Clinical trial NCT04866225
Conditions: Healthy Participants
Keywords: ADME
Sponsor: Pfizer
Start date: 2021-05-11; Completion date: 2021-08-06
Enrollment: 6 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This study is a Phase 1, open-label, non-randomized, 2-period, fixed-sequence, single-dose study of PF-06865571 in healthy male participants to characterize the ADME properties of \[14C\]PF-06865571 following oral administration; and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-06865571 following oral administration of unlabeled PF-06865571 and IV administration of \[14C\]PF-06865571.

Detailed description:

Arms: arm 1: One arm of healthy male participants administered a single oral dose of \[14C\]PF-06865571; followed by a single dose of unlabeled PF-06865571, and IV administration of \[14C\]PF-06865571 three hours later.
Interventions: intervention 1: Oral [14C]PF-06865571 intervention 2: Oral PF-06865571 intervention 3: IV [14C]PF-06865571
Intervention descriptions: intervention 1: Oral radiolabeled PF-06865571 intervention 2: Oral PF-06865571 intervention 3: IV radiolabeled PF-06865571

Protocol documents:
Prot_000.pdf: 
PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 1
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY IN HEALTHY 
ADULT MALE PARTICIPANTS TO ASSESS THE EXTENT OF EXCRETION, 
ABSOLUTE BIOAVAILABILITY, FRACTION ABSORBED, AND 
PHARMACOKINETICS OF [14C]PF-06865571 USING A 14C-MICROTRACER 
APPROACH
Study Intervention Number:
PF-06865571
Study Intervention Name:
N/A
US IND Number:
EudraCT Number:
N/A
Protocol Number:
C2541007
Phase:
Phase 1
Short Title: A Study in Healthy Adult Male Participants to Assess ADME Properties of
[14C]PF-06865571
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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PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 2
Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
11 Dec 2020
N/A


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 3
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
LIST OF FIGURES ...................................................................................................................7
1. PROTOCOL SUMMARY.....................................................................................................8
1.1. Synopsis ....................................................................................................................8
1.2. Schema ......................................................................................................................8
1.3. Schedule of Activities ...............................................................................................9
2. INTRODUCTION ...............................................................................................................15
2.1. Study Rationale .......................................................................................................15
2.2. Background .............................................................................................................15
2.2.1. Nonclinical Pharmacokinetics and Metabolism .........................................15
2.2.2. Clinical Overview.......................................................................................16
2.2.2.1. Summary of Clinical Safety......................................................16
2.2.2.2. Summary of Clinical Pharmacology .........................................16
2.3. Benefit/Risk Assessment.........................................................................................17
2.3.1. Risk Assessment.........................................................................................18
2.3.2. Benefit Assessment.....................................................................................20
2.3.3. Overall Benefit/Risk Conclusion................................................................20
3. OBJECTIVES AND ENDPOINTS.....................................................................................20
4. STUDY DESIGN.................................................................................................................21
4.1. Overall Design.........................................................................................................21
4.2. Scientific Rationale for Study Design.....................................................................22
4.3. Justification for Dose ..............................................................................................23
4.4. End of Study Definition ..........................................................................................24
5. STUDY POPULATION......................................................................................................24
5.1. Inclusion Criteria.....................................................................................................24
5.2. Exclusion Criteria....................................................................................................25
5.3. Lifestyle Considerations..........................................................................................27
5.3.1. Meals and Dietary Restrictions...................................................................27
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................29
5.3.3. Activity .......................................................................................................29


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 4
5.4. Screen Failures ........................................................................................................29
6. STUDY INTERVENTION..................................................................................................29
6.1. Study Intervention(s) Administered........................................................................29
6.1.1. Administration............................................................................................30
6.2. Preparation/Handling/Storage/Accountability ........................................................30
6.2.1. Preparation and Dispensing........................................................................31
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................32
6.3.1. Allocation to Study Intervention ................................................................32
6.4. Study Intervention Compliance...............................................................................32
6.5. Concomitant Therapy..............................................................................................32
6.5.1. Rescue Medicine.........................................................................................33
6.6. Dose Modification...................................................................................................33
6.7. Intervention After the End of the Study..................................................................33
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................33
7.1. Discontinuation of Study Intervention ....................................................................33
7.2. Participant Discontinuation/Withdrawal From the Study.......................................34
7.2.1. Withdrawal of Consent...............................................................................34
7.3. Lost to Follow up ....................................................................................................35
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................35
8.1. Efficacy Assessments..............................................................................................36
8.2. Safety Assessments .................................................................................................36
8.2.1. Physical Examinations................................................................................36
8.2.2. Vital Signs ..................................................................................................37
8.2.3. Electrocardiograms.....................................................................................37
8.2.4. Clinical Safety Laboratory Assessments ....................................................38
8.2.5. COVID-19 Specific Assessments...............................................................39
8.3. Adverse Events and Serious Adverse Events..........................................................39
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......39
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................40
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................40
8.3.2. Method of Detecting AEs and SAEs ..........................................................40


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
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8.3.3. Follow-up of AEs and SAEs.......................................................................40
8.3.4. Regulatory Reporting Requirements for SAEs...........................................41
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................41
8.3.5.1. Exposure During Pregnancy......................................................41
8.3.5.2. Exposure During Breastfeeding ................................................43
8.3.5.3. Occupational Exposure .............................................................43
8.3.6. Cardiovascular and Death Events...............................................................43
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................43
8.3.8. Adverse Events of Special Interest.............................................................43
8.3.8.1. Lack of Efficacy........................................................................44
8.3.9. Medical Device Deficiencies......................................................................44
8.3.10. Medication Errors.....................................................................................44
8.4. Treatment of Overdose............................................................................................44
8.5. Pharmacokinetics ....................................................................................................45
8.5.1. Period 1 Plasma for Analysis of Total 14C and Metabolite 
Profiling/ID......................................................................................................45
8.5.2. Period 2 Plasma for Analysis of [14C]PF-06865571 (After IV
Administration)................................................................................................46
8.5.3. Plasma for Analysis of Unlabeled PF-06865571 (Periods 1 and 2)...........47
8.5.4. Urine for Analysis of Total 14C (Oral and IV) and Metabolite
Profiling/ID......................................................................................................47
8.5.5. Feces for Analysis of Total 14C (Oral and IV) and Metabolite
Profiling/ID......................................................................................................48
8.5.6. Emesis.........................................................................................................48
8.6. Pharmacodynamics..................................................................................................48
8.7. Genetics...................................................................................................................49
8.7.1. Specified Genetics ......................................................................................49
8.7.2. Banked Biospecimens for Genetics............................................................49
8.8. Biomarkers ..............................................................................................................49
8.8.1. Specified Gene Expression (RNA) Research .............................................49
8.8.2. Specified Protein Research.........................................................................49


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 6
8.8.3. Specified Metabolomic Research ...............................................................49
8.8.4. Banked Biospecimens for Biomarkers .......................................................49
8.9. Immunogenicity Assessments.................................................................................50
8.10. Health Economics .................................................................................................50
9. STATISTICAL CONSIDERATIONS ................................................................................50
9.1. Statistical Hypotheses .............................................................................................50
9.2. Sample Size Determination.....................................................................................50
9.3. Analysis Sets ...........................................................................................................50
9.4. Statistical Analyses .................................................................................................51
9.4.1. Primary Endpoint(s)....................................................................................51
9.4.1.1. Extent of Excretion (Period 1) ..................................................51
9.4.1.2. Metabolic Profiling/Identification (Period 1)............................52
9.4.2. Secondary Endpoint(s)................................................................................52
9.4.2.1. Pharmacokinetic Parameters .....................................................52
9.4.3. Tertiary/Exploratory Endpoint(s) ...............................................................55
9.4.3.2. Cumulative Rate of Excretion (Period 1)..................................55
9.4.3.3. Pharmacokinetics Parameters (Unlabeled PF-06865571 -
Period 2) ............................................................................................55
9.4.4. Other Safety Analyses ................................................................................55
9.4.5. Other Analyse(s).........................................................................................56
9.5. Interim Analyses .....................................................................................................56
9.6. Data Monitoring Committee or Other Independent Oversight 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
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PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 7
10.1.4. Data Protection .........................................................................................59
10.1.5. Dissemination of Clinical Study Data ......................................................59
10.1.6. Data Quality Assurance ............................................................................61
10.1.7. Source Documents....................................................................................62
10.1.8. Study and Site Start and Closure ..............................................................62
10.1.9. Publication Policy.....................................................................................63
10.1.10. Sponsor’s Qualified Medical Personnel .................................................64
10.2. Appendix 2: Clinical Laboratory Tests .................................................................65
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................67
10.3.1. Definition of AE .......................................................................................67
10.3.2. Definition of SAE.....................................................................................68
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................69
10.3.4. Reporting of SAEs....................................................................................72
10.4. Appendix 4: Contraceptive Guidance ...................................................................74
10.4.1. Male Participant Reproductive Inclusion Criteria....................................74
10.5. Appendix 5: Genetics............................................................................................75
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........76
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................78
10.8. Appendix 8: Abbreviations ...................................................................................80
11. REFERENCES ..................................................................................................................84
LIST OF TABLES
Table 1.
Protocol-Required Safety Laboratory Assessments .................................65
LIST OF FIGURES
Figure 1.
Two (2)-Period Fixed Sequence Study Design ........................................21


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 8
1. PROTOCOL SUMMARY 
1.1. Synopsis 
Not applicable.
1.2. Schema
Not applicable.


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 9
1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Visit Identifier
Screening
Period 1 (P1) and Period 2 (P2), unless otherwise limited to 1 of these 2 Periodsa
F/U
Phone 
Call
ET
Days Relative to 
Day 1
-42 to -2
-1
1
2
3b
4
5
6
7-21c
≥28 -
35
days 
(P2 
only)
-
Hours After Oral
PF-06865571 Dose
-
-
0
0.5
1
2
3
3.08
3.17
3.25
3.5
3.75
4
6
9
12
16
24
27
36
48
51
72
96
120
144-
504
-
Hours After IV
[14C]PF-06865571 
Dose
(P2 Only)
-3
0
0.08
3
(5 
min)
0.17
(10 
min)
0.25
(15
min)
0.5
(30 
min)
0.75
(45 
min)
1
3
6
9
13
21
24
33
45
48
Informed Consent
X
Inclusion/Exclusion 
Criteria
X
X


















Admission to the 
CRU (P1 only)
X























CRU confinement
X













Xb,c



Xc
Medical/medication 
history (update) 
X
X
Height and Weight
X
Physical 
Examinationd
X
Xe
X
Supine 12-lead 
ECG
X
X
Xe
X
Supine Vital Signs
(Blood Pressure 
and Pulse Rate)
X
X
Xe
X
COVID-19 
questionnairef
X
X


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 10
Visit Identifier
Screening
Period 1 (P1) and Period 2 (P2), unless otherwise limited to 1 of these 2 Periodsa
F/U
Phone 
Call
ET
Days Relative to 
Day 1
-42 to -2
-1
1
2
3b
4
5
6
7-21c
≥28 -
35
days 
(P2 
only)
-
Hours After Oral
PF-06865571 Dose
-
-
0
0.5
1
2
3
3.08
3.17
3.25
3.5
3.75
4
6
9
12
16
24
27
36
48
51
72
96
120
144-
504
-
Hours After IV
[14C]PF-06865571 
Dose
(P2 Only)
-3
0
0.08
3
(5 
min)
0.17
(10 
min)
0.25
(15
min)
0.5
(30 
min)
0.75
(45 
min)
1
3
6
9
13
21
24
33
45
48
COVID-19
temperature checkg
X
X
Xh
→
→→→
→
→
→
→
→
→→→→
→
→
→ →
→
→ 
→
→
→
X
X
Serious and Non-
serious Adverse 
Event Monitoring
X
→
→
→
→→→
→
→
→
→
→
→→→→
→
→
→ →
→
→ 
→
→
→
X
X
X
Standard Mealsi
X
Xi
X
X
X
X
X
X
X
X
X
Oral 300 mg 
[14C]PF-06865571 
Administration
(P1 Only)
X
Oral 300 mg 
PF-06865571 
Administration
(P2 only)
X
IV infusion 100 μg
[14C]PF-06865571 
Administration
(P2 Only)
X
→
→
X
COVID-19 testingk
X
X
 
X
Xk
Emesis Collection 
for Radioactivity 
Measurement, if 
Occurs (P1 Only)
X
→
→→→
→
→
→
→
→
→→→→
→
X
CCI


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 11
Visit Identifier
Screening
Period 1 (P1) and Period 2 (P2), unless otherwise limited to 1 of these 2 Periodsa
F/U
Phone 
Call
ET
Days Relative to 
Day 1
-42 to -2
-1
1
2
3b
4
5
6
7-21c
≥28 -
35
days 
(P2 
only)
-
Hours After Oral
PF-06865571 Dose
-
-
0
0.5
1
2
3
3.08
3.17
3.25
3.5
3.75
4
6
9
12
16
24
27
36
48
51
72
96
120
144-
504
-
Hours After IV
[14C]PF-06865571 
Dose
(P2 Only)
-3
0
0.08
3
(5 
min)
0.17
(10 
min)
0.25
(15
min)
0.5
(30 
min)
0.75
(45 
min)
1
3
6
9
13
21
24
33
45
48
Blood Sample Collection for -
PK of PF-
06865571 
following oral [14C] 
PF-06865571 in P1 
and unlabeled 
PF-06865571 in P2l
X
X
X
X
X
X
X
X
X
X
X
X
Xl
X
X
X
X
Total 
Radioactivitym
(P1 only)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xm
X
Metabolite
profiling/IDm
(P1 only)
X
X
X
X
X
X
X
X
X
X
Xm
X
PK of IV infusion 
[14C]PF-06865571
(P2 Only)
Xn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety laboratory 
X
X
Xe
X
HIV, HBsAg, 
HCVAb
X
Pfizer Genomic 
Prep D1.5 Banked 
Biospecimen
(P1 Only)o
X
Pfizer Prep B1
Banked 
Biospecimen
(P1 Only)o
X


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 12
Visit Identifier
Screening
Period 1 (P1) and Period 2 (P2), unless otherwise limited to 1 of these 2 Periodsa
F/U
Phone 
Call
ET
Days Relative to 
Day 1
-42 to -2
-1
1
2
3b
4
5
6
7-21c
≥28 -
35
days 
(P2 
only)
-
Hours After Oral
PF-06865571 Dose
-
-
0
0.5
1
2
3
3.08
3.17
3.25
3.5
3.75
4
6
9
12
16
24
27
36
48
51
72
96
120
144-
504
-
Hours After IV
[14C]PF-06865571 
Dose
(P2 Only)
-3
0
0.08
3
(5 
min)
0.17
(10 
min)
0.25
(15
min)
0.5
(30 
min)
0.75
(45 
min)
1
3
6
9
13
21
24
33
45
48
Urine Sample collection for -
Spot Collection for 
Urine Drug 
Screening (P1 only)
X
X
Spot Collection for 
Urine Cotinine 
Screening
(P1 only)
X
X
Spot Collection for 
Urinalysis (and 
Microscopy, if 
needed)p
X
X
Xe
X
Total Radioactivity 
and Metabolite 
profiling/IDq
(P1 Only)
Xq
X








X

X

X

X
X
X
Xo
X
Total 
Radioactivityq
(P2 Only)
X






X


X


Xq
Feces Sample collection for -
Total Radioactivity 
and Metabolite IDr
(P1 Only)
Xr
X









X

X

X
X
X
Xr
X
[14C]PF-06865571r
(P2 Only)
Xr








X


Xr
Abbreviations: = ongoing/continuous event; AE = adverse event; COVID-19 = Coronavirus disease 2019; CRU = Clinical Research Unit; ECG = electrocardiogram; ET=early 
termination; F/U=follow-up; HCVAb = hepatitis C antibody; HBsAg = hepatitis B surface antigen; HIV = human immunodeficiency virus; P1 = Period 1; P2 = Period 2; 
PK = pharmacokinetics; SAE = serious adverse event; LC/MS = liquid chromatography tandem mass spectrometry; ET = early termination.


