Clinical trial NCT05580003
Conditions: Healthy
Keywords: Oral Antiviral COVID-19 Protease Inhibitor Mpro PF-07817883
Sponsor: Pfizer
Start date: 2022-10-17; Completion date: 2023-09-15
Enrollment: 94 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this clinical trial is to learn if the study medicine (called PF-07817883) is safe and how it goes in and out of the body in healthy people. PF-07817883 is for the potential treatment of COVID-19. Participants will take PF-07817883 by mouth up to 2 times a day. This study may also evaluate how much PF-07817883 gets into the body when taken as pill. We may study if people's diets can affect this study medicine. We may also examine how PF-07817883 is processed and removed by the human body. Finally, we may look into if PF-07817883 has potential to interact with midazolam.

Detailed description:
Combined 6-part study. Part-1: Single Ascending dose Part-2: Multiple Ascending Dose Part-3: Relative bioavailability and food effect Part-4: Metabolism and Excretion Part-5: Drug-drug interaction with midazolam Part-6: Supratherapeutic exposure Part-1,2 and 6 are double blind, sponsor open and Part-3,4 and 5 are open label study.

Arms: arm 1: None arm 2: None arm 3: None arm 4: None arm 5: Optional dose levels arm 6: Optional dose levels arm 7: A single dose of placebo arm 8: DR=Dosing regimen; twice a day arm 9: None arm 10: Optional dosing regimen arm 11: Optional dosing regimen arm 12: Optional dosing regimen to be studied in Japanese population arm 13: Optional dosing regimen to be studied in Chinese population arm 14: None arm 15: PART-3 is optional arm 16: First solid oral formulation (FORM1) arm 17: Second solid oral formulations (FORM-2) is optional arm 18: None arm 19: None arm 20: PART-4 is optional arm 21: Single dose of 5 mg alone arm 22: Single dose of 5 mg on Day 10 with multiple doses (twice a day) of PF-07817883 arm 23: A single dose at supratherapeutic exposure administered as divided doses (1h apart) arm 24: A single dose of placebo administered as divided doses (1h apart) arm 25: Moxifloxacin 400 mg at 0h followed by placebo at 1h
Interventions: intervention 1: PF-07817883 intervention 2: Placebo intervention 3: Midazolam intervention 4: Moxifloxacin
Intervention descriptions: intervention 1: Oral suspension or solid oral formulation(s) intervention 2: Placebo suspension intervention 3: midazolam oral solution intervention 4: Moxifloxacin 400 mg tablet

Protocol documents:
Prot_000.pdf: 
PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 1
COVID-19: A MULTIPART, PHASE 1 STUDY WITH RANDOMIZED,
DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE- AND 
MULTIPLE-DOSE ESCALATION TO EVALUATE THE SAFETY, 
TOLERABILITY AND PHARMACOKINETICS OF PF-07817883 AND OPTIONAL 
OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE RELATIVE 
BIOAVAILABILITY AND FOOD EFFECT OF SOLID ORAL FORMULATION
AND OPTIONAL OPEN-LABEL, NON-RANDOMIZED STUDY TO EVALUATE 
METABOLISM AND EXCRETION OF PF-07817883 AND OPTIONAL 
RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE EFFECT OF PF-07817883 
ON PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY ADULT 
PARTICIPANTS
Study Intervention Number:
PF-07817883
Study Intervention Name:
NA
US IND Number:
162644
EudraCT Number:
2022-002871-12
ClinicalTrials.gov ID:  
NCT05580003
Pediatric Investigational Plan Number:
NA
Protocol Number:
C5091001
Phase:
Phase 1
Sponsor Legal Address:
Pfizer Inc.
66 Hudson Boulevard East
New York, NY 10001
Brief Title: A Multipart Phase 1 Study Including Single Ascending Dose, Multiple 
Ascending Dose, Relative Bioavailability, Food Effect, Metabolism and Excretion And 
Drug-Drug Interaction of PF-07817883 in Healthy Adult Participants
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
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Document History
Document
Version Date
Amendment 3
09 March 2023
Amendment 2
31 January 2023
Amendment 1
21 October 2022
Original protocol
14 September 2022
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any global protocol administrative 
change letter(s).
Protocol Amendment Summary of Changes Table
Amendment 3 (09 March 2023)
Overall Rationale for the Amendment: To include stopping criteria for sentinel dosing, 
increase sample size as well as for safety review of PART-6 as per comments received from 
FDA.
Section # and 
Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 1.1 
Synopsis
Updated number of 
participants in PART-6 
and in the overall study.
Updated the statistical 
method for sample size 
justification.
To align the synopsis 
with the remainder of 
the protocol.
Substantial
Section 4.1.6 
PART-6: SE
Stopping criteria for 
sentinel dosing as well as 
for safety review of 
PART-6 were added.
Sample size was increased 
to 24 (4 in each of the 
6 sequences) to improve 
power of demonstrating
assay sensitivity.
To address comments
received from FDA.
Substantial
Section 7.4 
Stopping 
Criteria for 
PART-6: SE
Stopping criteria for 
sentinel dosing as well as 
for safety review of 
PART-6 were added.
To address comments
received from FDA.
Substantial
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Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
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Section # and 
Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 9.5 
Sample Size 
Determinatio;
Section 9.5.6 
PART-6:SE
Sample size was increased 
to 24 to improve power of 
demonstrating assay 
sensitivity. 
To address comments
received from FDA.
Substantial
Section 1.3.6. 
PART-6: SE
Notes in SoA (Table 9) 
were updated to clarify 
that contraception check 
and pregnancy test on 
Day -1 are scheduled for 
Period 1 only.
