety Analysis Set
All assigned to investigational product and who take at least 1 dose of investigational 
product.
5.4. Other Analysis Sets
None.
5.5. Treatment Misallocations 
All analyses will be performed on an “as-treated” basis and will not include data from 
participants who are randomized but not treated.
If a participant takes a treatment that is not consistent with the treatment they are randomized 
to, for example takes a treatment out of sequence or takes the same treatment twice, then they 
will be reported under the treatment that they actually receive for all safety, PK and 
pharmacodynamic analyses, where applicable.


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5.6. Protocol Deviations
Participants who experience events that may affect their PK profile (eg, lack of compliance 
with dosing) may be excluded from the PK analysis.  At the discretion of the 
pharmacokineticist a concentration value may also be excluded if the deviation in sampling 
time is of sufficient concern or if the concentration is anomalous for any other reason.
A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure.
5.6.1. Deviations Assessed Prior to Randomization
At Screening, the investigator will assess participants against the inclusion and exclusion 
criteria as set out in Sections 5.1 and 5.2 of the protocol.
5.6.2. Deviations Assessed Post-Randomization
A full list of protocol deviations for the study report will be compiled prior to database 
closure.  Any significant deviation from the protocol will be reviewed prior to database 
closure and a decision taken regarding evaluation for each analysis population.
6. ENDPOINTS AND COVARIATES
6.1. Efficacy Endpoint(s)
None.
6.2. Safety Endpoints
Any events occurring following start of treatment or increasing in severity will be counted as 
treatment emergent.
The following data are considered in standard safety summaries (see protocol for collection 
days and list of parameters):

adverse events,

laboratory data,

vital signs data,

ECG results,

Physical Examination.


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6.3. Other Endpoints
6.3.1. PK Endpoints
Blood and urine samples for PK analysis of PF- 06700841 and M1 will be taken according to 
the Schedule of Activities given in the protocol.
The following PK parameters will be calculated for PF- 06700841 and M1 (if possible) from 
the concentration-time data using standard non compartmental methods:
Table 2.
Noncompartmental PK Parameters
Matrix
PK 
Parameter
Analysis 
Scale
PF-06700841
M1
Plasma
AUCinf*
ln
A, D
A, D
AUC72
ln
A, D
A, D
Cmax
ln
A, D
A, D
Urine
CLR
ln
A, D
A, D
Ae72
R
D
D
Ae72(%)
R
D
D
Key:
A=analyzed using statistical model, D=displayed with descriptive statistics, ln=natural-log 
transformed, R=raw (untransformed), *=if data permits, 
•
Urine samples will be analyzed only if it is determined by the study team that there is a need to do 
so based on the review of plasma PK results for PF-06700841 and M1 (as per study protocol 
Section 8.5.2).
6.3.2. PD Endpoints
None.
6.4. Covariates
None.
7. HANDLING OF MISSING VALUES
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.
CCI
CCI
CCI


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7.1. Concentrations Below the Limit of Quantification
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero.  (In listings BLQ values will be reported as “<LLQ”, where LLQ 
will be replaced with the value for the lower limit of quantification).
7.2. Deviations, Missing Concentrations and Anomalous Values
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if 1 of the following cases is true:
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample),
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
7.3. Pharmacokinetic Parameters
Actual PK sampling times will be used in the derivation of PK parameters.
If a PK parameter cannot be derived from a participant’s concentration data, the parameter 
will be coded as NC (i.e. not calculated). (Note that NC values will not be generated beyond 
the day that a subject discontinues.)
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular renal function group with ≥3 evaluable measurements.  For 
statistical analyses (i.e. analysis of variance), PK parameters coded as NC will also be set to 
missing; and analyses will not be performed for a particular parameter if more than 50% of 
the data are NC.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to an unexpected event such as vomiting before all the compound is adequately absorbed in 
the body), this will be footnoted in summary tables and will not be included in the calculation 
of summary statistics or statistical analyses.
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
8.1. Statistical Methods
Part 1, the effect of the severe renal impairment on PK parameters will be assessed by 
constructing 90% confidence intervals around the estimated difference between the severe 
renal impairment and the normal renal function using a one-way ANOVA model based on 
natural log transformed data.