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 13
Visit Identifier
Screening
Period 1 (P1) and Period 2 (P2), unless otherwise limited to 1 of these 2 Periodsa
F/U
Phone 
Call
ET
Days Relative to 
Day 1
-42 to -2
-1
1
2
3b
4
5
6
7-21c
≥28 -
35
days 
(P2 
only)
-
Hours After Oral
PF-06865571 Dose
-
-
0
0.5
1
2
3
3.08
3.17
3.25
3.5
3.75
4
6
9
12
16
24
27
36
48
51
72
96
120
144-
504
-
Hours After IV
[14C]PF-06865571 
Dose
(P2 Only)
-3
0
0.08
3
(5 
min)
0.17
(10 
min)
0.25
(15
min)
0.5
(30 
min)
0.75
(45 
min)
1
3
6
9
13
21
24
33
45
48
Note: Black color denotes oral dose administration and sampling post oral administration and Red color denotes IV dose administration and sampling post IV administration. 
IV samples may optionally be labeled with the corresponding time relative to the oral dose for sample collection; however, PK data for the IV administration will be analyzed 
relative to the start of the IV infusion.
a.
There will be a wash-out period of 8-22 days from drug administration in Period 1 and Period 2.  The day to start Period 2 is dependent on the duration for Period 1 but will 
be at least after all sample collection in Period 1 are complete.
b.
In Period 2, participants will be discharged on Day 3 (ie, 48 hours IV dose administration).
c.
Dosing in Period 2 (as 1 cohort) or Completion of Period 1 (1 participant at a time) when at least 1 of 3 criteria are met: (1) ≥90% of radioactive dose has been recovered in 
urine+feces+emesis (if any); (2) <1% of radioactive dose has been recovered in urine+feces during 24H interval over 2 consecutive days; (3) participant has reached Day 21 
(in Period 1).  At the latest, Period 2, Day -1 would occur on the same day as Period 1, Day 21.
d.
Full physical examination will be conducted at Day -1 (Period 1); otherwise brief physical exam envisioned for findings during previous PE or new/open AEs, at 
Investigator discretion.
e.
Procedures to be completed at time of discharge in Period 2 only.
f.
A site-generated questionnaire checking suspected contact and COVID-19 related symptoms to be completed by participants.
g.
Participant’s body temperature will be checked at least twice daily (approximately 12 hours apart) during the CRU confinement.
h.
The first body temperature check on Day 1 of each period will be performed before PF-06865571 dosing.
i.
Standardized meals to be served at clock times matching approximately –0.5H (see Section 5.3.1), and at 4H and 9-10H relative to oral PF-06865571 dosing.
k.
Testing for COVID-19 pathogen (SARS-CoV-2) by PCR will be performed at each visit to the CRU (Screening and Admission). For participants admitted for residence in 
the CRU, subsequent COVID-19 tests will be performed 2x/week at a minimum.
l.
For Period 2, Plasma PK of PF-06865571 will only be assessed up to 48 hours.
m.
Samples are to be collected up to 120 hours.  Based on emerging data, up to 2 additional samples for total 14C accelerator mass spectrometry (AMS) and metabolite profiling 
between Day 7 and Day 21 of Period 1 completion may be collected.
n.
Sample will be used for sample dilution, if necessary, using matrix matched plasma.  [14C]PF 06865571 concentration will not be determined in this sample.
o.
If not collected on the designated collection day, the banked biospecimen can be collected at the next available time point when biospecimens are being collected in 
conjunction with a participant visit.
CCI


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Visit Identifier
Screening
Period 1 (P1) and Period 2 (P2), unless otherwise limited to 1 of these 2 Periodsa
F/U
Phone 
Call
ET
Days Relative to 
Day 1
-42 to -2
-1
1
2
3b
4
5
6
7-21c
≥28 -
35
days 
(P2 
only)
-
Hours After Oral
PF-06865571 Dose
-
-
0
0.5
1
2
3
3.08
3.17
3.25
3.5
3.75
4
6
9
12
16
24
27
36
48
51
72
96
120
144-
504
-
Hours After IV
[14C]PF-06865571 
Dose
(P2 Only)
-3
0
0.08
3
(5 
min)
0.17
(10 
min)
0.25
(15
min)
0.5
(30 
min)
0.75
(45 
min)
1
3
6
9
13
21
24
33
45
48
p.
Microscopy required only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
q.
“Blank” sample collected within 24H prior to dosing in each period; and over intervals of 0-12H, 12-24H, 24-48H, 48-72H, 72-96H, 96-120H plus each 24H interval, 
relative to oral dosing in Period 1. In Period 2, samples will be collected over 0-12H, 12-24H and 24-48H following administration of IV radiolabeled drug.
r.
“Blank” sample collected within 24H prior to dosing in each period; samples collected over 0-24H, 24-48H, 48-72H, 72-96H, 96-120H plus each 24H interval relative to 
oral dosing in Period 1.  In Period 2, samples will be collected over 0-24H and 24-48H following administration of IV radiolabeled drug.


PF-06865571
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2. INTRODUCTION
PF-06865571 is a diacylglycerol acyltransferase 2 (DGAT2) inhibitor that is currently being 
developed for the treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis.
2.1. Study Rationale 
The purpose of this study is to assess the extent of excretion of PF-06865571 as well as the 
absolute bioavailability, fraction absorbed and pharmacokinetics of PF-06865571 in healthy 
male participants using a 14C microtracer dose approach.
2.2. Background 
Diacylglycerol acyltransferases (DGATs) catalyze the terminal step in triglyceride (TG) 
synthesis; specifically, the esterification of a fatty acid with diacylglycerol (DAG) resulting 
in the formation of TG.1  In mammals, two structurally unrelated DGAT enzymes (DGAT1 
and DGAT2) have been characterized.  DGAT1 is highly expressed in the intestine and plays 
a central role in fat absorption.2  DGAT2 is highly expressed in liver and adipose.3 In 
preclinical models, blockade of hepatic DGAT2 using antisense oligonucleotides results in 
both down-regulation of the expression of multiple genes encoding proteins involved in 
lipogenesis and parallel induction in oxidative pathways.4,5  The net result of these changes is 
a decrease in the levels of hepatic DAG and TG lipid which, in turn, reduces hepatocyte lipid 
burden and decreases hepatic very low density lipoprotein (VLDL) TG secretion.5,6
PF-06865571 is a potent, reversible oral, small molecule DGAT2 inhibitor that is postulated 
to decrease hepatic TG synthesis and hepatic lipid burden in non-alcoholic fatty liver disease 
(NAFLD) and nonalcoholic steatohepatitis (NASH).  Based on observations in nonclinical 
studies conducted, it is hypothesized that DGAT2i will impact both physiological drivers 
contributing to NASH via direct inhibition of liver triglyceride synthesis, as well as adaptive 
responses leading to reduction in hepatic DNL. Following 2 weeks of dosing in participants 
with NAFLD, DGAT2i has been shown to reduce liver fat in a dose-responsive manner.
2.2.1. Nonclinical Pharmacokinetics and Metabolism
Nonclinical studies indicate that PF-06865571 was rapidly absorbed in rat and moderately 
absorbed in monkey with mean oral bioavailability of 31% and 48%, respectively. In vitro, 
PF-06865571 showed high passive permeability, and preliminary studies indicated that 
PF-06865571 was a substrate for multi-drug resistance protein (MDR)1 (also known as 
P-glycoprotein [P-gp]) and mouse breast cancer resistance protein (mBCRP) efflux 
transporters.
PF-06865571 was moderately bound to plasma proteins.  The mean unbound fraction of 
PF-06865571 was 0.464, 0.213, 0.331, 0.419, 0.360, and 0.353 in rat, rabbit, dog, monkey, 
and human plasma, respectively, with PF-06865571 preferentially distributing into plasma 
relative to blood.


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The major primary metabolic pathway identified from preliminary in vitro and in vivo 
metabolite profiling in human is O-de-ethylation with subsequent sulfation and 
glucuronidation. There was no evidence of human unique metabolites. Reaction 
phenotyping studies indicate the total cytochrome P450 (CYP) contribution to PF-06865571 
metabolism was >96%, and CYP3A was the predominant isoform responsible for the 
metabolism of PF-06865571 suggesting a risk of clinical drug-drug interactions (DDI) with 
PF-06865571 as a victim upon co-administration with CYP3A inhibitors or inducers. 
While in vitro data suggest that PF-06865571 has the potential to induce CYP3A4 and 
CYP2B6, in a clinical study (C2541002), there was no dose-response relationship of 
endogenous biomarkers of CYP3A4 induction with increasing repeated doses of 
PF-06865571 up to 1800 mg/day. PF-06865571 also has the potential to inhibit uridine 
diphosphate-glucuronosytransferase (UGT) 1A1, UGT1A9, and UGT2B15 based on in vitro 
data from human liver microsomes. In addition, in vitro evaluations suggest that 
PF-06865571 has the potential to inhibit CYP2C9, intestinal CYP3A, P-gp, breast cancer 
resistance protein (BCRP), organic cation transporter (OCT)1, OCT2, and multidrug and 
toxic compound extrusion transporter (MATE)1 at the highest planned clinical dose in the 
program going forward (ie, 300 mg twice daily [BID]).
2.2.2. Clinical Overview
2.2.2.1. Summary of Clinical Safety
As of the issuance of this protocol, 9 clinical studies with PF-06865571 have been 
completed.  Across these 9 studies, a total of 306 unique participants have been randomized. 
This includes 141 unique healthy adult participants, 18 adults with hepatic impairment, and 
165 adults with NAFLD. Of the 306 participants randomized, 231 (75%) were exposed to 
PF-06865571 - 65 unique participants (28%) to single oral doses of PF 06865571 and an 
additional 166 participants (72%) to repeated, oral, doses of PF-06865571 for up to 6 weeks.
Administration of PF-06865571 alone has been found to be well tolerated with the maximum 
tolerated dose not identified and no adverse drug reactions identified.  Upon administration 
of single oral doses of PF-06865571, across the 300-fold dose range evaluated (ie, 5 to 1500 
mg), TEAEs reported in ≥4 participants across all arms evaluated were headache (12%), and 
diarrhea (7%).
2.2.2.2. Summary of Clinical Pharmacology
Following administration of single oral doses of PF-06865571 under fed conditions in 
C2541001, median time for Cmax (Tmax) ranged from 1.5 to 4 hours across the dose groups.  
Approximate dose-proportional increases in Cmax and AUC24 were observed between the 
5 mg and 1500 mg doses.  Under fed conditions, the mean terminal elimination half-life (t½) 
ranged from 1.5 to 5.2 hours.  At the 1000 mg dose level, exposures under fasted condition 
were approximately 2-fold lower than those in the fed state.  Median PF-06865571 Tmax
occurred earlier in the fasted state, compared to dosing under fed conditions (1 h versus 4 h).  
In addition, the terminal elimination t½ under fasted conditions was more variable than under 
fed conditions.  


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Following repeated administration of oral doses of PF-06865571 under fed conditions in 
C2541002, Cmax values on Days 1, 7 and 14 were observed within a median Tmax range of 1.5 
to 3.0 hours post-dose across the 30 mg - 600 mg Q8H doses. Steady state appeared to have 
been reached by Day 4 based on PF-06865571 median trough plasma concentration-time 
profiles. Following a single dose on Day 1 and at steady state (Days 7 and 14), PF-06865571 
plasma exposure across the 30 mg - 600 mg Q8H doses appeared to increase in a dose 
proportional manner based on geometric mean AUCtau and Cmax values. Mean t½ on Day 14 
ranged from 3.29 hours to 6.92 hours across the 30 mg - 600 mg Q8H doses with longer t½
values observed at higher doses. Minimum drug accumulation was observed following 
multiple dose administration of PF-06865571 Q8H.  Mean accumulation ratios ranged from 
0.950 to 1.33 based on AUCtau values and 0.990 to 1.44 based on Cmax values across all doses 
on both Day 7 and Day 14. The proportion of drug excreted via renal elimination on Day 14 
was low, with less than approximately 2% (mean Aetau% values ranged between 0.696% and 
1.79%) of the dose excreted in urine as unchanged drug over the dosing interval across the 
30 mg - 600 mg Q8H doses.  Mean CLr values ranged between 0.293 to 0.630 L/hr.
2.3. Benefit/Risk Assessment
The current study is the first to administer radiolabeled, nCi doses of [14C]PF-06865571 –
both orally and intravenously. The single doses of PF-06865571 administered in this study 
are not expected to provide any clinical benefit to healthy participants. This study is 
designed primarily to evaluate the ADME properties of PF-06865571 along with absolute 
bioavailability and fractional absorbed following administration in healthy adult males.
As of the issuance of this protocol, no specific human risks have been identified with oral 
administration of PF-06865571; potential risks with PF-06865571 and the current study, are 
summarized in Section 2.3.1.  More detailed information about the known and expected 
benefits and risks and reasonably expected adverse events of PF-06865571 may be found in 
the investigator’s brochure, which is the SRSD for this study. 