Clarification
Nonsubstantial
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Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
1. PROTOCOL SUMMARY...................................................................................................13
1.1. Synopsis ..................................................................................................................13
1.2. Schema ....................................................................................................................23
1.2.1. PART-1: SAD.............................................................................................23
1.2.2. PART-2: MAD ...........................................................................................24
1.2.3. PART-3: RBA/FE.......................................................................................25
1.2.4. PART-4: ME...............................................................................................26
1.2.5. PART-5: DDI..............................................................................................26
1.2.6. PART-6: SE................................................................................................27
1.3. Schedule of Activities .............................................................................................28
1.3.1. PART-1: SAD.............................................................................................28
1.3.2. PART-2: MAD ...........................................................................................32
1.3.3. PART-3: RBA/FE.......................................................................................35
1.3.4. PART-4: ME...............................................................................................38
1.3.5. PART-5: DDI..............................................................................................40
1.3.6. PART-6: SE................................................................................................49
2. INTRODUCTION ...............................................................................................................53
2.1. Study Rationale .......................................................................................................53
2.2. Background .............................................................................................................53
2.2.1. Nonclinical Overview.................................................................................54
2.2.1.1. Nonclinical Pharmacology........................................................54
2.2.1.2. Biopharmaceutics and Nonclinical PK .....................................55
2.2.1.3. Toxicology of PF-07817883 .....................................................56
2.2.2. Clinical Overview.......................................................................................57
2.2.2.1. Safety Overview........................................................................57
2.2.2.2. Summary of PF-07817883 PK in Human .................................57
2.3. Benefit/Risk Assessment.........................................................................................59
2.3.1. Risk Assessment.........................................................................................60
2.3.2. Benefit Assessment.....................................................................................64
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Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
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2.3.3. Overall Benefit/Risk Conclusion................................................................64
3. OBJECTIVES AND ENDPOINTS.....................................................................................64
3.1. PART-1: SAD .........................................................................................................64
3.2. PART-2: MAD (including optional Japanese and Chinese Cohort).......................65
3.3. PART-3: RBA/FE ...................................................................................................65
3.4. PART-4: ME ...........................................................................................................66
3.5. PART-5: DDI..........................................................................................................66
3.6. PART-6: SE.............................................................................................................67
4. STUDY DESIGN.................................................................................................................68
4.1. Overall Design.........................................................................................................68
4.1.1. PART-1: SAD.............................................................................................69
4.1.2. PART-2: MAD ...........................................................................................70
4.1.3. PART-3: RBA/FE.......................................................................................71
4.1.4. PART-4: ME...............................................................................................72
4.1.5. PART-5: DDI..............................................................................................72
4.1.6. PART-6: SE................................................................................................73
4.2. Scientific Rationale for Study Design.....................................................................74
4.2.1. PART-1: SAD.............................................................................................74
4.2.2. PART-2: MAD ...........................................................................................75
4.2.3. PART-3: RBA/FE.......................................................................................75
4.2.4. PART-4: ME...............................................................................................75
4.2.5. PART-5: DDI..............................................................................................76
4.2.6. PART-6: SE................................................................................................76
4.2.7. Choice of Contraception/Barrier Requirements .........................................77
4.2.8. Collection of Retained Research Samples..................................................77
4.3. Justification for Dose ..............................................................................................77
4.3.1. Justification of Dose for PART-1 to PART-5 (Original Protocol, 14 
September 2022)..............................................................................................77
4.3.2. Justification of Dose for PART-3:RBA/FE................................................80
4.3.3. Justification of Dose for PART-6:SE (Protocol Amendment 2, 31 
January 2023)...................................................................................................81
4.4. End of Study Definition ..........................................................................................81
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Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
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5. STUDY POPULATION......................................................................................................81
5.1. Inclusion Criteria.....................................................................................................82
5.2. Exclusion Criteria....................................................................................................83
5.3. Lifestyle Considerations..........................................................................................86
5.3.1. Contraception..............................................................................................86
5.3.2. Meals and Dietary Restrictions...................................................................86
5.3.2.1. Dietary Fiber Supplementation (PART-1 and PART-4 
only)...................................................................................................88
5.3.3. Caffeine, Alcohol, and Tobacco .................................................................89
5.3.4. Activity .......................................................................................................89
5.4. Screen Failures ........................................................................................................89
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................90
6.1. Study Intervention(s) Administered........................................................................90
6.1.1. Administration............................................................................................91
6.1.1.1. PART-1:SAD ............................................................................91
6.1.1.2. PART-2:MAD...........................................................................92
6.1.1.3. PART-3: RBA/FE .....................................................................92
6.1.1.4. PART-4: ME .............................................................................92
6.1.1.5. PART-5: DDI............................................................................92
6.1.1.6. PART-6: SE...............................................................................93
6.2. Preparation, Handling, Storage, and Accountability...............................................93
6.2.1. Preparation and Dispensing........................................................................94
6.3. Assignment to Study Intervention...........................................................................95
6.4. Blinding...................................................................................................................95
6.4.1. Blinding of Participants..............................................................................96
6.4.2. Blinding of Site Personnel..........................................................................96
6.4.3. Blinding of the Sponsor..............................................................................96
6.4.4. Breaking the Blind......................................................................................96
6.5. Study Intervention Compliance...............................................................................97
6.6. Dose Modification...................................................................................................97
6.6.1. Dose Escalation and Stopping Rules..........................................................97
6.7. Continued Access to Study Intervention After the End of the Study......................99
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6.8. Treatment of Overdose............................................................................................99
6.9. Prior and Concomitant Therapy ..............................................................................99
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL.........................................................................100
7.1. Discontinuation of Study Intervention ..................................................................100
7.1.1. ECG Changes............................................................................................100
7.1.2. Potential Cases of Acute Kidney Injury ...................................................100
7.1.3. COVID-19 ................................................................................................101
7.2. Participant Discontinuation/Withdrawal From the Study.....................................101
7.2.1. Withdrawal of Consent.............................................................................102
7.3. Lost to Follow-up..................................................................................................102
7.4. Stopping Criteria for PART-6:SE .........................................................................103
7.4.1. Stopping Criteria for Sentinel Dosing: .....................................................103
7.4.2. Stopping Criteria Following Evaluation of Safety Data from the First 
6 Participants (Periods 1 to 3) in PART-6:SE ...............................................103
8. STUDY ASSESSMENTS AND PROCEDURES.............................................................104
8.1. Administrative and Baseline Procedures...............................................................104
8.1.1. Baseline Procedures..................................................................................105
8.1.1.1. Medical History.......................................................................105
8.1.1.2. Demographics..........................................................................106
8.2. Efficacy Assessments............................................................................................106
8.3. Safety Assessments ...............................................................................................106
8.3.1. Physical Examinations..............................................................................106
8.3.2. Vital Signs ................................................................................................106
8.3.2.1. Blood Pressure and Pulse Rate................................................106
8.3.2.2. Respiratory Rate......................................................................107
8.3.3. Electrocardiograms...................................................................................107
8.3.3.1. Continuous Cardiac Monitoring by Telemetry (PART-1 
and PART-6 only) ...........................................................................108
8.3.4. Clinical Safety Laboratory Assessments ..................................................109
8.3.4.1. Alternative Facilities for Clinical Safety Laboratory 
Assessment ......................................................................................109
8.3.5. COVID-19 Specific Assessments.............................................................109
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8.3.6. Pregnancy Testing ....................................................................................109
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting ...............110
8.4.1. Time Period and Frequency for Collecting AE and SAE Information.....110
8.4.1.1. Reporting SAEs to Pfizer Safety.............................................111
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF.................111
8.4.2. Method of Detecting AEs and SAEs ........................................................111
8.4.3. Follow-Up of AEs and SAEs....................................................................112
8.4.4. Regulatory Reporting Requirements for SAEs.........................................112
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure...................................................112