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Following Part 2 (if conducted), the same ANOVA analysis will be performed using data
from the mild and moderate renal impairment groups.
Part 2 may be conducted if either PF-06700841 or M1 AUCinf GMR for severe renal
impairment group compared to normal group is ≥1.5 in Part 1.
The relationship between PK parameters 
 or renal clearance [CLr], 
) and renal 
function will be determined by a linear regression model for PF-06700841 and M1, if Part 2 
is conducted, and for the PF-06700841.
8.2. Statistical Analyses
Part 1
Analysis of variance (ANOVA) will be used to compare the natural log transformed AUCinf
and Cmax for PF-06700841 and M1 between normal renal function group (Reference) and the
severe impaired renal function group (Test). Estimates of the adjusted mean differences
(Test-Reference) and corresponding 90% confidence intervals (CIs) will be obtained from
the model. The adjusted mean differences and 90% CIs for the differences will be
exponentiated to provide estimates of the ratio of the adjusted geometric means
(Test/Reference) and 90% CIs for the ratios.
Part 2
Part 2 may be conducted if either PF-06700841 or M1 AUCinf GMR for severe renal
impairment group compared to normal group is ≥1.5 in Part 1.
ANOVA will be used to compare the natural log transformed AUCinf and Cmax for
PF-06700841 and M1 between normal renal function group (Reference) and the moderate
and mild impaired renal function groups (Test). Estimates of the adjusted mean differences
(Test-Reference) and corresponding 90% CIs will be obtained from the model. The adjusted
mean differences and 90% CIs for the differences will be exponentiated to provide estimates 
of the ratio of the adjusted geometric means (Test/Reference) and 90% CIs for the ratios. If 
substantial differences in demographic characteristics between healthy and impaired 
participants are observed, weight and age may be explored as covariates.
If Part 2 is executed and data for normal, mild, moderate and severe impairment groups are
available, additional analysis will be performed to assess relationship between appropriate
PK parameters and renal function.
Linear regression will be used to analyze the potential relationship between appropriate PK
parameters (
 or renal clearance [CLr], 
) and renal function (eGFR). 
Estimates of the slope and, intercept, together with their precision (90% CI), and the 
coefficient of determination will be obtained from the model.
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Plots of PK parameters (
 or CLr,
) versus renal function (eGFR) will be
constructed. A regression line and 90% confidence region for the PK parameters and eGFR
will be included if appropriate. Vertical lines for the renal function group cut-off values will
also be presented on the plots. 
Residuals from the models will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals but these will not be included in the clinical study report. If there are major 
deviations from normality or outliers then the effect of these on the conclusions will be 
investigated through alternative transformations and/or analyses excluding outliers.  
Justification for any alternative to the planned analysis will be given in the report of the 
study.
The following PK parameters will be summarized by renal function group:
Table 3.
PK Parameters to be Summarized Descriptively by Group
Parameter
Summary Statistics
AUCinf, 
AUC72, Cmax, 
CLR, 
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum, geometric mean and geometric cv%.
 Ae72
and Ae72%
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum.
Box and whisker plots for individual participant parameters (AUCinf, 
 AUC72 and 
Cmax) will be constructed by renal function group and overlaid with geometric means.
Supporting data from the estimation of 
 and AUCinf will be listed by analyte and group:
terminal phase rate constant (kel); goodness of fit statistic from the log-linear regression (r2); 
the percent of AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of 
time points used in the estimation of kel. This data may be included in the clinical study 
report.
Presentations for PF-06700841 and M1 concentrations will include:
•
A listing of all concentrations sorted by renal function group (present in heading), 
subject ID and nominal time postdose.  The concentration listing will also include the 
actual times.  Deviations from the nominal time will be given in a separate listing.
•
A summary of concentrations by renal function group and nominal time postdose, 
where the set of statistics will include n, mean, median, standard deviation, 
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coefficient of variation (cv), minimum, maximum and the number of concentrations 
above the lower limit of quantification.

Median concentrations time plots (on both linear and semi-log scales) against 
nominal time postdose by renal function group (all renal function groups on the same 
plot per scale, based on the summary of concentrations by renal function group and 
time postdose).

Mean concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose by renal function group (all renal function groups on the same plot per 
scale, based on the summary of concentrations by renal function group and time 
postdose).

Individual concentration time plots by renal function group (on both linear and semi-
log scales) against actual time postdose (there will be separate spaghetti plots for each 
renal function group per scale).