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PFIZER CONFIDENTIAL
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s) PF-06865571
First time clinical administration of 
[14C]PF-06865571 – both orally and 
intravenously
Single oral doses up to 1500 mg of PF-
06865571 observed to be well tolerated; single, 
oral dose of PF-06865571 in this study (300 mg) 
represents is 5-fold lower
IV dose of PF-06865571 in this study (100 µg) 
is 15,000-fold lower than the highest oral dose 
previously administered and observed to be well 
tolerated
Microtracer of [14C]PF-06865571 identified for 
this study (300 nCi) is equivalent to 0.75 mrem,
which represents radiation exposure which is 
well below the average dose (in US) per year 
from background radiation sources which is 610 
mrem, and below common acute radiation doses 
(eg, Dental x-ray ~ 1.5 mrem; Transatlantic 
flight ~ 2.5 mrem; Mammogram ~ 72 mrem; 
Full body CT scan ~ 1000 mrem). Additionally, 
the radioactive dose to be administered is 
categorized as the lowest risk category of 1 by 
the ICRP.7
Administration of PF-06865571 will occur in an 
inpatient setting under close supervision
Clear communication via ICD of negligible risk 
with the [14C]PF-06865571 doses administered 
and PF-06865571 IV dose relatively to 
previously administered oral doses
Food effect resulting in change in PF-06865571 
exposure, post oral dose
Clinical data indicate that PF-06865571 
exposure are lower in fasted state than in fed 
state
Study intervention, when administered orally, 
administered with a meal
Exposure in utero
In embryo-fetal development toxicity study in 
rats, lower fetal body weight and skeletal 
anomalies observed at all doses with NOAEL for 
this developmental toxicity not identified
In embryo-fetal developmental toxicity study in 
rabbits, no developmental toxicity observed
Risk of fetal toxicity communicated through 
Section 7 of the PF-06865571 IB (Jan-2020)
Enrollment in this study, considering 
administration of [14C]-study intervention, 
limited to healthy adult males
In males who are sexually active with female 
partner(s) of childbearing potential, use of 
barrier methods not required/mandated given 
safety margins >100-fold – refer to Section 10.4


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Protocol C2541007
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PFIZER CONFIDENTIAL
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Procedures 
Number of serial and parallel procedures to 
ensure near complete collection of each 
radioactive dose administered carry risks for 
non-evaluable data
Duration of washout between the 2 Periods in 
this study are pre-defined but rather guided by 
recovered radioactivity across plasma, urine, 
feces, and when applicable vomitus – which will 
likely vary between participants
Feasibility of parallel evaluation of PK, 
radioactivity, safety is precedented at site 
selected for this study
A priori identified criteria for when dosing can 
occur in Period 2 outlined in Schedule of 
Activities
Clear communication in protocol and to 
participants (via ICD) about the maximum
possible duration of inpatient stay with this stay 
reduced as guided by observed data in study  
Other 
Risk COVID-19 contamination during study

During the pandemic healthy participant could 
be infected with the SARS-COV-2 virus 
through study participation

Leading to increased health risk for study
participants and others involved in study 
conduct, potentially confounding AE with study 
intervention
COVID-19 specific assessments according to 
Schedule of Activities


PF-06865571
Protocol C2541007
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PFIZER CONFIDENTIAL
Page 20
2.3.2. Benefit Assessment
The participants in this study are not expected to obtain any specific benefit beyond 
contributing to the process of developing new therapies in an area of unmet need. They will 
receive close monitoring of their safety via study procedures undertaken (eg, PE, 12-lead 
ECGs, vital signs) which will occur as outlined in this protocol.
2.3.3. Overall Benefit/Risk Conclusion
Based on the safety profile of PF-06865571 observed in clinical studies to date, and the 
measures taken as part of the study designed outlined in this protocol, the risk to the 
participants in this study is deemed to be minimal. The overall benefit:risk profile for 
PF-06865571 supports continued clinical development and the conduct of this study.
3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 

To characterize the extent of excretion of total 
radioactivity in urine and feces following 
administration of a single oral dose of 
[14C]PF-06865571.

Total recovery of radioactivity in urine, feces and total 
excreta (urine + feces) as percentage of total 
radioactive dose administered.

To characterize the metabolic profile and identify 
circulating and excreted metabolites following 
administration of a single oral dose of 
[14C]PF-06865571.

Metabolic profiling/identification and determination 
of relative abundance of [14C]PF-06865571 and the 
metabolites of [14C]PF-06865571 in plasma, urine and 
feces.
Secondary: 
Secondary: 

To quantify plasma PK parameters of PF-06865571
and total radioactivity following administration of a 
single oral dose of [14C]PF-06865571.  

Period 1: AUClast, Cmax, Tmax, and if data permit,
AUCinf and t½ to describe single oral dose of:

Total radioactivity in plasma

PF-06865571 in plasma

To quantify plasma PK parameters of PF-06865571
following administration of a single, IV, microtracer 
of [14C]PF-06865571.

[14C]PF-06865571 (Period 2): AUClast, Cmax, Tmax, and 
if data permit, t½, AUCinf, CL and Vss.

To determine the absolute oral bioavailability (F) of 
PF-06865571 following administration of a single 
oral dose of PF-06865571 compared to a single IV 
microtracer of [14C]PF-06865571. 

Plasma AUCinf of oral unlabeled PF-06865571 and 
IV microtracer of [14C]PF-06865571 in Period 2 only.

To determine the fraction of the dose absorbed (Fa)
following administration of a single oral dose of 
[14C]PF-06865571.

Total urinary radioactivity following oral 
administration of [14C]PF-06865571 in Period 1 and 
IV microtracer administration of [14C]PF-06865571 in 
Period 2.
Tertiary/Exploratory: 
Tertiary/Exploratory: 

To characterize cumulative rate of excretion of total 
radioactivity in urine and feces over time following 
administration of a single oral dose of 
[14C]PF‑06865571.

Cumulative recovery of radioactivity in urine and 
feces, and total excreta (urine + feces) over time as a 
percentage of total radioactive dose administered.


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PFIZER CONFIDENTIAL
Page 21
Objectives
Endpoints
•
To quantify plasma PK parameters of PF-06865571 
in plasma following administration of a single oral 
dose of unlabeled PF-06865571.
•
PF-06865571 plasma (Period 2): AUClast, Cmax, Tmax, 
and if data permit, t½, AUCinf, CL/F, Vz/F.
 
 
 
 
•
To evaluate the safety and tolerability of PF-
06865571, administered as a single oral dose of 
[14C]PF-06865571 or a single oral dose of 
PF-06865571 followed by administration of a single 
IV microtracer of [14C]PF-06865571.
•
AE monitoring, clinical laboratory measurements, 
vital signs and 12-lead ECG.
4. STUDY DESIGN
4.1. Overall Design
This study is a Phase 1, open-label, non-randomized, 2-period, fixed-sequence, single-dose 
study of PF-06865571 in healthy male participants to characterize the ADME properties of
[14C]PF-06865571 following oral administration; and to evaluate the absolute oral 
bioavailability (F) and fraction absorbed (Fa) of PF-06865571 following oral administration 
of unlabeled PF-06865571 and IV administration of [14C]PF-06865571.  
In this study 6 participants will be enrolled to ensure evaluable data is acquired in at least 4 
participants.  Each participant will receive 2 regimens (A and B) in Periods 1 and 2, 
respectively, as outlined in Figure 1.  Participants who withdraw from the study may be 
replaced if the number of evaluable participants is less than 4.
Figure 1.
Two (2)-Period Fixed Sequence Study Design
* Completion of Period 1 (1 participant at a time) when at least 1 of 3 criteria are met: (1) ≥90% of radioactive 
dose has been recovered in urine+feces+emesis (if any); (2) <1% of radioactive dose has been recovered in 
urine+feces during 24H interval over 2 consecutive days; (3) participant has reached Day 21 (in Period 1).
At the latest, Period 2, Day -1 would occur on the same day as Period 1, Day 21.
Washout (8 to 22 days)
\\
Period 1
300 nCi/300 mg PO
Period 2
300 mg PO followed by 
300 nCi/100 μg IV at 
~3 hr post oral dose
Dosing
(D1)
Dosing
(D1)
Plasma, Urine & Feces
(vomitus, as applicable)
Collection in Period 1
Plasma, Urine & Feces
Collection in Period 2
Follow up 
(≥28 to 35 days after 
dosing in Period 2)
Completion of 
Period 1 (D7-21)*
Discharge 
from CRU (D3)
CCI


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Regimen A in Period 1: An oral dose of 300 mg PF-06865571 containing approximately 
300 nCi 14C (ie, radiolabeled PF-06865571) will be administered within approximately 10 
minutes of completion of a standard breakfast (see Sections 5.3.1 and 6.1.1).
Regimen B in Period 2: An oral dose of 300 mg unlabeled PF-06865571 followed at Tmax by 
an IV dose of 300 nCi [14C] in 100 g of PF-06865571 (3 Ci/mg active drug).  The [14C] IV 
dose will be administered as an infusion over approximately 15 minutes.  Oral unlabeled PF-
06865571 will be administered within approximately 10 minutes of completion of a standard 
breakfast (see Sections 5.3.1 and 6.1.1).
Screening will occur within 42 days of the first dose of the investigational product in 
Period 1.  All participants will provide informed consent and undergo screening evaluations 
to determine their eligibility. 
Eligible participants will be admitted to the CRU on Day -1 of Period 1 and scheduled to 
remain in the CRU through the completion of Period 2.  As such, inpatient stay will be for a 
total duration of 12 days (minimum) to 25 days (maximum).  Each participant will have 
1 -follow-up phone call that will occur at least 28 days and up to 35 days following the last 
dose of investigational product to assess for AEs and SAEs. 
In exceptional cases, participants may leave the CRU for personal reasons, at the discretion 
of the investigator, for up to a maximum of 8 hours during Period 1 after Day 7, if the 
participant has completed Period 1 based on the completion criteria defined in Figure 1.  
4.2. Scientific Rationale for Study Design
This study will investigate the ADME of [14C]PF-06865571 and characterize plasma, fecal
and urinary radioactivity and identify any metabolites, if possible, of [14C]PF-06865571 in
male participants (obtained from Periods 1 and 2).  A 2-period design is being used to 
minimize variability and enable within -participant comparison of the urinary excretion of 
radioactivity with both routes for the estimation of Fa.  Only male participants will be 
enrolled to also minimize variability. Only nonsmokers will be enrolled to minimize any 
potential effect on metabolism by smoking. In addition, this study will provide a better 
understanding of the PK disposition of PF-06865571 by obtaining IV clearance and 
delineating the extent of oral absorption (F and Fa), further assisting with BCS classification
assessment for PF-06865571. This information will support the further formulation 
development.  Oral dosing will be administered with a meal as food has been shown to 
significantly increase exposures of PF-06865571 and mimics how PF-06865571 is being 
administered in the clinical program.
Period 2 of this study will enable assessment of F for PF-06865571.  F will provide 
information on the amount of PF-06865571 reaching the systemic circulation.  Determination 
of the Fa (obtained from Periods 1 and 2) will provide information on the fraction of the total 
PF-06865571 dose absorbed, regardless of the fate of that dose after absorption (ie,
metabolism, degradation, etc).  Since F is dependent on Fa, Fg and Fh, characterization of 


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 23
both F and Fa will enable determination of the first pass effect. Therefore, the study will aim 
to characterize both F and Fa.
In order to achieve sufficient bioanalytical sensitivity for the microtracer dose and
differentiate the plasma concentrations resulting from the radiolabeled IV dose and those
resulting from the oral dose, an ultra-sensitive AMS method will be used to quantify plasma 
concentrations of radiolabeled parent drug as well as total 14C derived from the microtracer 
dose based on measurement of 14C.8  PF-06865571 will be considered highly permeable if 
either F or Fa is greater than 0.85 (as per BCS guidance).9
 
The potential risk of exposure to PF-06865571 in a sexual partner of a male participant in 
this study via ejaculate is low, and therefore no contraception (condom) use in male 
participants is warranted.  The calculated safety margin is ≥100-fold between the estimated 
partner exposure due to seminal transfer and the NOAEL for serious manifestations of 
developmental toxicity in nonclinical studies.  The safety margin of 100-fold is based on 
applying a 10-fold safety factor for interspecies extrapolation and a 10-fold safety factor for 
susceptible populations.10
Banked Biospecimens will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
•
14C-labeled PF-06865571 and unlabeled Oral PF-06865571:
A radio-dilute 14C-labeled (300 nCi) 300 mg dose of PF-06865571 for Period 1 and 
unlabeled 300 mg dose in Period 2 were selected as 300 mg is the highest dose being 
evaluated in phase 2 clinical program.  PF-06865571 was found to be well-tolerated with an
acceptable safety profile with single doses up to 1500 mg (C2541001) and repeated doses up 
to 1800 mg/day (C2541002) in healthy participants.  A maximum tolerated dose was not 
identified.  In addition, 300 mg BID dose levels were found to be generally well tolerated 
with an acceptable safety profile over 6-week treatment in NAFLD patients (C3711001).
Based on prior experience in healthy participants and NAFLD patients, a single 300 mg dose 
is expected to have low risk into healthy adult males (see Section 2.2.2). 
Further, single-dose administration is chosen because linear and time-independent PK of   
PF-06865571 have been demonstrated at single or multiple clinical doses, and thus single-
dose PK can predict multiple-dose PK of PF-06865571.
•
14C-labeled PF-06865571 IV microtracer:
The microtracer selection is based on ICH Guidelines.11  A microtracer [14C]PF-06865571 is 
CCI


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 24
planned in this study for both oral (Period 1; 0.001 μCi/mg active dose or 300 nCi/300 mg 
active dose) and IV (Period 2; 3 μCi/mg active dose or 300 nCi/100 μg active dose) 
administration.  The total radioactive dose would be approximately 600 nCi of 14C.  The IV 
dose of 100 g is 0.033% of the oral unlabeled dose of 300 mg.  This dose is sufficient to 
allow quantification of [14C]PF-06865571 based on the sensitivity of the ultrasensitive AMS 
analytical methodology.
4.4. End of Study Definition
A participant is considered to have completed the study if he has completed all phases of the 
study, including the last scheduled procedure shown in the Schedule of Activities (ie, follow-
up phone call).
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 nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male participants, 18 to 60 years of age, inclusive, at the time of signing the ICD.

Refer to Appendix 4 for reproductive criteria for male participants 
(Section 10.4.1).
Type of Participant and Disease Characteristics:
2. Male participants who are overtly healthy as determined by medical evaluation 
including medical history, physical examination, laboratory tests, and cardiac tests.
3. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Participants that are nonsmoking for at least 3 months at the time of signing the ICD.