8.4.5.1. Exposure During Pregnancy....................................................113
8.4.5.2. Exposure During Breastfeeding ..............................................114
8.4.5.3. Occupational Exposure ...........................................................115
8.4.6. Cardiovascular and Death Events.............................................................115
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs............................................................................115
8.4.8. Adverse Events of Special Interest...........................................................115
8.4.8.1. Lack of Efficacy......................................................................115
8.4.9. Medical Device Deficiencies....................................................................115
8.4.10. Medication Errors...................................................................................115
8.5. PK..........................................................................................................................116
8.5.1. Plasma for Analysis of PF-07817883 PK, Total Drug-Related 
Material Measurement, and Metabolic Profiling...........................................116
8.5.2. Plasma for PK Analysis of Midazolam (PART-5: DDI only)..................118
8.5.3. Plasma for PK Analysis of Moxifloxacin (PART-6: SE only).................119
8.5.4. Plasma for the Measurement of PK Biomarkers (PART-2) .....................120
8.5.5. Urine PK (PART-2 only)..........................................................................120
8.5.6. Urine and Feces for Measurement of Drug-Related Material and 
Metabolic Profiling (PART-1 and PART-4)..................................................121
8.6. Genetics.................................................................................................................121
8.6.1. Specified Genetics ....................................................................................121
8.6.2. Retained Research Samples for Genetics .................................................121
8.7. Biomarkers ............................................................................................................122
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8.7.1. Specified Gene Expression (RNA) Research ...........................................122
8.7.2. Specified Protein Research.......................................................................122
8.7.3. Specified Metabolomic Research .............................................................122
8.7.4. Retained Research Samples for Biomarkers.............................................122
8.8. Immunogenicity Assessments...............................................................................122
8.9. Health Economics .................................................................................................122
8.10. Taste Assessment of PF-07817883 (PART-3 only)............................................122
9. STATISTICAL CONSIDERATIONS ..............................................................................122
9.1. Statistical Hypotheses ...........................................................................................122
9.2. Analysis Sets .........................................................................................................123
9.3. Statistical Analyses ...............................................................................................123
9.3.1. General Considerations.............................................................................124
9.3.2. Primary Endpoint(s) Analysis...................................................................124
9.3.3. Secondary Endpoint(s) Analysis...............................................................124
9.3.3.1. PK Analysis.............................................................................124
9.3.3.2. Statistical Methods for PK Data..............................................126
9.3.4. Tertiary/Exploratory Endpoint(s) Analysis ..............................................128
9.3.5. Safety Analyses ........................................................................................128
9.3.5.1. Electrocardiogram Analyses....................................................128
9.3.6. Other Analyses..........................................................................................129
9.3.6.1. Taste Assessment ....................................................................129
9.3.6.2. Pharmacogenomic/Biomarker Assessment.............................129
9.4. Interim Analyses ...................................................................................................129
9.5. Sample Size Determination...................................................................................129
9.5.1. PART-1: SAD...........................................................................................130
9.5.2. PART-2: MAD .........................................................................................130
9.5.3. PART-3: RBA/FE.....................................................................................130
9.5.4. PART-4: ME.............................................................................................131
9.5.5. PART-5: DDI............................................................................................131
9.5.6. PART-6: SE..............................................................................................131
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................133
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10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............133
10.1.1. Regulatory and Ethical Considerations ..................................................133
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................133
10.1.2. Informed Consent Process ......................................................................134
10.1.3. Data Protection .......................................................................................135
10.1.4. Committees Structure .............................................................................135
10.1.4.1. Data Monitoring Committee .................................................135
10.1.5. Dissemination of Clinical Study Data ....................................................135
10.1.6. Data Quality Assurance ..........................................................................136
10.1.7. Source Documents..................................................................................138
10.1.8. Study and Site Start and Closure ............................................................138
10.1.9. Sponsor’s Medically Qualified Individual..............................................139
10.2. Appendix 2: Clinical Laboratory Tests ...............................................................140
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ...................................................................141
10.3.1. Definition of AE .....................................................................................141
10.3.2. Definition of an SAE ..............................................................................142
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period..........................................................................143
10.3.4. Reporting of SAEs..................................................................................147
10.4. Appendix 4: Contraceptive and Barrier Guidance ..............................................148
10.4.1. Male Participant Reproductive Inclusion Criteria..................................148
10.4.2. Female Participant Reproductive Inclusion Criteria...............................148
10.4.3. Woman of Childbearing Potential ..........................................................149
10.4.4. Contraception Methods...........................................................................150
10.5. Appendix 5: Genetics..........................................................................................152
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .....153
10.7. Appendix 7: Kidney Safety: Monitoring Guidelines ..........................................155
10.7.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury............................................................................155
10.7.2. Age-Specific Kidney Function Calculation Recommendations.............155
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10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI 
Equations.........................................................................................155
10.7.3. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities.................................................................................................155
10.8. Appendix 8: ECG Findings of Potential Clinical Concern .................................156
10.10. Appendix 10: Abbreviations .............................................................................168
10.11. Appendix 11: Protocol Amendment History.....................................................173
11. REFERENCES ................................................................................................................178
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Protocol C5091001
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LIST OF TABLES
Table 1.
PART-1: SAD Cohorts.............................................................................28
Table 2.
PART-2: MAD Cohorts (Including Optional Japanese and Chinese 
Cohorts) ....................................................................................................32
Table 3.
PART-2: PK Days (Day 1, Day 5, Day 10) in MAD Cohorts 
(Including Optional Japanese and Chinese Cohorts)................................34
Table 4.
PART-3: RBA/FE Cohort.........................................................................35
Table 5.
PART-4: ME Cohort.................................................................................38
Table 6.
PART-5: DDI for Sequence 1...................................................................40
Table 7.
PART-5: DDI for Sequence 2...................................................................44
Table 8.
PART-5: PK Days (Day 1, Day 5, Day 10) in Treatment B ....................47
Table 9.
PART-6: SE..............................................................................................49
Table 10.
Summary of Preliminary (Unaudited) Plasma and Urine PK 
Parameters of PF-07817883 Following Multiple Oral Dose 
Administration of PF-07817883 for 10 Days in Healthy Participants 
in PART-2 of Study C5091001 ................................................................58
Table 11.
Provisional Dosing Scheme in PART-1: SAD.........................................70
Table 12.
Treatment Sequences in PART-3: RBA/FE .............................................71
Table 13.
Treatment Sequences in PART-5: DDI....................................................73
Table 14. 
Treatment Sequences in PART-6: SE.......................................................74
Table 15.
Predicted Human Exposure and Safety Margins of PF-07817883 
Relative to Exposure Limits at Planned Dose Levels in SAD..................79
Table 16.
Predicted Human Exposure and Safety Margins of PF-07817883 
Relative to Exposure Limits at Planned Dose Levels in MAD ................80
Table 17.
Plasma PF-07817883 PK Parameters for PART-1: SAD, PART-3: 
RBA/FE, PART-4: ME and PART-6: SE, Midazolam PK 
Parameters in PART-5: DDI, and Moxifloxacin PK Parameters in 
PART-6: SE............................................................................................124
Table 18.
Plasma and Urine PF-07817883 PK Parameters for PART-2: MAD 
and PART-5: DDI...................................................................................126
Table 19.
Expected Widths of the 90% CIs (with 80% Coverage Probability) 
for Different Possible Estimated Effects for AUClast, Cmax and 
AUCinf.....................................................................................................130
Table 20.
Expected Widths of the 90% CIs (with 80% Coverage Probability) 
for Different Possible Estimated Effects for AUCinf ..............................131
Table 21.
Protocol-Required Safety Laboratory Assessments ...............................140
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title:
COVID-19: A Multipart, Phase 1 Study with Randomized, Double Blind, Sponsor-Open, 
Placebo-Controlled, Single- and Multiple-Dose Escalation to Evaluate the Safety, 
Tolerability and Pharmacokinetics of PF-07817883 and Optional Open-Label, Randomized 
Study to Evaluate Relative Bioavailability and Food Effect of Solid Oral Formulation and 
Optional Open-Label, Non Randomized Study to Evaluate Metabolism and Excretion of PF
07817883 and Optional Randomized, Open-Label Study to Assess the Effect of PF 07817883 
on Pharmacokinetics of Midazolam in Healthy Adult Participants.
Brief Title:
A Multipart Phase 1 Study Including Single Ascending Dose, Multiple Ascending Dose, 
Relative Bioavailability, Food Effect, Metabolism and Excretion and Drug-Drug Interaction
of PF-07817883 in Healthy Adult Participants.
Regulatory Agency Identification Number(s):
US IND Number:
162644
EudraCT Number:
2022-002871-12
ClinicalTrials.gov ID:  
NCT05580003
Pediatric Investigational Plan Number:
NA
Protocol Number:
C5091001
Phase:
Phase 1
Rationale:
The current study is the FIH study of PF-07817883 in healthy adult participants. It is a 6-part 
study combining PART-1: SAD, PART-2: MAD, PART-3: RBA/FE PART-4: ME, PART-
5: DDI, and PART-6: SE. PART-1 and PART-2 will evaluate safety, tolerability, and PK of 
single and multiple escalating oral doses of PF-07817883 in healthy adult participants, 
respectively. PART-2 of the study may also evaluate the safety, tolerability, and PK in 
Japanese and Chinese participants. PART-3 will evaluate RBA and FE of up to 2 new 
PF-07817883 oral formulations. PART-4 will evaluate the ME of PF-07817883. PART-5 
will evaluate the effect of steady-state PF-07817883 on PK of midazolam in healthy 
participants. PART-6 will assess the safety, tolerability, and PK of PF-07817883 at SE.
Results from this study will inform the study design of the Phase 2/3 studies in COVID-19 
patients.
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Objectives and Endpoints:
PART-1: SAD
Objectives
Endpoints
Primary: 
Primary: 
!
To assess the safety and tolerability following 
single ascending doses of PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
Secondary: 
Secondary: 
!
To assess the plasma PK profile of PF-07817883 
following single ascending doses of 
PF-07817883.
!
Plasma PK parameters of PF-07817883: 
!
Cmax, Tmax, AUClast, Cmax(dn), AUClast(dn).
!
If data permit, AUCinf, AUCinf(dn), t½, Vz/F, 
and CL/F. 