A listing of all urine concentration interval sorted by renal function group (present in 
heading), subject ID and nominal collection duration postdose.
For summary statistics, median and mean plots by sampling time, the nominal PK sampling 
time will be used, for individual subject plots by time, the actual PK sampling time will be 
used.
8.3. Safety Analysis
A set of summary tables split by renal function group will be produced to evaluate any 
potential risk associated with the safety and toleration of administering PF-06700841.
8.3.1. Treatment and Disposition of Participants
Data will be reported in accordance with the sponsor reporting standards.
8.3.2. Demographic and Clinical Examination Data
Demographic data will be summarized by sex at birth and ‘All Participants’ in accordance 
with the sponsor reporting standards.
8.3.3. Discontinuation(s)
Participant discontinuations, temporary discontinuations due to adverse events will be 
detailed and summarized by renal function group.
Data will be reported in accordance with the sponsor reporting standards.


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8.3.4. Adverse Events
Any events occurring following start of treatment or increasing in severity after the start of 
the treatment will be counted as treatment emergent.
Adverse events will be reported in accordance with the sponsor reporting standards by renal
function group.
8.3.5. Laboratory Data
Laboratory data will be summarized accordance with the sponsor reporting standards.
For laboratory parameters which are collected only at Screening for inclusion/exclusion
criteria, data will not be captured for inclusion into the study database and therefore will not
be listed or summarized.
Baseline is defined as the last planned predose measurement taken on Day -1.
8.3.6. Vital Signs Data
Supine measurements of BP, pulse rate, and oral temperature will be taken at times detailed 
in the Schedule of Activities given in the protocol.
Vital Signs will be assessed against the criteria specified in the sponsor reporting standards.
Baseline is defined as the last planned predose measurement taken on Day 1.
These data will be listed and summarized in accordance with the sponsor reporting standards.
8.3.7. ECG Data
ECG data will be taken at times detailed in the Schedule of Activities given in the protocol.
Baseline is defined as the last planned predose measurement taken on Day 1.
These data will be listed and summarized in accordance with the sponsor reporting standards.
8.3.8. Physical Examination
Physical examination data will be taken at times detailed in the Schedule of Activities given 
in the protocol.
These data will be listed and summarized in accordance with the sponsor reporting standards.
8.3.9. Other Safety Data
None.


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8.3.10. Concomitant Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the 
listings.
8.3.11. Screening and Other Special Purpose Data
Prior medication(s) and non-drug treatment(s), HIV, HBsAg, HBcAb, HCVAb, urine drug 
screen, urine or serum pregnancy test (WOCBP only), Illegal drug/tobacco/alcohol use will 
be obtained at Screening.
These data will not be brought in-house, and therefore will not be listed.


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9. REFERENCES
1.
FDA Guidance for Industry – Pharmacokinetics in Patients with Impaired Renal 
Function - Study Design, Data Analysis, and Impact on Dosing and Labeling.  05/98.


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10. APPENDICES
Appendix 1. SAS CODE FOR ANALYSES
For Part 1:
An example of the PROC MIXED code is provided below:
proc mixed data = tab.pk covtest alpha=0.1;
class group;
model l&var = group / S covb alpha=0.1 CL DDFM=KR;
repeated/type=un subject=subjid group=group R;
lsmeans group;
estimate 'Severe vs Normal'
group -1  1;
ods output lsmeans = lsmeans&var;
ods output solutionf = solution&var;
run;
/* Letter assignments for group within the estimate statement above are as follows;
A = Normal (Reference), B = Severe (Test);*/;
For Part 2:
proc mixed data = tab.pk covtest alpha=0.1;
class group;
model l&var = group / S covb alpha=0.1 CL DDFM=KR;
repeated/type=un subject=subjid group=group R;
lsmeans group;
estimate 'Mild vs Normal' group -1 1 0;
estimate 'Moderate vs Normal' group -1 0 1;
ods output lsmeans = lsmeans&var;
ods output solutionf = solution&var;
run;
/* Letter assignments for group within the estimate statement above are as follows;
A = Normal (Reference), C = Moderate (Test), D = Mild (Test);
Severe group is not included */;


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An example of the PROC REG code is provided below:
proc reg data=tab.pk;
model l&var=clcr/clb alpha=0.1;
ods output ParameterEstimates = param&var;
ods output FitStatistics = fit&var;
ods output ANOVA = reg&var;
run;
Note: Similar code will be used for regression analysis with respect to 
and eGFR.
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