PF-06865571
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Weight:
5. BMI of 17.5 to 30.4 kg/m2, inclusive; and a total body weight >50 kg (110 lb) with a 
single repeat assessment of BMI and/or body weight permitted on a different day to 
assess eligibility, if needed.
Informed Consent:
6. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
3. History of irregular bowel movements including irritable bowel syndrome or frequent
episodes of diarrhea or constipation, defined by less than 1 bowel movement on 
average per 2 days, or lactose intolerance.
4. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, 
or HCVAb. Hepatitis B vaccination is allowed.
5. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality or other conditions or 
situations related to the COVID-19 pandemic that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for 
the study.

History of SARS-CoV-2 PCR or antibody (eg, IgG, IgM, etc) positive result 
would necessitate accompanying history of asymptomatic state for at least 6 
months prior to screening. 
Prior/Concomitant Therapy:
6. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention with the exception of moderate/potent CYP3A inducers which are 


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prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.  
(Refer to Section 6.5 for additional details).
Prior/Concurrent Clinical Study Experience:
7. Previous administration with an investigational drug within 60 days (or as determined 
by the local requirement) preceding the first dose of study intervention used in this 
study (whichever is longer). 
Diagnostic Assessments:
8. A positive urine drug test.
9. A positive urine cotinine test.
10. 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.
11. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may
affect participant safety or interpretation of study results (eg, baseline QTcF interval
>450 msec, complete LBBB, signs of an acute or indeterminate-age myocardial
infarction, ST-T interval changes suggestive of myocardial ischemia, second- or 
third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF
exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more 
times and the average of the 3 QTc or QRS values should be used to determine the 
participant’s eligibility.  Computer-interpreted ECGs should be overread by a 
physician experienced in reading ECGs before excluding participants.
12. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat test, if deemed necessary:

AST or ALT level ≥1.5 × ULN;

Total bilirubin level ≥ 1.5 × ULN; participants with a history of Gilbert's 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is≤ULN.
13. A positive COVID-19 (SARS-CoV-2) PCR test.
Other Exclusions:
14. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening.  Binge drinking is defined as a pattern of 5 


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or more alcoholic drinks in about 2 hours.  As a general rule, alcohol intake should 
not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 
40% spirit or 3 ounces (90 mL) of wine).
15. Total 14C radioactivity measured in plasma exceeding 11 mBq/mL at screening.
16. From 3 months prior to dosing use of tobacco/nicotine containing products or positive 
urine cotinine test.
17. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing. 
18. History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin 
is used to flush IV catheters used during serial blood collections. 
19. Unwilling or unable to comply with the lifestyle considerations outlined in 
Section 5.3 of this protocol.
20. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members.
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Meals and Dietary Restrictions
After confirmation of eligibility, participants must be reminded that they must:

attempt to abstain from ingestion of indigestible foods (eg, corn, nuts) for 2 days prior 
to dosing (ie, Day -2 and Day -1);

In addition, while inpatient, the meals consumed will follow this restriction to aid 
fecal homogenization. 

refrain from consuming red wine, grapefruit, or grapefruit-related citrus fruits/fruit 
juices (eg, Seville oranges, pomelos) from 7 days prior to the first dose of study 
intervention until collection of the final PK blood sample, in each Period.
While inpatient, the meals consumed are expected to follow the restrictions outlined below 
with participants encouraged to complete each meal. 

Participants must abstain from all food and drink (except water) at least 4 hours prior 
to any safety laboratory evaluations.

Water is permitted until dosing on Day 1 and without restriction beginning 1 hour 
after oral dosing.  


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
Noncaffeinated drinks (except grapefruit or grapefruit-related citrus fruit juices—see 
below) may be consumed with meals and the evening snack.

While inpatient, meals will be standardized as follows –

On Day 1 of each study period, following an overnight fast of at least 10 hours, 
participants will be provided a standard meal approximately 30 minutes prior to 
oral PF-06865571 administration. The breakfast will be consumed over 
approximately a 20-minute interval with PF-06865571 administered within 
approximately 10 minutes of completion of the meal. Participants will be 
encouraged to complete the entire breakfast. The percentage of the meal 
consumed should be documented.

Lunch will be provided approximately 4 hours after dosing of oral PF-06865571.

Dinner will be provided approximately 9 to 10 hours after dosing of oral 
PF-06865571.

An evening snack is permitted.

Standard meals (and an optional evening snack) will be provided at a similar 
clock time to the clock time when these meals are offered on Day 1.

While participants are confined, their total daily nutritional composition should be 
approximately 55% carbohydrate, 30% fat, and 15% protein.  The daily caloric 
intake per participant should not exceed approximately 3200 kcal.

To help assure regularity in bowel movements, nutritional composition should 
contain at least 15 g of fiber per 1000 kcal
This may include consumption of fiber capsules, at a frequency dictated by 
investigator, starting with the evening meal (ie, ~8H post dose) on Day 1, for 
duration of inpatient stay to ensure at least one bowel movement per day; 

If an individual participant has not experienced a bowel movement in the first 24 
hours after dosing, fluid intake should be increased and administration of a mild 
laxative [eg, prune juice or a mild stool softener (eg, docusate)] should be 
implemented, with the goal to facilitate at least one daily bowel movement; 
Despite these measures, if bowel movement does not occur, on Day 2 and 
each subsequent day, consideration should be given to administration of mild 
laxative (eg, milk of magnesia), at the Investigator’s discretion. The use of the 
stool softener / laxative needs to be recorded.


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5.3.2. Caffeine, Alcohol, and Tobacco

Participants will abstain from caffeine-containing products for 24 hours prior to the 
start of dosing until collection of the final PK blood sample in each Period.  

Participants will abstain from alcohol for 24 hours prior (or as specified above for red 
wine) to admission to the CRU and continue abstaining from alcohol until collection 
of the final PK blood sample in each Period.  Participants may undergo an alcohol 
breath test or urine alcohol test at the discretion of the investigator.

Participants will abstain from the use of tobacco- or nicotine-containing products
from 3 months prior to dosing and while confined to the CRU in the study.  
Participants may undergo urine cotinine test at the discretion of the investigator.
5.3.3. Activity

Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to admission and while confined to 
the CRU in the study.  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;
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. Screen failure data are collected and remain as 
source and are not reported to the clinical database.
Individuals who do not meet the criteria for participation in this study (screen failure) cannot
be rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
Unlabeled (ie, non-radiolabeled) PF-06865571 investigational product for oral administration 
will be supplied to the CRU by Pfizer as bulk for extemporaneous preparation.


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Two (2) batches of GMP [14C]PF-06865571 API were prepared with the oral dose being fully 
radio-diluted to the overall specific activity requirements for Period 1 oral dosing and the 
other API lot ready for IV formulation for Period 2 IV dosing. 
[14C]PF-06865571 components for the IV and oral microtracer administration will be 
supplied by Pfizer as bulk API and, where necessary, bulk excipients for the manufacture of 
the [14C] labeled IV solution and oral suspension formulations. The final product 
composition and presentation will be detailed in a separate Technical Agreement (TA) for the 
[14C] labeled IV solution and Extemporaneous Dispensing Records (EDRs) for the [14C] 
labeled and unlabeled oral suspensions.
6.1.1. Administration
In Period 1, [14C]PF-06865571 will be administered as an oral dose. In Period 2, the oral 
unlabeled PF-06865571 will be administered 3 hours before the IV [14C]PF-06865571 dose. 
14C labeled or unlabeled PF-06865571 (300 mg): A standard meal will be provided 
approximately 30 minutes prior to oral PF-06865571 administration in each period.  The 
breakfast will be consumed over approximately a 20-minute interval.  Participants will be 
encouraged to complete the entire breakfast. Qualified investigator site personnel will 
administer labeled or unlabeled PF-06865571 via oral route at approximately 0800 hours 
(plus or minus 2 hours) within approximately 10 minutes of completion of the meal during 
the designated period with water to a total volume of 240 mL according to the site 
administration instructions.
[14C]PF-06865571 (100 g): Ten mL of the 10 g/mL manufactured IV solution of [14C]PF-
06865571 will be administered intravenously (over 15 minutes as a continuous infusion 
through an infusion line using a  calibrated syringe pump or similar).  Preparation and 
administration of [14C]PF-06865571 will be performed by qualified investigator site 
personnel (in accordance with local regulations and laws).  Further details on administration 
are outlined in the site administration instructions. 
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.


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3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken.  The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible.  Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention.  Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the EDR/Roles and Responsibility Matrix.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. See the EDR for storage conditions of the study intervention once reconstituted 
and/or diluted.
7. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record.
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the Roles and Responsibility Matrix.  All destruction 
must be adequately documented.  If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations, institutional policy, and any 
special instructions provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff.  Dispensing is defined as the provision of study intervention, concomitant treatments, 
and accompanying information by qualified staff member(s) to a healthcare provider, 
participant in accordance with this protocol.  Local health authority regulations or 
investigator site guidelines may use alternative terms for these activities.
14C labeled and unlabeled PF-06865571 oral dosing suspensions will be prepared 
extemporaneously at the CRU by 2 trained personnel, at least 1 of whom is a pharmacist.  
Details of dose preparations will be given in separate EDRs.  Prepared doses will be provided 
in unit dose containers and labeled in accordance with Pfizer regulations and the investigator 
site’s labeling requirements.


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[14C]PF-06865571 solution for the IV administration will be manufactured at the clinical 
study site by 2 trained personnel and quality assurance (QA) released prior to administration.  
Details of the dose preparation will be provided in a separate TA.  Prepared doses will be
provided in unit dose containers and labeled in accordance with Pfizer regulations and the 
investigator site’s labeling requirements.  Leftover containers following both oral and IV 
administration, including tubing used for infusion, should be shipped to laboratory for 
assessment of radioactivity, if needed. 
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
Following completion of informed consent at the Screening visit, each participant will be 
assigned a single 8-digit SSID number by the site staff.  The first 4 digits of the SSID will 
reflect the sponsor-assigned site number and the remaining 4 digits will reflect each 
participant’s unique number assigned in chronological order of when informed consent is 
obtained.  Separately, prior to dosing on Day 1, each participant will be assigned a 2-digit 
number to permit analysis of all PK samples.
6.4. Study Intervention Compliance
When the individual dose for a participant is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second qualified member of the study site staff.
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF.  
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention.
The site will complete the required dosage Preparation Record located in the EDR.  The use 
of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system.  The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose.  This may be used in place of the Preparation Record after 
approval from the sponsor and/or designee.
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 study 
intervention with the exception of moderate/potent CYP3A inducers which are prohibited 
within 14 days plus 5 half-lives prior to the first dose of study intervention.  Limited use of 
nonprescription medications that are not believed to affect participant safety or the overall 


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results of the study may be permitted on a case-by-case basis following approval by the 
sponsor. Acetaminophen/paracetamol may be used at doses of ≤1 g/day.  If an individual 
participant has not experienced a bowel movement within 24 hours after dosing of oral 
(Period 1) or IV (Period 2) [14C]PF-06865571, administration of a mild laxative [eg, prune 
juice or a mild stool softener (eg, docusate)] should be implemented, with the goal to 
facilitate at least one daily bowel movement.  Despite these measures, if bowel movement 
does not occur, on Day 2 and each subsequent day, consideration should be given to 
administration of mild laxative (eg, milk of magnesia), at the Investigator’s discretion.  The 
use of the stool softener / laxative should be recorded.
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.  All participants will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 42 days before the first dose of study intervention will be 
documented as a prior treatment.  Treatments taken after the first dose of study intervention
will be documented as concomitant treatments.
6.5.1. Rescue Medicine
There is no rescue therapy to reverse the AEs observed with PF-06865571; standard medical 
supportive care must be provided to manage the AEs. 
6.6. Dose Modification
Not applicable.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following: intolerance of the study drug, SAE, clinically relevant 
laboratory, vital signs or ECG changes.
If study intervention is definitively discontinued, the participant will not remain in the study 
for further evaluation. See the Schedule of Activities for data to be collected at the time of 
discontinuation of study intervention.


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7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the 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 enrolled/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 taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 
and/or posttreatment study follow-up, and entered on the appropriate CRF page.  In the event 
that vital status (whether the participant is alive or dead) is being measured, publicly 


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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 attend a required study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the Schedule of Activities. Protocol
waivers or exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the 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.
Participants will be screened within 42 days prior to administration of the study intervention
to confirm that they meet the study population criteria for the study.  If the time between 
screening and dosing exceeds 42 days as a result of unexpected delays (eg, delayed drug 


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shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.
A participant who qualified for this protocol but did not enroll from an earlier cohort/group
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study.  In 
addition, other clinical assessments or specimen collections, eg, banked biospecimens, may 
be used without repeat collection, as appropriate.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately 
415 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.
8.1. Efficacy Assessments
There are no efficacy assessments included in this protocol.
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 issues.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 


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A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant-reported symptoms.
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation. 
Height and weight will also be measured and recorded as per the 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.  BP should not be taken 
from the arm with a catheter in place for intravenous infusion.  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 (and prior 
to collection of ECG).
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
8.2.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the Schedule of Activities section of this protocol using an 
ECG machine that automatically calculates the heart rate and measures PR, QT, and QTcF
intervals and QRS complex. Alternative lead placement methodology using torso leads (eg,
Mason-Likar) is not recommended given the potential risk of discrepancies with ECGs 
acquired using standard limb lead placement. All scheduled ECGs should be performed after 
the participant has rested quietly for at least 10 minutes in a supine position. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements.  Additional ECG monitoring will occur if a) a 
postdose QTcF interval is increased by ≥60 msec from the baseline and is >450 msec; or b) 
an absolute QTcF value is ≥500 msec for any scheduled ECG.  If either of these conditions 
occurs, then 2 additional ECGs will be collected approximately 2 to 4 minutes apart to 
confirm the original measurement.  If the QTcF values from these repeated ECGs remain 
above the threshold value, then a single ECG must be repeated at least hourly until QTcF


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values from 2 successive ECGs fall below the threshold value that triggered the repeat 
measurement.
If a) a postdose QTcF interval remains ≥60 msec from the baseline and is >450 msec; or b) 
an absolute QTcF value is ≥500 msec for any scheduled ECG for greater than 4 hours (or 
sooner, at the discretion of the investigator); or c) QTcF intervals get progressively longer, 
the participant should undergo continuous ECG monitoring.  
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
or QTcF values are prolonged, as defined above, repeat measurements may not be necessary 
if a qualified medical provider’s interpretation determines that the QTc and QTcF values are 
in the acceptable range.
Additional collection times, or changes to collection times, of ECG will be permitted, as 
necessary, to ensure appropriate collection of safety data.
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.  All protocol-required laboratory 
assessments, as defined in Appendix 2, must be conducted in accordance with the laboratory 
manual and the Schedule of Activities. Unscheduled clinical laboratory measurements may 
be obtained at any time during the study to assess any perceived safety issues.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 calendar days after the last dose of study intervention
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.