PART-2: MAD
Objectives
Endpoints
Primary: 
Primary: 
!
To assess the safety and tolerability following 
multiple ascending doses of PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
Secondary: 
Secondary: 
!
To assess the plasma PK profile of PF-07817883 
on Days 1, 5 and 10 following multiple 
ascending doses of PF-07817883.
!
Plasma PK parameters of PF-07817883: 
!
Cmax, Tmax, AUCtau, C12, Cmax(dn), 
AUCtau(dn), Cav, Rac, Rac,Cmax, PTR,CL/F 
and Vz/F.
!
If data permit, t½.
!
To assess the renal excretion of PF-07817883 on 
Day 10 following multiple ascending doses of 
PF-07817883.
!
PF-07817883 urinary PK parameters: 
!
Aetau and Aetau%, CLr.
PART-3: RBA/FE
Objectives
Endpoints
Primary: 
Primary: 
!
To determine the oral bioavailability of oral 
formulation(s) of PF-07817883 relative to 
suspension. 
!
The ratio of AUClast, AUCinf and Cmax of oral 
formulation(s) and suspension.
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Protocol C5091001
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Objectives
Endpoints
Secondary: 
Secondary: 
!
To evaluate the effect of food (high-fat 
high-calorie meal) on the exposure of 
PF-07817883 following a single oral dose of 
PF-07817883 tablet formulation(s).
!
The ratio of AUClast, AUCinf and Cmax of tablet 
formulation under fed condition and fasted 
condition.
!
To determine the PK of PF-07817883 following 
oral administration of tablet formulation(s) and 
suspension of PF-07817883.
!
Plasma PK parameters of PF-07817883: Tmax,
Cmax, AUClast, if data permit AUCinf, t½, CL/F, 
Vz/F. 
!
To determine the safety and tolerability of 
PF-07817883 following oral administration of 
tablet formulation(s) and suspension of 
PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
PART-4: ME
Objectives
Endpoints
Primary: 
Primary: 
!
To determine the extent of excretion of drug-
related material in urine and feces after a single 
oral administration of PF-07817883.
!
Total recovery of drug-related material in urine 
and feces separately, and both routes combined, 
expressed as a percent of total dose 
administered.
Secondary: 
Secondary: 
!
To determine the PK of PF-07817883 following 
a single oral administration of PF-07817883.
!
Plasma PK parameters of PF-07817883: Tmax, 
Cmax, AUClast, if data permit AUCinf, t½, CL/F, 
Vz/F. 
!
To determine the safety and tolerability of 
PF-07817883 after a single oral administration 
of PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
PART-5: DDI
Objectives
Endpoints
Primary Objective: 
Primary Endpoint: 
!
To estimate the effect of PF-07817883 on the PK
of midazolam.
!
Midazolam plasma PK parameters: Cmax and 
AUCinf (if data permit, otherwise AUClast) with 
PF-07817883 (test) versus without 
PF-07817883 (reference).
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Objectives
Endpoints
Secondary Objective: 
Secondary Endpoints: 
!
To evaluate the safety and tolerability of 
PF-07817883 in healthy participants in the 
absence and presence of midazolam.
!
To evaluate the effects of PF-07817883 on 
additional PK parameters of midazolam in 
healthy participants.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
!
Midazolam plasma PK parameters: Tmax, 
AUClast, and if data permit t½, CL/F, and Vz/F 
for midazolam with and without 
coadministration of PF-07817883.
PART-6: SE cohort
Objectives
Endpoints
Primary Objective: 
Primary Endpoint: 
!
To assess the safety and tolerability of a SE of 
PF-07817883 administered as split dosing.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
Secondary Objective: 
Secondary Endpoints: 
!
To assess the plasma PK of PF-07817883 at a 
SE of PF-07817883 administered as split dosing.
!
Plasma PK parameters of PF-07321332: 
!
Cmax, Tmax, AUClast
!
If data permit, AUCinf, t½.
Overall Design:
This 6-part, Phase 1, FIH study will combine PART-1: SAD, PART-2: MAD, including 
Japanese and Chinese cohorts, PART-3: RBA/FE cohort, PART-4: ME cohort, PART-5: 
DDI cohort, and PART-6: SE cohort. 
PART-1 and PART-2 are a randomized, double-blind, sponsor-open, placebo-controlled trial 
to evaluate safety, tolerability, and PK of single and multiple escalating oral doses of 
PF-07817883 in healthy adult participants, respectively. PART-2 of the study may also 
evaluate the safety, tolerability, and PK in Japanese and Chinese participants. PART-3 is a 
randomized, open-label, cross-over, study to evaluate RBA and FE of up to 2 new 
PF-07817883 oral formulations. PART-4 is an open-label, non-randomized, single period 
cohort to evaluate the ME of PF-07817883. PART-5 is an open-label, randomized, cross-
over cohort to evaluate the effect of steady-state PF-07817883 on PK of midazolam in 
healthy participants. PART-6 is a sponsor-open, randomized, 3-treatment, 3-period, 
6-sequence, cross-over, placebo-and positive-controlled study to evaluate safety, tolerability,
and PK of PF-07817883 at SE.  
PART-1: SAD
SAD will include 2 interleaving cohorts with a total of approximately 16 participants planned 
(approximately 8 participants in each cohort [6 active: 2 placebo]), with 3-period, cross-over 
in each cohort. Period 3 is an optional period which may be used to further explore PK at 
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additional doses or assess FE (high-fat high-calorie meal), based on emerging safety, 
tolerability, and PK assessments.
There will be a washout interval of ≥5 days between dosing to a given participant. 
Participants will be required to stay at the CRU for the duration of the washout interval.
However, they may be released at the discretion of the investigator. The washout interval 
may be adjusted based on data emerging from previous cohorts/periods. 
PART-2: MAD
The proposed MAD study design will be parallel cohorts, with 10 days of dosing. PART-2 
will consist of approximately 2 to 6 cohorts, including up to 4 optional cohorts (Cohorts 5, 6, 
7, and 8) with approximately 6 participants in each cohort (4 active: 2 placebo). Cohorts 7 
and 8 are optional Japanese and Chinese participants cohort, respectively.
PART-3: RBA/FE
This cohort will be an open-label, randomized, 4-period, 6-sequence cross-over SD cohort 
evaluating the RBA of 2 new PF-07817883 oral formulation(s) compared to PF-07817883 
oral suspension and to evaluate the effect of food on the bioavailability of the PF-07817883 
oral formulation(s) in healthy adult participants. Approximately 12 participants may be 
enrolled in PART-3 of the study with approximately equal number of participants 
randomized to each sequence. In this part, there will be a washout interval of at least 3 days 
between dosing to a given participant in each period.
PART-4: ME
This part will include a single cohort of approximately 6 male participants. The dose of this 
cohort will be decided based on the emerging PK and safety data and the selected dose will 
be less than or equal to a dose deemed safe and tolerable in PART-1. Each participant will 
receive a single dose of PF-07817883 at 0 hr on Day 1 after at least 10 hr of fasting. The 
participants will be discharged on Day 11.
PART-5: DDI 
This part may consist of up to 2 cohorts (Cohort 11 and optional Cohort 12). Each cohort
consists  of 2 treatments, 2 sequences, and 2 periods with a cross-over design to evaluate the 
effect of steady-state PF-07817883 on the PK of midazolam in healthy adult participants. The 
dose of PF-07817883 in Cohort 11 is 600 mg BID and the dose of Cohort 12 will be decided
based on the emerging PK data from Cohort 11. This part will consist of 2 treatments: single 
oral dose of 5 mg midazolam alone (Treatment A) and multiple oral doses of PF-07817883 in 
combination with a single oral dose of 5 mg midazolam (Treatment B). Each enrolled 
participant will be randomly assigned to 1 of 2 sequences to receive 2 treatments in 2
periods. In each cohort, a total of approximately 14 healthy participants will be enrolled to 
ensure at least 12 participants will complete this part. 