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Participants may undergo random urine drug and cotinine testing at the discretion of the 
investigator.  Drug testing conducted prior to dosing must be negative for participants to 
receive study intervention.
8.2.5. COVID-19 Specific Assessments
Participants will be tested for SARS-CoV-2 infection by PCR prior to being admitted to the 
clinic for confinement and subsequent COVID-19 tests will be performed twice weekly while 
confined to the CRU. Additional testing may be required by local regulations or by the 
Principal Investigator.
In addition, as per local practices, site-generated COVID-19 Questionnaire will be expected 
to be completed by the participants each time upon arrival to the clinic – refer to Schedule of 
Activities.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days after the last administration of the study intervention.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.


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If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AE or SAE after the participant has concluded 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has completed the study, and he/she considers the event to be 
reasonably related to the study intervention, the investigator must promptly report the SAE to 
Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
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 


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possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental exposure during pregnancy:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion or skin contact while 
preparing or administering the study drug.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 


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should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 28 calendar 
days after the last dose.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.


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


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8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies
Not Applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of PF-06865571 greater than 1800 mg within a 24-hour time period 
will be considered an overdose.


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Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF-06865571 (whichever 
is longer).  
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis as soon as possible upon identification of 
overdose. 
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 
The samples collected for PK (PF-06865571 concentration), radioactivity (total 14C) and/or 
metabolite profiling assessment must be processed and shipped as indicated in the 
instructions provided to the investigator site to maintain sample integrity. Any deviations 
from the 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.
Samples collected for PK, radioactivity and/or metabolite profiling/ID may also be used to 
evaluate safety or efficacy aspects related to concerns arising during or after the study, for 
metabolite identification and/or evaluation of the bioanalytical method, or for other internal 
exploratory purposes.
Genetic analyses will not be performed on these samples unless consent for this was included 
in the informed consent.  Participant confidentiality will be maintained.
8.5.1. Period 1 Plasma for Analysis of Total 14C and Metabolite Profiling/ID
During Period 1, blood samples of approximately 4 mL for total 14C and 10 mL for 
metabolite profiling/ID, to provide approximately 1.6 mL and 4 mL of plasma, respectively,
will be collected into appropriately labeled tubes containing K2EDTA at times specified in 
the Schedule of Activities.  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.


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The actual times may change, but the number of samples will remain the same.  All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing.  Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF.  Collection of samples more than 10 hours after dose
administration that are obtained ≤1 hour away from the nominal time relative to dosing will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. This protocol deviation window does not apply to 
samples to be collected more than 10 hours after dose administration at outpatient/follow-up 
visits with visit windows.
Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the lab manual.
8.5.2. Period 2 Plasma for Analysis of [14C]PF-06865571 (After IV Administration)
During Period 2, blood samples of approximately 4 mL, to provide approximately 1.6 mL of 
plasma, for PK analysis of radiolabeled [14C]PF-06865571 will be collected into 
appropriately labeled tubes containing K2EDTA at times specified in the Schedule of 
Activities.  Instructions for the collection and handling of biological samples will be provided 
in the laboratory manual or by the sponsor.  The actual date and time (24-hour clock time) of 
each sample will be recorded.
The actual times may change, but the number of samples will remain the same.  All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing.  Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF.  Collection of samples more than 10 hours after dose
administration that are obtained ≤1 hour away from the nominal time relative to dosing will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. This protocol deviation window does not apply to 
samples to be collected more than 10 hours after dose administration at outpatient/follow-up 
visits with visit windows.
Windows defined for times relative to oral dosing are intended to ensure accurate sample 
collection as required for the analysis of both oral and IV data.
Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the lab manual.
Samples collected for measurement of plasma radiolabeled [14C]PF-06865571 concentrations 
will be analyzed using a validated quantitative AMS method after chromatographic 
separation of the parent compound in compliance with applicable SOPs.  


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8.5.3. Plasma for Analysis of Unlabeled PF-06865571 (Periods 1 and 2)
During Periods 1 and 2, blood samples of approximately 3 mL to provide approximately 1.2
mL of plasma for PK analysis of unlabeled PF-06865571 will be collected into appropriately 
labeled tubes containing K2EDTA at times specified  in the Schedule of Activities.  
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor.  The actual date and time (24-hour clock time) of each 
sample will be recorded.
The actual times may change, but the number of samples will remain the same.  All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing.  Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF.  Collection of samples more than 10 hours after dose
administration that are obtained ≤1 hour away from the nominal time relative to dosing will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. This protocol deviation window does not apply to 
samples to be collected more than 10 hours after dose administration at outpatient/follow-up 
visits with visit windows.
Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the lab manual.
Samples collected for measurement of plasma concentrations of PF-06865571 will be 
analyzed using a validated analytical method in compliance with applicable SOPs.
8.5.4. Urine for Analysis of Total 14C (Oral and IV) and Metabolite Profiling/ID
Urine will be collected for determination of total 14C measurement and metabolite 
profiling/ID following oral administration of [14C]PF-06865571 (Period 1 only) and for 
determination of total 14C measurement following IV administration of [14C]PF-06865571 
(Period 2 only), at predose and at post dose intervals as specified in the Schedule of 
Activities.  
Each participant will empty his bladder just prior to dosing on Day 1 and an aliquot from this 
collection will be used as “urine blank”.  During the entire collection period, the urine 
collection container should be refrigerated. At the end of each urine collection period, the 
total volume will be measured and recorded.  All urine aliquots should be collected using a 
new pipette tube for each participant at each time interval.  All urine samples within each 
collection interval will be mixed thoroughly before aliquoting.  
Details regarding the collection volume, processing, storage and shipping of the urine 
samples will be provided in the lab manual.


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8.5.5. Feces for Analysis of Total 14C (Oral and IV) and Metabolite Profiling/ID
Feces will be collected for determination of total 14C measurement and metabolite 
profiling/ID following oral administration of [14C]PF-06865571 in Period 1 at times 
specified in the Schedule of Activities.  Feces will be collected following IV administration 
of [14C]PF-06865571 in Period 2 at times specified in the Schedule of Activities, and may be 
analyzed for total 14C and/or [14C]PF-06865571 determination and/or metabolic profiling/ID
if the fraction of dose excreted as parent in feces of Period 1 is 0.25 greater than unabsorbed 
drug (1-Fa), indicating biliary and/or GI excretion may be a major pathway for parent drug 
clearance (e.g. greater than 25% of total clearance).
Fecal voids will be collected at the clinic and immediately frozen.  The sample will be 
labeled and frozen at approximately -20C. 
Total fecal mass is to be recorded for each 24-hour period. Each bowel movement must be 
collected.  Time and date must be recorded.  
In the event of diarrhea during the study, all diarrhea, including any swabbing and 
contaminated linen, should be collected, labeled, and stored in appropriate containers 
at -20C for possible analysis of radioactivity.  Following completion of radioanalysis and 
subsample collections for metabolite profiling/ID, the remaining bulk fecal homogenate will 
be discarded upon approval from the sponsor.
Details regarding the collection, processing, storage and shipping of the feces samples will be 
provided in the lab manual.
All feces samples must be processed and shipped as indicated to maintain sample integrity.  
Any deviations from the processing steps, including any actions taken, must be documented 
and reported to the sponsor.  On a case-by-case basis, the sponsor may make a determination 
as to whether sample integrity has been compromised.  Any sample deemed outside of 
established stability, or of questionable integrity, will be considered a protocol deviation.
8.5.6. Emesis
If emesis occurs within 24 hours after oral administration of [14C]PF-06865571 (Period 1
only), then the vomitus must be collected and stored for a radioactivity assessment.  All 
emesis including any swabbing, contaminated linens and facial tissues used to collect bodily 
discharge; eg, nose bleeding clean-up tissue and any emesis related clean-up is to be 
collected and stored at -20C for possible analysis of radioactivity. 
Details regarding the collection, processing, storage and shipping of the samples will be 
provided in the lab manual.  
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.


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8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study. Any genetic analysis, if 
conducted, will not be part of this study report.
8.7.2. Banked Biospecimens for Genetics
A 2 mL blood sample optimized for DNA isolation Prep D1.5 will be collected as local 
regulations and IRBs/ECs allow.
Banked Biospecimens may be used for research related to the study intervention(s) and/or
NAFLD/NASH.  Genes and other analytes (eg, proteins, RNA, nondrug metabolites) may be 
studied using the banked samples. 
See Appendix 5 for information regarding genetic research.  Details on processes for 
collection and shipment of these samples can be found in supporting documentation.
8.8. Biomarkers
Collection of samples for biomarker research is also part of this study. 
The following sample for biomarker research are required and will be collected from all 
participants in this study as specified in the Schedule of Activities:

Whole blood (Prep B1) Banked Biospecimen optimized for plasma
8.8.1. Specified Gene Expression (RNA) Research
Specified gene expression (RNA) research is not included in this study.
8.8.2. Specified Protein Research
Specified protein research is not included in this study.
8.8.3. Specified Metabolomic Research
Specified metabolomic research is not included in this study.
8.8.4. Banked Biospecimens for Biomarkers
Additional Banked Biospecimens in this study are:

10 mL whole blood Prep B1 optimized for plasma
Banked Biospecimens will be collected as local regulations and IRB/ECs allow.  
Banked Biospecimens may be used for research related to the study intervention(s) and 
NAFLD/NASH.  Genes and other analytes (eg, proteins, RNA, nondrug metabolites) may be 
studied using the banked samples. 


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See Appendix 5 for information regarding genetic research.  Details on processes for 
collection and shipment of these samples can be found in supporting documentation. 
8.9. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
No statistical hypothesis is tested in this study.
9.2. Sample Size Determination
A sample size of 6 male participants has been chosen based on the industry standard sample 
size for ADME Mass Balance studies and radiolabeled tracer studies.  This sample size was 
not chosen based on any empirical data or hypothesis testing criteria.
Participants who withdraw from the study, for non-safety reasons, may be replaced if the 
number of participants with evaluable data is less than 4.
9.3. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant
Analysis Set
Description
Evaluable
All participants assigned to study intervention and who take at 
least 1 dose of study intervention.
CCI


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Participant
Analysis Set
Description
Extent of Excretion
Extent of excretion population is defined as all participants who 
have received 1 dose of [14C]PF-06865571 and who have 
evaluable total radioactivity concentration (urinary and fecal) data 
and who had no protocol deviations or AEs (such as vomiting of 
the dose, diarrhoea or severe constipation) that may have affected 
the extent of excretion analysis.
PK Concentration
The PK concentration population for PF-06895571 is defined as 
all participants who receive at least 1 dose of PF-06895571 and 
who have at least 1 measurable concentration of PF-06895571. 
The PK concentration population for 14C is defined as all
participants dosed with [14C]PF-06895571, who have at least
one 14C measurement.
PK Parameter
The PK parameter analysis population for PF-06895571 is 
defined as all participants treated who have at least 1 of the PF-
06895571 PK parameters of interest.  The PK parameter analysis 
population for 14C analysis is defined as all participants treated 
who have at least one of the 14C parameters of interest.  The PK 
concentration and PK parameter analysis sets may differ.
Safety
All participants assigned to study intervention and who take at 
least 1 dose of study intervention.  Participants will be analyzed 
according to the product they actually received.
9.4. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. Primary Endpoint(s)
9.4.1.1. Extent of Excretion (Period 1)
Radioactivity excreted in urine and/or feces will be reported as the percentage of the 
administered radioactivity excreted at each time interval, cumulatively through that interval 
and the total percent of dose recovered in urine and/or feces. 
Percent recovery and cumulative recovery of total radioactivity in urine, feces and emesis
(if any) will be determined based on total administered dose.


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Note: While the total percentage of dose excreted is the primary endpoint, the percentage of 
the administered radioactivity excreted at each time interval and cumulatively through that 
interval are tertiary endpoints. 
Individual participant and median data profiles will be graphically presented for the 
cumulative recovery of radioactivity in urine, feces and their combination.  The total 
recovery of radioactivity in urine, feces and their combination will be listed and summarized 
using descriptive statistics.  Where possible, the rate of excretion of radioactivity will be 
estimated.
9.4.1.2. Metabolic Profiling/Identification (Period 1)
Plasma, urine and fecal samples will be analyzed for metabolites of PF-06865571.  Major 
metabolites of PF-06865571 in plasma, urine, and feces following oral dose of [14C]PF-
06865571 will be identified if possible.  Results of the metabolic profiling analysis will be 
detailed in a separate report and will be summarized within the CSR.
9.4.2. Secondary Endpoint(s)
9.4.2.1. Pharmacokinetic Parameters
9.4.2.1.1. Plasma
The PF-06865571 PK parameters following a single dose administration of unlabeled 
PF-06865571 (oral) and microtracer dose of [14C]PF-06865571 (oral and IV) will be derived, 
where appropriate, from the concentration-time profiles as outlined below:

Parameters for total 14C (14C oral microtracer) will be derived for Period 1 only;

Parameters for PF-06865571 after oral doses of 14C oral microtracer and unlabeled 
PF-06865571 for Periods 1 and 2, respectively and for [14C]PF-06865571 after 14C IV 
microtracer for Period 2 will be derived. 
Parameter
Definition
Method of Determination
AUClast
Area under the plasma 
concentration-time profile from 
time zero to time of the last 
quantifiable concentration (Clast)
Linear/Log trapezoidal rule
AUClast(dn)
Dose normalized AUClast
AUClast/Dose
AUCinfa
Area under the plasma 
concentration-time profile from 
time zero extrapolated to infinite 
time
AUClast + (Clast*/kel), where Clast* is the 
predicted plasma concentration at the 
last quantifiable time point estimated 
from the log-linear regression analysis
AUCinf(dn)a
Dose normalized area under the 
plasma concentration-time profile 
from time zero extrapolated to 
infinite time
AUCinf/Dose


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Parameter
Definition
Method of Determination
Cmax
Maximum plasma concentration
Observed directly from data
Cmax(dn)
Dose normalized maximum plasma 
concentration.
Cmax/Dose
Tmax
Time for Cmax
Observed directly from data as time of 
first occurrence
t½a
Terminal elimination half-life
Loge(2)/kel, where kel is the terminal 
phase rate constant calculated by a linear 
regression of the loglinear concentration
time curve.  Only those data points 
judged to describe the terminal loglinear
decline will be used in the regression
CL/Fa (oral) Apparent clearance following oral 
administration
Dose/AUCinf
CLa (IV)
Systemic clearance
Dose/AUCinf
Vz/Fa (oral) 
Apparent volume of distribution 
following oral administration
Dose/(AUCinf*kel)
Vssa (IV)
Steady-state volume of distribution 
following IV infusion
Vss=CL × [MRT-(infusion time/2)]
where MRT is the Mean Residence Time and is
calculated as AUMCinf/AUCinf
a.
If data permit.
Actual PK sampling times will be used in the derivation of PK parameters, defined relative to 
the oral dose for the oral parameters and relative to the start of the 15-minute IV infusion for 
the IV parameters.  Actual administered 14C doses will be used for the total 14C and 
[14C]PF-06865571 PK parameter calculations.
Plasma PK parameters above will be listed and summarized descriptively by analyte (total 
14C, unlabeled PF-06865571, and [14C]PF-06865571) and treatment, as applicable.  The
descriptive summary, concentration and PK parameters will be presented in appropriate
tables and figures.  
9.4.2.1.2. Absolute Oral Bioavailability (F)
F will be estimated as the ratio of adjusted geometric means of dose-normalized AUCinf (if 
data permit, otherwise AUClast) for oral unlabeled PF-06865571 and IV labeled 
14C-PF-06865571 in plasma (from Period 2 only) which is equivalent to the following 
equation:
F = [PF-06865571_AUCpo/[14C]PF-06865571_AUCiv]×[ [14C]PF-06865571_Doseiv/ 
PF-06865571_Dosepo]


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
Geometric Mean Ratio and 90% confidence interval: Natural log transformed AUCinf(dn) 
(if data permit) and AUClast(dn) from Period 2 will be analyzed using a mixed effect 
model with treatment as a fixed effect and participant as a random effect.  Estimates of 
the adjusted (least squares) mean differences (Test-Reference) and the corresponding 
90% CI will be obtained from the model.  The adjusted mean differences and 90% CIs 
for the differences will be exponentiated to provide estimates of the ratio of adjusted 
geometric means (Test/Reference) and 90% CI for the ratio.  IV [14C]PF-06865571 is the 
Reference formulation and unlabeled oral PF-06865571 is the Test formulation. 
9.4.2.1.3. Fraction Absorbed (Fa)
9.4.2.1.3.1. Urine Parameters
Following urine parameters will be calculated following single dose administration of a 
microtracer dose of [14C]PF-06865571 (oral and IV administration).  Residual 14C levels 
from Period 1 will be accounted for using an appropriate method, based on AMS principles 
and methodology.
Parameter
Definition
Method of Determination
Total 14C_Urine_PO
Total radioactivity excreted into the urine 
postdose following oral administration of 
[14C]PF-06865571 microtracer dose
Sum of [14C urine concentration × sample 
volume] for each collection interval
Total 14C_Urine_IV
Total radioactivity excreted into the urine 
following IV administration of 
[14C]PF-06865571 microtracer dose
Sum of [14C urine concentration × sample 
volume] for each collection interval
%14C_Urine_PO
Percent of the radioactive dose administered 
that is excreted in the urine following oral 
administration
Total 14C_Urine_PO/14C Dosepo × 100
Where 14C Dosepo is the dose of 14C 
following oral administration of 
[14C]PF-06865571
%14C_Urine_IV
Percent of the radioactive dose administered 
that is excreted in the urine following IV 
administration
Total 14C _Urine_IV/14C Doseiv × 100
Where 14C Doseiv is the dose of 14C 
following IV administration of 
[14C]PF-06865571
Total urine 14C amounts, percent 14C dose will be listed by treatment (oral in Period 1 and IV 
in Period 2) and summarized using descriptive statistics.  
9.4.2.1.3.2. Calculation of Fa
Fa will be estimated as the ratio of the adjusted geometric means of % of administered 
radioactive dose excreted into the urine following oral and IV administration of 
[14C]PF-06865571 microtracer dose over the same collection time (up to 48 hours post dose) 
in Periods 1 and 2, respectively: 
Fa = [% 14C_Urine_PO/% 14C_Urine_IV];


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•
Geometric Mean Ratio and 90% confidence interval: Natural log transformed % Total 
14C in Urine from Period 1 and Period 2 will be analyzed using a mixed effect model with 
treatment as a fixed effect and participant as a random effect.  Estimates of the adjusted 
(least squares) mean differences (Test-Reference) and the corresponding 90% CI will be 
obtained from the model.  The adjusted mean differences and 90% CIs for the differences 
will be exponentiated to provide estimates of the ratio of adjusted geometric means 
(Test/Reference) and 90% CI for the ratio.  Total 14C_Urine_IV is the Reference 
formulation and Total 14C_Urine_PO is the Test formulation. 
Theoretically Fa would be expected to be greater than F. In the event that F is estimated to be 
greater than Fa, the greater of the 2 values will be used to represent the fraction of 
PF-06865571 absorbed. PF-06865571 will be considered highly permeable if either F or Fa 
is greater than 0.85 (as per BCS guidance).9
9.4.3. Tertiary/Exploratory Endpoint(s)
 
 
 
 
9.4.3.2. Cumulative Rate of Excretion (Period 1)
See Section 9.4.1.1.
9.4.3.3. Pharmacokinetics Parameters (Unlabeled PF-06865571 - Period 2)
See Section 9.4.2.1.1.
9.4.4. Other 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 
CCI


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data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted.  Demographic data collected at screening will be reported.
9.4.5. Other Analyse(s)
Pharmacogenomic or biomarker data from Banked Biospecimens may be collected during or 
after the trial and retained for future analyses; the results of such analyses are not planned to 
be included in the CSR.
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 and/or supporting clinical development. 
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will not use a DMC. 


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


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


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Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research.  The optional 
additional research does not require the collection of any further samples. The investigator 
or authorized designee will explain to each participant the objectives of the additional
research. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period. A separate 
signature will be required to document a participant's agreement to allow specimens to be 
used for additional research. Participants who decline to participate in this optional
additional research will not provide this separate signature.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site will be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations.  In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.


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www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted.  These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website.  Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.


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10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the Study 
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.


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The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in Study Monitoring Plan.
Description of the use of computerized system is documented in the Data Management Plan.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;


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
Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
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.


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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 portal. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 
problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  For sites other than a Pfizer CRU, the contact number is not intended 
for use by the participant directly, and if a participant calls that number, he or she will be 
directed back to the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the Schedule of 
Activities of this protocol.  Additional laboratory results may be reported on these samples as 
a result of the method of analysis or the type of analyzer used by the clinical laboratory, or as 
derived from calculated values.  These additional tests would not require additional 
collection of blood.  Unscheduled clinical laboratory measurements may be obtained at any 
time during the study to assess any perceived safety issues. Participants may undergo random 
urine drug and cotinine testing at the discretion of the investigator
Table 1.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils 
(Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN
Serum creatinine
Serum glucose 
(fasting)
Calcium
Sodium
Potassium
Chloride
Total 
CO2 (bicarbonate)
AST, ALT
Total bilirubin
Direct (conjugated) 
bilirubina
Indirect 
(unconjugated) 
bilirubina
Alkaline phosphatase
Uric acid
Albumin
Total protein
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte 
esterase
Urobilinogen
Urine bilirubin
Microscopyb
At screening only unless 
otherwise stated:

Urine drug screening, 
Period 1, Day -1c

Urine cotinine screening, 
Period 1, Day -1

HBsAg

HCVAb

HIV

COVID-19 testingd
a.
To be assessed as reflex tests when total bilirubin is > ULN.
b.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
c.
The minimum requirement for drug screening includes cocaine, THC, opiates/opioids, 
benzodiazepines, and amphetamines (others are site and study specific).
d.
Testing for COVID-19 pathogen (SARS-CoV-2) by PCR will be performed at each visit to the CRU 
(Screening and Admission). For participants admitted for residence in the CRU, a subsequent 
COVID-19 test will be performed 2x/week at a minimum.
Investigators must document their review of each laboratory safety report.
Any remaining serum/plasma from samples collected for clinical safety laboratory 
measurements at baseline and at all times after dose administration may be retained and 
stored for the duration of the study.  Upon completion of the study, these retained safety 
samples may be used for the assessment of exploratory safety biomarkers or unexpected 


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safety findings.  These data will not be included in the CSR.  Samples to be used for this 
purpose will be shipped to either a Pfizer-approved BBS facility or other designated 
laboratory and retained for up to 1 year following the completion of the study.


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or 
not considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (eg, ECG, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator. Any 
abnormal laboratory test results that meet any of the conditions below must be 
recorded as an AE:

Is associated with accompanying symptoms;

Requires additional diagnostic testing or medical/surgical intervention;

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition including either 
an increase in frequency and/or intensity of the condition.

New 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.


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Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF 
and for reporting serious adverse events on the CT SAE Report Form to Pfizer Safety.  
These requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; 
and (3) exposure to the study intervention under study during pregnancy or 
breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must 
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 study 
intervention under study 
during pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (and EDP 
supplemental form for 
EDP)  
Note:  Include all SAEs
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.


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


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


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


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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
No contraception methods are required for male participants in this study as the calculated 
safety margin is ≥100-fold between the estimated maternal exposure due to seminal transfer 
and the NOAEL for serious manifestations of developmental toxicity in nonclinical studies.


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10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis.

The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.

The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to study intervention or study interventions of this class to 
understand treatments for the disease(s) under study or the disease(s) themselves.

The results of genetic analyses may be reported in the CSR or in a separate study 
summary, or may be used for internal decision making without being included in a 
study report.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained as indicated:

Samples for banking will be stored indefinitely or for another period as per local 
requirements.  

Participants may withdraw their consent for the storage and/or use of their Banked 
Biospecimens at any time by making a request to the investigator; in this case, any 
remaining material will be destroyed.  Data already generated from the samples will 
be retained to protect the integrity of existing analyses.  

Banked Biospecimens will be labeled with a code.  The key between the code and the 
participant’s personally identifying information (eg, name, address) will be held at the 
study site and will not be provided to the sample bank.


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


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


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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as AEs

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by 60 msec from 
baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate: ie, 
rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30 seconds’
duration.

Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive 
ventricular complexes.
ECG Findings That May Qualify as SAEs

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia.

Asystole:

In awake, symptom-free participants in sinus rhythm, with documented 
periods of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an 
escape rhythm that is below the AV node. 

In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).


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


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10.8. Appendix 8: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
ACCi
acetyl-CoA carboxylase inhibitor
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
Aetau
cumulative amount of drug recovered unchanged in the urine 
during a dosing interval
ALT
alanine aminotransferase
AMS
accelerator mass spectrometry
API
active pharmaceutical ingredient
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
AUCinf(dn)
dose normalized AUCinf
AUClast
area under the concentration-time curve from 0 to time of last 
measurable concentration
AUClast(dn)
dose normalized AUClast
AUCtau
area under the concentration-time curve at steady state over the 
dosing interval 
AUMCinf
area under the first moment curve from time 0 to infinity
AV
atrioventricular
BA
bioavailability
BBS
Biospecimen Banking System
BCRP
breast cancer resistance protein
BCS
Biopharmaceutics Classification System
BE
bioequivalence
BID
twice a day
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BUN
blood urea nitrogen
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CL/F
apparent clearance following oral administration
CLr
renal clearance
Clast
last quantifiable concentration 
Cmax
maximum observed concentration


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Abbreviation
Term
Cmax(dn)
dose normalized Cmax
COVID-19
coronavirus disease 2019
CO2
carbon dioxide (bicarbonate)
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
Clinical Study Report
CT
clinical trial
CYP
cytochrome P450
DAG
diacylglycerol
DDI
drug-drug interaction
DGAT
diacylglycerol acyltransferase
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DNL
de novo lipogenesis
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDP
exposure during pregnancy
EDR
extemporaneous dispensing record
EMA
European Medicines Agency
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
F
absolute oral bioavailability
Fa
fraction absorbed
Fg
fraction escaping gut metabolism
Fh
fraction escaping hepatic first-pass elimination
F/U
follow up
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HBsAg 
hepatitis B surface antigen
HCVAb
hepatitis C antibody
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HR
heart rate
IB
Investigator’s Brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICRP
International Commission on Radiological Protection
ID
identification


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Abbreviation
Term
Ig
immunoglobulin
IND
Investigational New Drug 
INR
international normalized ratio
IPAL
Investigational Product Accountability Log
IRB
Institutional Review Board
IV
intravenous
K2EDTA
dipotassium ethylene diamine tetraacetic acid 
LBBB
left bundle branch block
LC/MS
liquid chromatography tandem mass spectrometry
LFT
liver function test
Loge
natural logarithm
MATE
multidrug and toxic compound extrusion transporter
mBCRP
mouse breast cancer resistance protein
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDR
multi-drug resistance protein
mrem
millirem
MRT 
mean residence time
msec
millisecond
N/A
not applicable
Nab
neutralizing antibodies
NAFLD
nonalcoholic fatty liver disease 
NASH
nonalcoholic steatohepatitis 
nCi
nanocurie
NOAEL
no-observed-adverse-effect level
OCT
organic cation transporter
PCR
polymerase chain reaction
PD
pharmacodynamic(s)
PE
physical examination
P-gp
P-glycoprotein
PI
principal investigator
PK
pharmacokinetic(s)
PO
orally
PT
prothrombin time
PVC
premature ventricular contraction/complex
P1
Period 1
P2
Period 2
QA
quality assurance
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
Q8H
every 8 hours


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Abbreviation
Term
qual
qualitative
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SCr
serum creatinine
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SSID
single subject identifier
SUSAR
suspected unexpected serious adverse reaction
t½
terminal elimination half-life 
TA
technical agreement 
TEAE
treatment-emergent adverse event
TBili
total bilirubin
TG
triglyceride
THC
tetrahydrocannabinol
Tmax
time to reach maximum observed concentration
UGT
uridine diphosphate-glucuronyltransferase 
ULN
upper limit of normal
US
United States
Vss
steady-state volume of distribution following IV infusion
Vz/F
apparent volume of distribution following oral administration
VLDL
very low density lipoprotein
WBC
white blood cell