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PART-6: SE
This cohort will include approximately 24 adult healthy participants randomized to 3-period,
6-sequence, cross-over design to explore safety, tolerability, and PK at SE. The participants 
randomized to treatment will receive 6000 mg as 2 split doses of PF-07817883 3000 mg 
administered at 0 and 1 h. The participant randomized to placebo will receive placebo at 0 
and 1h. The participants randomized to moxifloxacin will receive moxifloxacin 400 mg and 
placebo at 0 and 1h, respectively. Sentinel dosing will be implemented in this cohort.
Treatment assignments to PF-07817883 and placebo will be blinded to the participants, 
investigator and CRU staff (except pharmacy staff) but open to the sponsor. Administration 
of moxifloxacin and placebo in participants randomized to moxifloxacin treatment will be 
open label.
Number of Participants:
A total of up to 122 participants (16 in PART-1: SAD, up to 36 [with 2 cohorts and 
4 optional cohorts] in PART-2: MAD, 12 in PART-3: RBA/FE cohort, 6 in PART-4: ME,  
up to 28 [with 2 cohorts of 14 each] in PART-5: DDI and 24 in PART-6: SE) are planned to 
be enrolled in this study.
Note: "Enrolled" means a participant's, agreement to participate in a clinical study following 
completion of the informed consent process and assignment to study intervention. A 
participant will be considered enrolled if the informed consent is not withdrawn prior to 
participating in any study activity. Potential participants who are screened for the purpose of 
determining eligibility for the study, but do not participate in the study, are not considered 
enrolled, unless otherwise specified by the protocol.
Study Population:
Key inclusion and exclusion criteria are listed below:
Inclusion Criteria 
Participants must meet the following key inclusion criteria to be eligible for enrollment into 
the study:
Age and Sex:
1. Participants, male or female, 18 to 60 years of age, inclusive, at the time of signing 
the ICD. Only Male participants will be included in PART-4. 
2. Male and female participants who are overtly healthy as determined by medical 
evaluation including medical history, PE, laboratory tests, and standard 12-lead ECG.
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Other Inclusion Criteria: 
3. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). A body weight 
of 45 kg may be considered in selected cases.
4. For optional Japanese/Chinese cohorts or PART-5 only: Japanese participants who 
have 4 Japanese biologic grandparents who were born in Japan. Chinese participants 
who were born in mainland China and both parents are of the Chinese descent.
5. Capable of giving signed informed consent, which includes compliance with the 
requirements and restrictions listed in the ICD and in this protocol.
Exclusion Criteria 
Participants with any of the following characteristics/conditions will be excluded:
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. 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 COVID-19 pandemic that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for 
the study.
3. Positive test result for SARS-CoV-2 infection at admission. 
Prior/Concomitant Therapy:
4. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 28 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. 
5. Participants who have received a COVID-19 vaccine within 7 days before screening 
or admission, or who are to be vaccinated with a COVID-19 vaccine at any time 
during the study confinement period.
Prior/Concurrent Clinical Study Experience:
6. Previous administration with an investigational product (drug or vaccine) within 
30 days (or as determined by the local requirement) or 5 halflives preceding the first 
dose of study intervention used in this study (whichever is longer).
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Diagnostic Assessments:
7. A positive urine drug test.
8. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at 
least 5 minutes of supine rest.
9. Renal impairment as defined by an eGFR in adults, of <75 mL/min. 
10. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results.
Other Exclusion Criteria:
11. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening.
12. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing. 
13. Use of tobacco or nicotine-containing products in excess of the equivalents of 
5 cigarettes per day or 2 chews of tobacco per day.
14. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members. 
15. Pregnant or breastfeeding women.
16. PART-6 Only: Participants who according to the product label for moxifloxacin, 
would be at increased risk if dosed with moxifloxacin (ie, including but not limited to 
participants with history of myasthenia gravis, tendinitis/tendon rupture).
17. PART-6 Only: History of hypersensitivity, allergy, severe adverse drug reaction or 
intolerance to quinolone antibiotics, including moxifloxacin.
Study Arms and Duration:
Study Intervention(s)
Intervention 
Name
PF-07817883
Placebo
Midazolam
Moxifloxacin
Arm Name
(group of 
participants 
receiving a 
specific 
treatment or no 
treatment)
PART-1 through 
PART-5
PART-1 and PART-2.
PART-5.
PART-6
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Study Intervention(s)
Type
Drug
Drug
Drug
Drug
Dose 
Formulation
Suspension/Solution 
or solid oral 
formulation (eg,
tablet)
Suspension/Solution or 
solid oral formulation 
(eg, tablet)
Solution.
Tablet
Unit Dose 
Strength(s)
Planned oral 
suspension/solution 
doses ranging from 
150 mg to 6000 mg.
Planned nominal 
solid oral 
formulation strength 
100-400 mg 
pending final 
formulation 
development and 
dose.
0 mg
As available locally.
As available locally.
Dosage Level(s)
Planned oral 
suspension/solution
doses ranging from 
150 mg to 6000 mg.
Planned nominal 
solid oral 
formulation strength 
100 - 400 mg 
pending final 
formulation 
development and 
dose.
0 mg
5 mg SD
400 mg
Route of 
Administration
Oral
Oral
Oral
Oral
Use
Experimental
Placebo
Probe substrate
Active control
IMP or 
NIMP/AxMP
IMP
IMP
NIMP
NIMP/AxMP
Sourcing
Provided centrally 
by the sponsor.
Provided centrally by the 
sponsor.
Provided locally by the 
CRU.
Provided locally by 
the CRU.
Packaging and 
Labeling
Materials (API and
components) for
extemporaneous 
prep of oral 
suspensions will be
provided in bulk.
Tablets will be 
provided in bulk. 
CRU staff will
prepare individual 
doses for 
administration.
Individual dose
containers will be
labeled by site staff
per country 
requirement.
Materials (API and
components) for
extemporaneous prep of
oral suspensions will be
provided in bulk.
Solid oral formulation
will be provided in bulk. 
CRU staff will prepare 
individual doses for 
administration.
Individual dose
containers will be
labeled by site staff per 
country requirement.
CRU will procure 
commercially labeled 
materials.
CRU will procure 
commercially labeled 
materials.
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Study Intervention(s)
Current/Former 
Name(s) or 
Alias(es)
PF-07817883
Placebo
As available locally.
As available locally.
Statistical Methods:
The sample size for PART-1 and PART-2 of the study has been chosen based on the need to
minimize exposure of healthy participants to a new chemical entity and the requirements to
provide adequate safety and toleration and PK information at each dose level.
For PART-3, a sample size of 12 participants will provide adequate precision to compare the 
RBA of up to 2 new oral formulation(s) of PF-07817883 relative to oral suspension.
For PART-4: A sample size of approximately 6 male participants (with at least 4 completers) 
is chosen based on the industry standard sample size for ME studies. This sample size was 
not justified by any empirical data or hypothesis testing criteria.
For PART-5: A sample size of 14 participants (with at least 12 completers) is chosen based 
on the need to provide sufficient precision to detect a 1.25-fold difference in Midazolam 
AUCinf.
For PART-6: A sample size of approximately 24 participants will provide at least 87% power 
to demonstrate assay sensitivity for C-QTc modeling with pre-dose baseline as reported in 
Huang et al (2021).
The data from the 6 parts of this study will be analyzed and reported separately in a single
CSR. Exploratory analyses may not be included within the CSR.
All safety analyses will be performed on the safety analysis set, which is defined as all
participants randomly assigned to study intervention and who receive at least 1 dose of study 
intervention. Participants will be analyzed according to the product they actually received. 
Safety data will be presented in tabular and/or graphical format and summarized
descriptively, where appropriate. 