PF-06865571
Protocol C2541007
Final Protocol, 11 Dec 2020
PFIZER CONFIDENTIAL
Page 84
11. REFERENCES
1.
Yen CL, Stone SJ, Koliwad S, et al.  Thematic review series: glycerolipids. DGAT
enzymes and triacylglycerol biosynthesis.  J Lipid Res. 2008;49(11):2283-301.
2.
Buhman KK, Smith SJ, Stone SJ, et al.  DGAT1 is not essential for intestinal 
triacylglycerol absorption or chylomicron synthesis.  J Biol Chem.
2002;277(28):25474-9.
3.
Cases S, Stone SJ, Zhou P, et al.  Cloning of DGAT2, a second mammalian 
diacylglycerol acyltransferase, and related family members.  J Biol Chem.
2001;276(42):38870-6.
4.
Choi CS, Savage DB. Suppression of diacylglycerol acyltransferase-2 (DGAT2), but 
not DGAT1, with antisense oligonucleotides reverses diet-induced hepatic steatosis and 
insulin resistance. J Biol Chem. 2007;282(31):22678-88.
5.
Yu XX, Murray SF, Pandey SK, et al.  Antisense oligonucleotide reduction of DGAT2 
expression improves hepatic steatosis and hyperlipidemia in obese mice.  Hepatology.
2005;42(2):362-71.
6.
Liu Y, Millar JS, Cromley DA, et al.  Knockdown of acyl-CoA:diacylglycerol 
acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion 
in mice.  Biochim Biophys Acta. 2008;1781(3):97-104.
7.
International Commission on Radiological Protection. 1990 Recommendations of the 
International Commission on Radiological Protection. Ann. ICRP 1991. 21, 1–201.
8.
Abdelmalek MF, Lazo M, Horska A, et al. Fatty Liver Subgroup of Look, A. R. G., 
Higher dietary fructose is associated with impaired hepatic adenosine triphosphate 
homeostasis in obese individuals with type 2 diabetes. Hepatology. 2012;56:952-60.
9.
FDA Guidance “Waiver of In Vivo Bioavailability and Bioequivalence Studies for 
Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics
Classification System”. December 2017.
10. Banholzer ML, Wandel C, Barrow P, et al. Clinical trial considerations on male 
contraception and collection of pregnancy information from female partner: update. 
Clin Transl Med. 2016;5(1)(Dec):23.
11. ICH Topic M3 (R2). Non-clinical safety studies for the conduct of human clinical trials
and marketing authorization for pharmaceuticals. International Conference on
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
Human Use (2009).

SAP_001.pdf: 
Protocol C2541007 (PF-06865571) Statistical Analysis Plan
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PFIZER CONFIDENTIAL
Protocol C2541007
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY IN 
HEALTHY ADULT MALE PARTICIPANTS TO ASSESS THE EXTENT 
OF EXCRETION, ABSOLUTE BIOAVAILABILITY, FRACTION 
ABSORBED, AND PHARMACOKINETICS OF [14C]PF-06865571 USING 
A 14C-MICROTRACER APPROACH
Statistical Analysis Plan 
(SAP)
Version:
1.0
SAP Author: 
(FSP Statistician 
 
)
Date:
01-Mar-2021
PPD
PPD


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PFIZER CONFIDENTIAL
Revision History
Version
Date
Author(s)
Summary of Changes/Comments
1.0
March 01, 2021
Not Applicable
NOTE: Italicized text within this document has been taken verbatim from the Protocol.
PPD


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PFIZER CONFIDENTIAL
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................5
LIST OF FIGURES ...................................................................................................................5
APPENDICES ...........................................................................................................................5
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................6
2. INTRODUCTION .................................................................................................................6
2.1. Study Design .............................................................................................................6
2.2. Study Objectives .......................................................................................................7
2.2.1. Primary Objectives .......................................................................................7
2.2.2. Secondary Objectives ...................................................................................7
2.2.3. Tertiary/Exploratory Objectives ...................................................................8
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................8
4. HYPOTHESES AND DECISION RULES...........................................................................8
4.1. Statistical Hypotheses ...............................................................................................8
4.2. Statistical Decision Rules..........................................................................................8
5. ANALYSIS SETS .................................................................................................................8
5.1. Evaluable Analysis Set..............................................................................................8
5.2. Extent of Excretion Analysis Set ..............................................................................8
5.3. Pharmacokinetic (PK) Analysis Set ..........................................................................9
5.3.1. Concentration Analysis Set...........................................................................9
5.3.2. Parameter Analysis Set.................................................................................9
5.4. Pharmacodynamic Analysis Set................................................................................9
5.5. Safety Analysis Set....................................................................................................9
5.6. Other Analysis Sets ...................................................................................................9
5.7. Treatment Misallocations..........................................................................................9
5.8. Protocol Deviations...................................................................................................9
5.8.1. Deviations Assessed Prior to Randomization...............................................9
5.8.2. Deviations Assessed Post-Randomization..................................................10
6. ENDPOINTS AND COVARIATES ...................................................................................10
6.1. Efficacy Endpoint(s) ...............................................................................................10
6.2. Primary Endpoints...................................................................................................10


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6.3. Secondary Endpoints...............................................................................................10
6.4. Tertiary/Exploratory Endpoints...............................................................................10
6.5. Safety Endpoints .....................................................................................................11
6.6. Other Endpoints.......................................................................................................11
6.6.1. PK Endpoints..............................................................................................11
6.6.1.1. Plasma PK Analysis ..................................................................11
6.6.2. PD Endpoints..............................................................................................12
6.7. Covariates................................................................................................................12
7. HANDLING OF MISSING VALUES ................................................................................12
7.1. Concentrations Below the Limit of Quantification.................................................12
7.2. Deviations, Missing Concentrations and Anomalous Values .................................12
7.3. Pharmacokinetic Parameters ...................................................................................12
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................13
8.1. Statistical Methods ..................................................................................................13
8.2. Statistical Analyses .................................................................................................13
8.2.1. Extent of Excretion (Period 1)....................................................................13
8.2.2. Metabolic Profiling/Identification (Period 1).............................................14
8.2.3. Pharmacokinetic Analysis ..........................................................................14
8.2.3.1. Plasma .......................................................................................14
8.2.3.2. Absolute Oral Bioavailability (F)..............................................14
8.2.3.3. Fraction Absorbed (Fa) .............................................................15
8.3. Safety Analysis........................................................................................................17
8.3.1. Treatment and Disposition of Participants .................................................18
8.3.2. Demographic and Clinical Examination Data............................................18
8.3.3. Discontinuation(s).......................................................................................18
8.3.4. Adverse Events...........................................................................................18
8.3.5. Laboratory Data..........................................................................................18
8.3.6. Vital Signs Data..........................................................................................18
8.3.7. ECG Data....................................................................................................18
8.3.8. Other Safety Data .......................................................................................18
8.3.9. Concomitant Treatments.............................................................................18


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8.3.10. Screening and Other Special Purpose Data ..............................................19
8.3.12. Banked Bio-specimen data .......................................................................19
9. REFERENCES ....................................................................................................................19
10. APPENDICES ...................................................................................................................20
LIST OF TABLES
Table 1.
Noncompartmental PK Parameters of Plasma..........................................11
Table 2.
PK Parameters to be Summarized Descriptively......................................16
LIST OF FIGURES
Figure 1.
Two Period Fixed Sequence Study Design ................................................6
APPENDICES
Appendix 1. SAS CODE FOR ANALYSES...........................................................................20
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1. AMENDMENTS FROM PREVIOUS VERSION(S) 
None.
2. INTRODUCTION
PF-06865571 is a diacylglycerol acyltransferase 2 (DGAT2) inhibitor that is currently being
developed for the treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis.  
The purpose of this study is to assess the extent of excretion of PF-06865571 as well as the
absolute bioavailability, fraction absorbed and pharmacokinetics of PF-06865571 in healthy
male participants using a 14C microtracer dose approach.
2.1. Study Design
This study is a Phase 1, open-label, non-randomized, 2-period, fixed-sequence, single-dose
study of PF-06865571 in healthy male participants to characterize the ADME properties of
[14C]PF-06865571 following oral administration; and to evaluate the absolute oral
bioavailability (F) and fraction absorbed (Fa) of PF-06865571 following oral administration
of unlabeled PF-06865571 and IV administration of [14C]PF-06865571.
In this study, 6 participants will be enrolled to ensure evaluable data is acquired in at least 
4 participants. Each participant will receive 2 regimens (A and B) in Periods 1 and 2,
respectively, as outlined in Figure 1. Participants who withdraw from the study may be
replaced if the number of evaluable participants is less than 4.
Figure 1.
Two Period Fixed Sequence Study Design
* Completion of Period 1 (1 participant at a time) when at least 1 of 3 criteria are met: (1) ≥90% of radioactive
dose has been recovered in urine+feces+emesis (if any); (2) <1% of radioactive dose has been recovered in
urine+feces during 24H interval over 2 consecutive days; (3) participant has reached Day 21 (in Period 1).  At 
the latest, Period 2, Day -1 would occur on the same day as Period 1, Day 21.


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PFIZER CONFIDENTIAL
Regimen A in Period 1: An oral dose of 300 mg PF-06865571 containing approximately
300 nCi 14C (ie, radiolabeled PF-06865571).
Regimen B in Period 2: An oral dose of 300 mg unlabeled PF-06865571 followed at Tmax by
an IV dose of 300 nCi [14C] in 100 µg of PF-06865571 (3 µCi/mg active drug). 
Screening will occur within 42 days of the first dose of the investigational product in
Period 1. All participants will provide informed consent and undergo screening evaluations
to determine their eligibility.
Eligible participants will be admitted to the CRU on Day -1 of Period 1 and scheduled to
remain in the CRU through the completion of Period 2. As such, inpatient stay will be for a
total duration of 12 days (minimum) to 25 days (maximum). Each participant will have
1 follow-up phone call that will occur at least 28 days and up to 35 days following the last
dose of investigational product to assess for AEs and SAEs.
A participant is considered to have completed the study if he has completed all phases of the
study, including the last scheduled procedure as mentioned in the Schedule of Activities in 
the study protocol.
2.2. Study Objectives
2.2.1. Primary Objectives

To characterize the extent of excretion of total radioactivity in urine and feces 
following administration of a single oral dose of [14C] PF-06865571.

To characterize the metabolic profile and identify circulating and excreted 
metabolites following administration of a single oral dose of [14C] PF-06865571.
2.2.2. Secondary Objectives

To quantify plasma PK parameters of PF-06865571 and total radioactivity following 
administration of a single oral dose of [14C] PF-06865571.

To quantify plasma PK parameters of PF-06865571 following administration of a 
single, IV, microtracer of [14C] PF-06865571.

To determine the absolute oral bioavailability (F) of PF-06865571 following 
administration of a single oral dose of PF-06865571 compared to a single IV 
microtracer of [14C] PF-06865571.

To determine the fraction of the dose absorbed (Fa) following administration of a 
single oral dose of [14C] PF-06865571.


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2.2.3. Tertiary/Exploratory Objectives
•
To characterize cumulative rate of excretion of total radioactivity in urine and feces 
over time following administration of a single oral dose of [14C] PF‑06865571.
•
To quantify plasma PK parameters of PF-06865571 in plasma following 
administration of a single oral dose of unlabeled PF-06865571.
 
•
To evaluate the safety and tolerability of PF-06865571, administered as a single oral 
dose of [14C] PF-06865571 or a single oral dose of PF-06865571 followed by 
administration of a single IV microtracer of [14C] PF-06865571.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
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 and/or supporting clinical development. 
Final analysis will follow the official database release.  As this will be an open-label study, 
there is no formal unblinding of the randomization code.
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
No statistical hypothesis is tested in this study.
4.2. Statistical Decision Rules
No decision rules are required.
5. ANALYSIS SETS
5.1. Evaluable Analysis Set
All participants assigned to study intervention and who take at least 1 dose of study 
intervention.
5.2. Extent of Excretion Analysis Set
Extent of excretion population is defined as all participants who have received 1 dose of 
[14C] PF-06865571 and who have evaluable total radioactivity concentration (urinary and 
fecal) data and who had no protocol deviations or AEs (such as vomiting of the dose, 
diarrhoea or severe constipation) that may have affected the extent of excretion analysis.
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5.3. Pharmacokinetic (PK) Analysis Set
5.3.1. Concentration Analysis Set

The PK concentration population for unlabelled PF-06895571 is defined as all 
participants who receive at least 1 dose of unlabelled PF-06895571 and who have at 
least 1 measurable concentration of unlabelled PF-06895571.

The PK concentration population for 14C is defined as all participants dosed with 
[14C] PF-06895571, who have at least one 14C measurement.
5.3.2. Parameter Analysis Set
The PK parameter analysis population for PF-06895571 is defined as all participants treated 
who have at least 1 of the PF-06895571 PK parameters of interest. The PK parameter 
analysis population for 14C analysis is defined as all participants treated who have at least 
one of the 14C parameters of interest. The PK concentration and PK parameter analysis sets 
may differ.
5.4. Pharmacodynamic Analysis Set
None.
5.5. Safety Analysis Set
All participants assigned to study intervention and who take at least 1 dose of study 
intervention. Participants will be analyzed according to the product they actually received.
5.6. Other Analysis Sets
None.
5.7. Treatment Misallocations 
This is a nonrandomized study.  All participants will receive the same treatment.
5.8. 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.
5.8.1. 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.


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PFIZER CONFIDENTIAL
5.8.2. 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.
6. ENDPOINTS AND COVARIATES
6.1. Efficacy Endpoint(s)
None.
6.2. Primary Endpoints

Total recovery of radioactivity in urine, feces and total excreta (urine + feces) as 
percentage of total radioactive dose administered.

Metabolic profiling/identification and determination of relative abundance of 
[14C] PF-06865571 and the metabolites of [14C] PF-06865571 in plasma, urine and 
feces.
6.3. Secondary Endpoints

Period 1: AUClast, Cmax, Tmax, and if data permit, AUCinf and t½ to describe single oral 
dose of:

Total radioactivity in plasma;

PF-06865571 in plasma.

[14C]PF-06865571 (Period 2): AUClast, Cmax, Tmax, and if data permit, t½, AUCinf, CL 
and Vss.

Plasma AUCinf of oral unlabeled PF-06865571 and IV microtracer of 
[14C] PF-06865571 in Period 2 only.

Total urinary radioactivity following oral administration of [14C] PF-06865571 in 
Period 1 and IV microtracer administration of [14C] PF-06865571 in Period 2.
6.4. Tertiary/Exploratory Endpoints

Cumulative recovery of radioactivity in urine and feces, and total excreta 
(urine + feces) over time as a percentage of total radioactive dose administered.

PF-06865571 plasma (Period 2): AUClast, Cmax, Tmax, and if data permit, t½, AUCinf, 
CL/F, Vz/F.


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6.5. Safety Endpoints
An adverse event is considered a treatment emergent if the event started during the effective 
duration of treatment.
Events that occur in a non-treatment period (for example, Washout or Follow-up) will be 
counted as treatment emergent and attributed to the previous treatment taken.
The following data are considered in standard safety summaries (see protocol for collection 
days and list of parameters):
•
adverse events;
•
laboratory data.
6.6. Other Endpoints
6.6.1. PK Endpoints
6.6.1.1. Plasma PK Analysis
Blood samples will be collected according to the Schedule of Activities given in the protocol. 
Blood will be analyzed for concentrations of total radioactivity.  Plasma will be analyzed for 
concentrations of PF-06865571 and (if possible) its major metabolite(s).
The following parameters will be determined using standard non-compartmental methods
and will be listed and summarized descriptively:
Table 1.
Noncompartmental PK Parameters of Plasma
After oral dose of
[14C] PF-06865571
(Period 1)
After oral dose of
PF-06865571
(Period 2)
After IV dose of
[14C] PF-06865571
(Period 2)
Parameter
Analysis Scale
PF-06865571
Total 14C
PF-06865571
[14C] PF-06865571
AUClast
ln
D
D
D
D
AUClast(dn)
ln
D
D
D
D
AUCinf*
ln
D
D
D
D
AUCinf(dn)
ln
D
D
D
D
Cmax
ln
D
D
D
D
Cmax(dn)
ln
D
D
D
D
Tmax
R
D
D
D
D
t1/2*
R
D
D
D
D
CL/F* (oral)
ln
D
D
D
NA
CL* (IV)
ln
NA
NA
NA
D
Vz/F* (oral)
ln
D
D
D
NA
Vss* (IV)
ln
NA
NA
NA
D
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Key: A=analyzed using statistical model, D=displayed with descriptive statistics,
ln=natural-log transformed, R=raw (untransformed), *=if data permits, 
dn=dose normalized to a 1 mg dose, IV=intravenous, NA=not applicable.
Additionally, Tlast will be provided as a supportive parameter for AUClast.  Tlast will be listed 
only and not summarized. 
6.6.2. PD Endpoints
None.
6.7. Covariates
None.
7. HANDLING OF MISSING VALUES
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.
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. In the event that 
actual time is missing, nominal time may be used. 
If a PK parameter cannot be derived from a participant’s concentration data, the parameter 
will be coded as NC (ie, not calculated). (Note that NC values will not be generated beyond 
the day that a participant discontinues). 


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PFIZER CONFIDENTIAL
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular treatment group/analyte with ≥3 evaluable measurements.
For statistical analyses (ie, mixed effect model), 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, or not completing the meal before dosing), 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
Precision of the estimate of PK parameters will be determined by constructing 
90% confidence intervals around the estimated difference between the Test and Reference 
treatments using a mixed effects model based on natural log transformed data.  The mixed 
effects model will be implemented using SAS Proc Mixed, with REML estimation method 
and Kenward-Roger degrees of freedom algorithm.
8.2. Statistical Analyses
8.2.1. Extent of Excretion (Period 1)
Radioactivity excreted in urine and/or feces will be reported as the percentage of the
administered radioactivity excreted at each time interval, cumulatively through that interval
and the total percent of dose recovered in urine and/or feces.
Percent recovery and cumulative recovery of total radioactivity in urine, feces and emesis
(if any) will be determined based on total administered dose.
Individual participant and median data profiles will be graphically presented for the
cumulative recovery of radioactivity in emesis, urine, feces and their combination. The total
recovery of radioactivity in urine, feces and their combination will be listed and summarized
using descriptive statistics. Where possible, the rate of excretion of radioactivity will be
estimated.
Results of the extent of excretion analysis (ie, radioactivity in plasma, urine, and feces, and 
emesis if observed) will be detailed in a separate report provided and will be summarized
within the Clinical Study Report (CSR).


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8.2.2. Metabolic Profiling/Identification (Period 1)
Plasma, urine and fecal samples will be analyzed for metabolites of PF-06865571. Major
metabolites of PF-06865571 in plasma, urine, and feces following oral dose of 
[14C] PF-06865571 will be identified if possible. Results of the metabolic profiling analysis 
will be detailed in a separate report and will be summarized within the CSR.
8.2.3. Pharmacokinetic Analysis
The PK parameters detailed in Section 6.3 will be listed and summarized for participants in 
the appropriate analysis sets (as defined in Section 5.3).  Missing values will be handled as 
detailed in Section 7.
8.2.3.1. Plasma
The PF-06865571 PK parameters following a single dose administration of unlabeled 
PF-06865571 (oral) and microtracer dose of [14C] PF-06865571 (oral and IV) will be 
derived, where appropriate, from the concentration-time profiles as outlined below:

Parameters for total 14C (14C oral microtracer) will be derived for Period 1 only;

Parameters for PF-06865571 after oral doses of 14C oral microtracer and unlabeled
PF-06865571 for Periods 1 and 2, respectively and for [14C] PF-06865571 after 
14C IV microtracer for Period 2 will be derived.
Plasma PK parameters above will be listed and summarized descriptively by analyte (total
14C, unlabeled PF-06865571, and [14C] PF-06865571) and treatment, as applicable.
8.2.3.2. Absolute Oral Bioavailability (F)
F will be estimated as the ratio of adjusted geometric means of dose-normalized AUCinf (if
data permit, otherwise AUClast) for oral unlabeled PF-06865571 and IV labeled.
14C-PF-06865571 in plasma (from Period 2 only) which is equivalent to the following
equation:
F = [PF-06865571_AUCpo/ [14C] PF-06865571_AUCiv] × [[14C] PF-06865571_Doseiv/
PF-06865571_Dosepo]
Geometric mean ratio and 90% confidence interval: Natural log transformed AUCinf(dn) (if 
data permit) and AUClast(dn) from Period 2 will be analyzed using a mixed effect model with 
treatment as a fixed effect and participant as a random effect. Estimates of the adjusted
(least squares) mean differences (Test-Reference) and the corresponding 90% CI will be 
obtained from the model. The adjusted mean differences and 90% Cis for the differences will 
be exponentiated to provide estimates of the ratio of adjusted geometric means 
(Test/Reference) and 90% CI for the ratio. IV [14C] PF-06865571 is the Reference 
formulation and unlabeled oral PF-06865571 is the Test formulation.


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8.2.3.3. Fraction Absorbed (Fa)
8.2.3.3.1. Urine Parameters
Following urine parameters will be calculated following single dose administration of a
microtracer dose of [14C] PF-06865571 (oral and IV administration). Residual 14C levels
from Period 1 will be accounted for using an appropriate method, based on AMS principles
and methodology.
Parameter
Definition
Method of Determination
Total 14C_Urine_PO
Total radioactivity excreted into the 
urine postdose following oral 
administration of [14C]PF-06865571 
microtracer dose
Sum of [14C urine 
concentration × sample
volume] for each collection 
interval
Total 14C_Urine_IV
Total radioactivity excreted into the 
urine following IV administration of
[14C]PF-06865571 microtracer dose
Sum of [14C urine 
concentration × sample
volume] for each collection 
interval
%14C_Urine_PO
Percent of the radioactive dose 
administered that is excreted in the 
urine following oral administration
Total 14C_Urine_PO/14C 
Dosepo × 100
Where 14C Dosepo is the 
dose of 14C following oral 
administration of
[14C]PF-06865571
%14C_Urine_IV
Percent of the radioactive dose 
administered that is excreted in the 
urine following IV administration
Total 14C _Urine_IV/14C 
Doseiv × 100 Where 14C
Doseiv is the dose of 14C
following IV administration 
of [14C]PF-06865571
Total urine 14C amounts, percent 14C dose will be listed by treatment (oral in Period 1 and IV
in Period 2) and summarized using descriptive statistics.
8.2.3.3.2. Calculation of Fa
Fa will be estimated as the ratio of the adjusted geometric means of % of administered
radioactive dose excreted into the urine following oral and IV administration of
[14C]PF-06865571 microtracer dose over the same collection time (up to 48 hours post dose)
in Periods 1 and 2, respectively:
Fa = [% 14C_Urine_PO/% 14C_Urine_IV]


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PFIZER CONFIDENTIAL
Geometric mean ratio and 90% confidence interval: Natural log transformed % Total 14C in 
Urine from Period 1 and Period 2 will be analyzed using a mixed effect model with treatment 
as a fixed effect and participant as a random effect. Estimates of the adjusted (least squares) 
mean differences (Test-Reference) and the corresponding 90% CI will be obtained from the 
model. The adjusted mean differences and 90% CIs for the differences will be exponentiated 
to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CI 
for the ratio. Total 14C_Urine_IV is the Reference formulation and Total 14C_Urine_PO is 
the Test formulation.
Theoretically Fa would be expected to be greater than F. In the event that F is estimated to 
be greater than Fa, the greater of the 2 values will be used to represent the fraction of
PF-06865571 absorbed. PF-06865571 will be considered highly permeable if either F or Fa
is greater than 0.85.
PK parameters will be summarized by treatment and analyte as specified in Table 2. 
Table 2.
PK Parameters to be Summarized Descriptively
Matrix
Parameter
Summary Statistics
Plasma
AUClast, AUClast(dn), AUCinf, AUCinf(dn), 
Cmax, Cmax(dn), F, [CL/F (oral) or 
CL (IV)] and [VZ/F (oral) or Vss (IV)]
N, arithmetic mean, median, 
cv%, standard deviation, 
minimum, maximum, geometric 
mean and geometric cv%.
Plasma
Tmax
N, median, minimum, 
maximum.
Plasma
t1/2
N, arithmetic mean, median, 
cv%, standard deviation, 
minimum, maximum.
Urine
Total 14C Urine PO, Total 14C Urine IV, 
% 14C Urine PO, % 14C Urine IV, Fa
N, arithmetic mean, median, 
cv%, standard deviation, 
minimum, maximum.
Box and whisker plots for individual participant parameters (AUCinf(dn), AUClast(dn), 
Cmax(dn), % 14C urine PO, and % 14C urine IV) be presented and overlaid with geometric 
means.
Supporting data from the estimation of t½, and AUCinf will be listed by analyte: 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.


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Presentations for PK (plasma, where possible) concentrations by analyte will include:

A listing of all concentrations sorted by participant id and nominal time postdose for 
each analyte, route of administration and treatment, separately.  The listing of 
concentrations will include the actual times.  Deviations from the nominal time will 
be given in a separate listing.  

A summary of concentrations by nominal time postdose (produced separately for 
each analyte), where the set of statistics will include n, mean, median, standard 
deviation, coefficient of variation (cv), minimum, maximum and the number of 
concentrations above the lower limit of quantification.  

A plot (on both linear and semi-log scales) of median PK and radioactivity 
concentrations against nominal time postdose (based on the summary of 
concentrations by time postdose), where the median concentration-time profiles for 
plasma PF-06865571 PK (Period 1), and plasma radioactivity (Period 1) will be 
presented together on the same plot. 

A plot (on both linear and semi-log scales) of median PK and radioactivity 
concentrations against nominal time postdose (based on the summary of 
concentrations by time postdose), where the median concentration-time profiles for 
plasma PF-06865571 PK (Period 2), and plasma [14C] PF-06865571 (Period 2) will 
be presented together on the same plot where both have been dose-normalized 
(by oral and IV dose, respectively).  The dose-normalization will be calculated by 
programming using raw concentrations and the actual doses administered.

Plots (on both linear and semi-log scales) of individual concentrations against actual 
time postdose by participant. Concentration time plots for analytes PF-06865571
(Period 1) and total radioactivity (Period 1) will be presented together on the same 
plot. In a separate figure, the analytes PF-06865571 (Period 2) and 
[14C]PF-06865571 (Period 2), where both have been dose-normalized (by 
programming using raw concentrations and the actual doses administered), will be 
presented together on the same plot.
For summary statistics, median and 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.
8.3. Safety Analysis
A set of summary tables will be produced to evaluate any potential risk associated with the 
safety and toleration of administering PF-06865571.


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8.3.1. Treatment and Disposition of Participants
Participant evaluation groups will show end of study participant disposition and will show 
which participants were analyzed for pharmacokinetics, as well as for safety (adverse events 
and laboratory data).  Frequency counts will be supplied for participant discontinuation(s).
Data will be reported in accordance with the sponsor reporting standards.
8.3.2. Demographic and Clinical Examination Data
A break-down of demographic data will be provided for age, race, weight, body mass index, 
and height.  Each will be summarized as ‘All Participants’ in accordance with the sponsor 
reporting standards.
8.3.3. Discontinuation(s)
Participant discontinuations, and/or temporary discontinuations due to adverse events will be 
detailed and summarized.
Data will be reported in accordance with the sponsor reporting standards.
8.3.4. Adverse Events
Adverse events will be reported in accordance with the sponsor reporting standards.
8.3.5. Laboratory Data
The baseline measurement is the last predose measurement taken prior Period 1, Day 1 dose.
Laboratory data will be summarized and listed in accordance with the sponsor reporting 
standards.
8.3.6. Vital Signs Data
Vital Signs data will be databased and available upon request.
8.3.7. ECG Data
ECG data will be databased and available upon request.
8.3.8. Other Safety Data
None.
8.3.9. Concomitant Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the 
listings.


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8.3.10. Screening and Other Special Purpose Data
All the screening data will not be brought in-house, and therefore will not be listed.
 
 
8.3.12. Banked Bio-specimen data
Pharmacogenomic or biomarker data from Banked Biospecimens may be collected during or
after the trial and retained for future analyses; the results of such analyses are not planned 
to be included in the CSR.
9. REFERENCES
None.
CCI


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10. APPENDICES
Appendix 1. SAS CODE FOR ANALYSES
An example of the PROC MIXED code for Plasma data analysis is provided below:
proc mixed data=tab.pk;
class trt participant;
model l&var= trt/ ddfm=KR;
random participant /participant=participant;
lsmeans trt;
estimate 'Test vs Reference' trt -1  1  /cl alpha=0.1;
ods 'Estimates' out=est&var;
ods 'lsmeans' out=ls&var;
ods 'covparms' out=cov&var;
ods 'tests3' out=tst&var;
run;
/* Letter assignments for treatments (trt) within the estimate statement above are as follows;
For F:
A = Reference = IV 14C-PF-06865571
B = Test          = oral PF-06865571
For Fa:
A = Reference = Total 14C_Urine_IV
B = Test          = Total 14C_Urine_PO
*/;