For each part separately, plasma concentrations will be listed and summarized descriptively 
by PK sampling time and treatment. The plasma PK parameters and urine PK parameters 
(PART-2 only) of PF-07817883 and midazolam (PART-5 only), as applicable, will be
summarized descriptively by treatment. No formal inferential statistics will be applied to the 
plasma PK data apart from the comparisons of new oral formulation(s) and FE in either 
PART-1 or PART-3 and the estimation of the effect of PF-07817883 on the PK of 
midazolam in PART-5.
Ethical Considerations:
PF-07817883 is not expected to provide any clinical benefit to healthy participants. This 
study is designed primarily to generate safety, tolerability, and PK data for further clinical 
development.
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1.2. Schema
1.2.1. PART-1: SAD 
SAD dose levels D1 to D6 in Table 15 in Section 4.3.
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1.2.2. PART-2: MAD
MAD dosing regimens DR1 to DR4 are listed in Table 16 in Section 4.3.
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1.2.3. PART-3: RBA/FE
Cohort-9
Formulation 1: 
Formulation 2: 
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1.2.4. PART-4: ME
Cohort 10
1.2.5. PART-5: DDI 
Cohort 11
Cohort-12 (Optional)
Washout duration may be modified based on emerging data.
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1.2.6. PART-6: SE
Cohort-13
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
1.3.1. PART-1: SAD
Table 1.
PART-1: SAD Cohorts
Visit Identifier
Abbreviations used in this table 
may be found in Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Days
29-36
!
Follow-up to occur 28-35 days 
after administration of last
dose of study intervention via 
telephone contact.
Hours After Dose
0 0.25 0.5
1
1.5
2
4
6
8
12
16
24h
48h
72h
96h
120h
Informed consent
X
Inclusion/exclusion criteria
X
X
!
Not required in Period 2 and 
Period 3.
Demographics (including height 
& weight)
X
!
Refer to Section 8.1.1.2.
Medical/Medicine history 
X
X
!
Only required in Periods 2 and 
3 if discharged from the site.
SARS-CoV-2 RT-PCR
X
!
Only required in Periods 2 and 
3 if discharged from the site.
!
As per local CRU procedures.
COVID-19 signs and symptoms
X
X
!
As per local CRU procedures.
CRU Confinement
X
∀∀∀∀∀∀∀∀∀∀∀
∀
∀
∀
X
!
Participants remain confined 
until Day 5 in last period. 
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Table 1.
PART-1: SAD Cohorts
Visit Identifier
Abbreviations used in this table 
may be found in Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Days
29-36
!
Follow-up to occur 28-35 days 
after administration of last
dose of study intervention via 
telephone contact.
Hours After Dose
0 0.25 0.5
1
1.5
2
4
6
8
12
16
24h
48h
72h
96h
120h
PE
X
X
X
X
X
!
Full PE may be performed at 
Screening or admission in 
Period 1 only. Further 
full/limited PE at PI’s 
discretion.
!
Limited PE targeted to neuro-
muscular exam to be done 
prior to dosing and post-dose 
on Day 1, 2(±0.5) h and 
~96h post-dosing.
Vital signs (respiratory rate, PR, 
BP)
X
X
X
X
X
X
X
X
X
X
X
X
!
Refer to Section 8.3.2.
12-Lead ECG (triplicate)
X
X
X
X
X
X
X
X
X
X
X
X
!
Singlet at screening.
!
Pre-dose (0h) on Day 1
triplicate measurement to be 
collected at approximately -1h, 
-0.5h and 0h per local 
procedure.
Continuous cardiac telemetry 
monitoring
X ∀∀∀∀∀∀∀X
!
Baseline telemetry to be 
recorded for at least 2 hours 
between admission and prior 
to dosing in Period 1 only 
while awake (Section 8.3.3.1).
Contraception check
X
X
X
X
X
!
Day 5 in last period only if not 
discharged.
Serious and nonserious AE 
monitoring 
X
∀
∀∀∀∀∀∀∀∀∀∀∀
∀
∀
∀
∀
∀
X
X
Study intervention administration
PF-07817883 or Placebo
X
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 30
Table 1.
PART-1: SAD Cohorts
Visit Identifier
Abbreviations used in this table 
may be found in Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Days
29-36
!
Follow-up to occur 28-35 days 
after administration of last
dose of study intervention via 
telephone contact.
Hours After Dose
0 0.25 0.5
1
1.5
2
4
6
8
12
16
24h
48h
72h
96h
120h
Blood Samples for:
Pregnancy test (WOCBP only)
X
X
X
X
!
Day 5 in last period only if not 
discharged.
Safety laboratory (≥4h fasting)
X
X
X
X
X
X
!
Day -1 performed in Periods 2 
and 3 only if discharged from 
CRU.
HIV, HBsAg, HBcAb and 
HCVAb 
X
Serum FSH (post-menopausal 
females only) 
X
Retained Research Samples for 
Genetics (Prep D1) 
X
!
Only in Period 1. 
!
If not collected on the 
designated collection day, 
collect at the next available 
time point.
Plasma PK (PF-07817883) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Drug-related material 
measurement and metabolic 
profiling
X
X
X
X
X
!
Only for selected dose levels. 
The dose level to be decided 
based on emerging data.
Urine Samples for:
Drug screen testing
X
X
!
Not required in Period 2 or 
Period 3 if the participants 
were not discharged.
Urinalysis
X
X
X
X
X
X
Drug-related material 
measurement and metabolic 
profiling
X
X ∀∀∀∀∀∀∀∀∀∀
X
X
X
X
X
!
Only for selected dose levels. 
The dose level to be decided 
based on emerging data.
!
Collected in 24 h intervals.
!
Pre-dose ‘blank’ to be 
collected (Section 8.5.5).
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 31
Table 1.
PART-1: SAD Cohorts
Visit Identifier
Abbreviations used in this table 
may be found in Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Days
29-36
!
Follow-up to occur 28-35 days 
after administration of last
dose of study intervention via 
telephone contact.
Hours After Dose
0 0.25 0.5
1
1.5
2
4
6
8
12
16
24h
48h
72h
96h
120h
Feces Collection for:
Drug-related material 
measurement and metabolic 
profiling
X
X ∀∀∀∀∀∀∀∀∀∀
X
X
X
X
X
!
Only for selected dose levels. 
The dose level to be decided 
based on emerging data.
!
Collected in 24 h intervals.
!
Pre-dose ‘blank’ to be 
collected (Section 8.5.5).
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 32
1.3.2. PART-2: MAD
Table 2.
PART-2: MAD Cohorts (Including Optional Japanese and Chinese Cohorts)
Visit Identifier
Abbreviations used in this table may 
be found in Appendix 10.
Screening
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1 Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day 
9
Day 
10
Day 
11
Day 
12
Days
38-45
!
Days 1, 5, and 10: Refer 
to Table 3.
Informed consent
X
Inclusion/exclusion criteria
X
X
Demographics (including height & 
weight)
X
!
Refer to Section 8.1.1.2. 
Medical/Medicine history
X
X
SARS-CoV-2 RT-PCR
X
!
As per local CRU 
procedures.
COVID-19 signs and symptoms
X
X
!
As per local CRU 
procedures.
CRU Confinement
X
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
X
PE
X
X
X
X
X
!
Full PE may be 
performed at Screening 
or admission. Further 
full/limited PE at PI’s 
discretion.
!
Limited PE targeted to  
neuro-muscular exam to 
be done on Day 5, 
2(±0.5) h and Day 12.
Vital signs (respiratory rate, PR, BP) 
X
X
X
X
X
X
X
X
!
Pre-dose on the dosing 
days.
!
Refer to Section 8.3.2.
12-Lead ECG (triplicate)
X
X
X
X
X
X
X
X
!
Singlet at screening.
!
Pre-dose on the dosing 
days.
!
Pre-dose on Day 1, 
triplicate measurement 
at baseline to be 
collected at 
approximately -1h, -0.5h 
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 33
Table 2.
PART-2: MAD Cohorts (Including Optional Japanese and Chinese Cohorts)
Visit Identifier
Abbreviations used in this table may 
be found in Appendix 10.
Screening
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1 Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day 
9
Day 
10
Day 
11
Day 
12
Days
38-45
!
Days 1, 5, and 10: Refer 
to Table 3.
and 0h per local 
procedure.
Contraception check
X
X
X
X
X
Serious and nonserious AE 
monitoring
X
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
X
X
Study intervention administration
PF-07817883 or Placebo (BID)
X
X
X
X
X
X
X
X
X
X
!
On Day 10, morning 
dose only.
Blood samples for:
Pregnancy test (WOCBP only)
X
X
X
X
Safety laboratory (≥4h fasting)
X
X
X
X
X
X
X
X
HIV, HBsAg, HBcAb and HCVAb 
X
Serum FSH (post-menopausal females 
only)
X
Retained Research Samples for 
Genetics (Prep D1) 
X
!
If not collected on the 
designated collection 
day, collect at the next 
available time point.
Plasma PK (PF-07817883)
X
X
X
X
X
X
X
X
X
X
PK Biomarkers 
X
X
X
Optional PK microsampling (Tasso®)
for PF-07817883
X
X
X
!
NH CRU only.
!
Pre-dose only on Days 6 
and 8.
Optional Blood/plasma ratio sample
X
X
X
!
NH CRU only.
!
Pre-dose only on Days 6 
and 8.
Urine samples for:
Drug screen testing
X
X
Urinalysis
X
X
X
X
X
X
X
X
PK
X
X
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 34
Table 3.
PART-2: PK Days (Day 1, Day 5, Day 10) in MAD Cohorts (Including Optional Japanese and Chinese Cohorts)
Visit Identifier
Abbreviations used in this table may 
be found in Appendix 10.
Treatment Period on PK Days
Notes
Days Relative to Day 1
Day 1
Day 5
Day 10
Planned Hours Post 1st Dose on that 
day
0 0.5 1 1.5 2
4
6
8 12 16 0 0.5 1 1.5 2
4
6
8 12 16 0 0.5 1 1.5 2
4
6
8 12 16
PE
X
!
Limited PE targeted to  
neuro-muscular exam 
to be done at post-dose 
on Day 5, 2(±0.5) h. 
Vital signs (respiratory rate, PR, BP)
X
X
X
X
X
X
X
!
Refer to Section 8.3.2.
12-Lead ECG (Triplicate)
X
X
X
X
X
X
X
!
Pre-dose on Day 1, 
triplicate measurement 
at baseline to be 
collected at 
approximately -1h,
-0.5h and 0h per local 
procedure.
Study intervention administration
PF-07817883 or Placebo (BID dosing) X
X
X
X
X
Blood samples for:
Safety laboratory (≥4h fasting)
X
X
Retained Research Samples for 
Genetics (Prep D1) 
X
PK Biomarker
X
X
X
X
X
Plasma PK (PF-07817883) 
X X X X X X X X X
X X X X X X X X X
X X X X X X X X X X
Optional PK microsampling (Tasso®) 
for PF-07817883
X
Blood/plasma ratio sample
X
Urine samples for:
Urinalysis
X
X
PK and metabolic profiling (BID 
dosing)
X
X ∀∀∀∀∀∀∀X
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 35
1.3.3. PART-3: RBA/FE 
Table 4.
PART-3: RBA/FE Cohort 
Visit Identifier
Abbreviations used in 
this table may be found 
in Appendix 10.
Screening
Periods 1-4
F/U
Contact
E/T
Notes
Days Relative to Day 1
in each period
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Days
29-36
!
Day 3 only in last period if not discharged.
!
F/U only in last period.
Planned Hours Post-
Dose
0
0.5
1
1.5
2
4
6
8
12
16
24h 48h
Informed consent
X
Inclusion/exclusion 
criteria
X
X
!
Period 1 only.
Demographics 
(including height & 
weight)
X
!
Refer to Section 8.1.1.2.
Medical/Medicine 
history
X
X
!
Only if discharged from the site in Periods 2-4.
SARS-CoV-2 RT-PCR
X
!
Not required in Periods 2-4 if the participants 
were not discharged.
!
As per local CRU procedures.
COVID-19 signs and 
symptoms
X
X
!
Not required in Periods 2-4 if the participants 
were not discharged.
!
As per local CRU procedures.
CRU Confinement
X
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
X
PE
X
X
X
!
PE may be performed at Screening or 
admission.
Vital signs (respiratory 
rate, PR, BP)
X
X
X
X
!
Refer to Section 8.3.2.
12-Lead ECG (single)
X
X
X
X
!
Day 3 only in last period.
Contraception check
X
X
X
X
X
!
Day -1 not required in Periods 2 - 4 if the 
participants were not discharged.
!
Day 3 performed only at discharge from the 
CRU.
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 36
Table 4.
PART-3: RBA/FE Cohort 
Visit Identifier
Abbreviations used in 
this table may be found 
in Appendix 10.
Screening
Periods 1-4
F/U
Contact
E/T
Notes
Days Relative to Day 1
in each period
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Days
29-36
!
Day 3 only in last period if not discharged.
!
F/U only in last period.
Planned Hours Post-
Dose
0
0.5
1
1.5
2
4
6
8
12
16
24h 48h
Serious and nonserious 
AE monitoring 
X
∀∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
X
X
Study intervention administration
PF-07817883
X
Blood Samples for:
Pregnancy test 
(WOCBP only)
X
X
X
X
!
Day -1 not required in Periods 2 - 4 if the 
participants were not discharged.
!
Day 3 performed only at discharge from the 
CRU.
Safety laboratory 
(≥4h fasting)
X
X
X
X
!
Day 3 in last Period only
HIV, HBsAg, HBcAb 
and HCVAb 
X
Serum FSH (post-
menopausal females 
only) 
X
Retained Research 
Samples for Genetics
(Prep D1) 
X
!
Period 1 only.
!
If not collected on the designated collection 
day, collect at the next available time point.
Plasma PK
(PF-07817883)
X
X
X
X X
X
X
X
X
X
X
X
X
Urine samples for:
Drug screen testing
X
X
!
Not required in Period 2 or Period 3 or Period 4
if the participants were not discharged.
Urinalysis
X
X
X
X
!
Day 3 in last Period only
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 37
Table 4.
PART-3: RBA/FE Cohort 
Visit Identifier
Abbreviations used in 
this table may be found 
in Appendix 10.
Screening
Periods 1-4
F/U
Contact
E/T
Notes
Days Relative to Day 1
in each period
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Days
29-36
!
Day 3 only in last period if not discharged.
!
F/U only in last period.
Planned Hours Post-
Dose
0
0.5
1
1.5
2
4
6
8
12
16
24h 48h
Other Assessments
Taste Assessment
X
X
X
X
X
!
For suspension, only assessed immediately 
following dosing (within 1 min), 5 min, 10 min 
and 20 minutes of administration.
!
For solid oral formulations, 0h assessment will 
be done within 5 min of administration.
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 38
1.3.4. PART-4: ME 
Table 5.
PART-4: ME Cohort
Visit Identifier
Abbreviations used in this table 
may be found in Appendix 10.
Screening
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5-10
Day 
11
Days
29-36
Planned Hours Post-Dose
0
0.5
1 1.5 2
4
6
8
12 16 24h 48h 72h 96h-
216h
240h
Informed consent
X
Inclusion/exclusion criteria
X
X
Demographics (including height & 
weight)
X
!
Refer to Section 8.1.1.2.
Medical/Medicine history 
X
X
SARS-CoV-2 RT-PCR
X
!
As per local CRU procedures.
COVID-19 signs and symptoms
X
X
!
As per local CRU procedures.
CRU Confinement
X
∀
∀
∀∀∀∀∀∀∀∀
∀
∀
∀
∀
X
!
May be admitted earlier to 
facilitate collection of pre-dose 
fecal sample.
PE
X
X
X
!
PE may be performed at Screening 
or admission.
Vital signs (respiratory rate, PR, 
BP)
X
X
X
X
!
Refer to Section 8.3.2.
12-Lead ECG (Single)
X
X
X
X
Contraception check
X
X
X
X
X
Serious and nonserious AE 
monitoring 
X
∀
∀
∀
∀∀∀∀∀∀∀∀
∀
∀
∀
∀
∀
X
X
Study intervention administration
PF-07817883
X
Blood Samples for:
Safety laboratory (≥4h fasting)
X
X
X
X
HIV, HBsAg, HBcAb and HCVAb 
X
Retained Research Samples for 
Genetics (Prep D1)
X
!
If not collected on the designated 
collection day, collect at the next 
available time point.
Plasma PK (PF-07817883) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 39
Table 5.
PART-4: ME Cohort
Visit Identifier
Abbreviations used in this table 
may be found in Appendix 10.
Screening
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5-10
Day 
11
Days
29-36
Planned Hours Post-Dose
0
0.5
1 1.5 2
4
6
8
12 16 24h 48h 72h 96h-
216h
240h
Drug-related material 
measurement and metabolite 
profiling
X
X
X
X
X
X
X
X
Urine Samples for:
Drug screen testing
X
X
Urinalysis
X
X
X
X
Drug-related material 
measurement and metabolic 
profiling
X
∀
∀∀∀∀∀∀∀∀
X
X
X
X
X
!
Collected in 24 h intervals post-
dose.
!
Pre-dose ‘blank’ to be collected 
(Section 8.5.5).
Feces Collection for:
Drug-related material 
measurement and metabolic 
profiling
X
∀
∀∀∀∀∀∀∀∀
X
X
X
X
X
!
Collected in 24 h intervals post-
dose.
!
Pre-dose ‘blank’ to be collected 
(Section 8.5.5).
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 40
1.3.5. PART-5: DDI 
Table 6.
PART-5: DDI for Sequence 1
Visit Identifier
Abbreviations 
used in this 
table may be 
found in 
Appendix 10.
Screen
ing
Treatment A
Treatment B or Treatment C
F/
U
E
/
T
Notes
Period 1 
Period 2 
Days relative to 
Day 1 in each 
Period
-28 to -2
-1
1
2
1
2
3
4
5
6
7
8
9 10 11 12 38
-
45
!
Days 1, 5, and 10 
in Period 2: Refer 
to Table 8.
Hours After 
Dose
0
0.5
1
1.5
2
4
6
8
12
16
24
36
Informed consent
X
Inclusion/exclusi
on criteria
X
X
Demographics 
(including height 
& weight)
X
!
Refer to 
Section 8.1.1.2.
Medical/Medicin
e history
X
X
SARS-CoV-2 
RT-PCR
X
!
As per local CRU 
procedures.
COVID-19 signs 
and symptoms
X
X
!
As per local CRU
procedures.
CRU 
Confinement
X
∀
∀
∀∀∀
∀
∀∀
∀
∀
∀
∀∀
∀
∀
∀
∀
∀
∀∀∀∀∀X
PE
X
X
X !
PE may be 
performed at 
Screening or 
admission.
Vital signs 
(respiratory rate, 
PR, BP) 
X
X
X
X
X
X
X
X
X
X
X !
Refer to 
Section 8.3.2.
12-Lead ECG 
(Single)
X
X
X
X
X
X
X
X
X
X
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 41
Table 6.
PART-5: DDI for Sequence 1
Visit Identifier
Abbreviations 
used in this 
table may be 
found in 
Appendix 10.
Screen
ing
Treatment A
Treatment B or Treatment C
F/
U
E
/
T
Notes
Period 1 
Period 2 
Days relative to 
Day 1 in each 
Period
-28 to -2
-1
1
2
1
2
3
4
5
6
7
8
9 10 11 12 38
-
45
!
Days 1, 5, and 10 
in Period 2: Refer 
to Table 8.
Hours After 
Dose
0
0.5
1
1.5
2
4
6
8
12
16
24
36
Contraception 
check
X
X
X
X
X
Serious and 
nonserious AE 
monitoring
X
∀
∀
∀
∀∀∀
∀
∀∀
∀
∀
∀
∀∀
∀
∀
∀
∀
∀
∀∀∀∀∀∀X
X
Study intervention administration
PF-07817883
(BID) 
X
X
X
X
X
X
X
X
X
X
!
Only Morning 
dose on Day 10 
in Period 2.
Midazolam
X
X
X
!
Period 2, Day 5 
midazolam dose 
in optional 
Cohort 12 only.
Blood samples for:
Pregnancy test 
(WOCBP only)
X
X
X
Safety laboratory 
(≥4h fasting)
X
X
X
X
X
X
HIV, HBsAg, 
HBcAb and 
HCVAb 
X
Serum FSH 
(post-menopausal 
females only)
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 42
Table 6.
PART-5: DDI for Sequence 1
Visit Identifier
Abbreviations 
used in this 
table may be 
found in 
Appendix 10.
Screen
ing
Treatment A
Treatment B or Treatment C
F/
U
E
/
T
Notes
Period 1 
Period 2 
Days relative to 
Day 1 in each 
Period
-28 to -2
-1
1
2
1
2
3
4
5
6
7
8
9 10 11 12 38
-
45
!
Days 1, 5, and 10 
in Period 2: Refer 
to Table 8.
Hours After 
Dose
0
0.5
1
1.5
2
4
6
8
12
16
24
36
Retained 
Research 
Samples for 
Genetics
(Prep D1) 
X
!
If not collected 
on the designated 
collection day, 
collect at the next 
available time 
point.
Plasma PK
(PF-07817883)
X
X
X
X
X
X
X
X
X
Midazolam
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
!
In Period 2, 
Day 11 at 24 and 
36h and
Day 12 at 48h 
post-dose.
!
Period 2, Day 1
(pre-dose)
sample is 48h 
post-dose sample 
of Period 1.
!
In Period 2, Days
5, 6 and 7 PK 
samples is
optional Cohort 
12 only.
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 43
Table 6.
PART-5: DDI for Sequence 1
Visit Identifier
Abbreviations 
used in this 
table may be 
found in 
Appendix 10.
Screen
ing
Treatment A
Treatment B or Treatment C
F/
U
E
/
T
Notes
Period 1 
Period 2 
Days relative to 
Day 1 in each 
Period
-28 to -2
-1
1
2
1
2
3
4
5
6
7
8
9 10 11 12 38
-
45
!
Days 1, 5, and 10 
in Period 2: Refer 
to Table 8.
Hours After 
Dose
0
0.5
1
1.5
2
4
6
8
12
16
24
36
Urine samples for:
Drug screen 
testing
X
X
Urinalysis
X
X
X
X
X
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 44
Table 7.
PART-5: DDI for Sequence 2 
Visit Identifier
Abbreviations 
used in this 
table may be 
found in
Appendix 10.
Screen
ing
Treatment B or Treatment C
Wash-Out
Treatment A
F/U
E/T
Notes
Period 1
Period 2
Day
-28 
to -2
-1
1
2 
3 
4 
5
6 
7 
8 
9 
10 11 12 13-
17
1
2
3
29-36
!
Day 1, Day 5 and 
Day 10 in 
Period 1: Refer to 
Table 8.
Hours After 
Dose
0
0.5 1 1.5
2
4
6
8
12
16 24 36 48
Informed 
consent
X
Inclusion/exclus
ion criteria
X
X
Demographics 
(including 
height & 
weight)
X
!
Refer to 
Section 8.1.1.2.
Medical/Medici
ne history
X
X
SARS-CoV-2 
RT-PCR
X
!
As per local CRU 
procedures.
COVID-19 
signs and 
symptoms
X
X
!
As per local CRU 
procedures.
CRU 
Confinement
X ∀∀∀∀∀∀∀∀∀
∀∀∀∀∀∀∀∀∀∀∀∀
∀
∀∀∀X
PE
X
X
X
!
PE may be 
performed at 
Screening or 
admission.
Vital signs 
(respiratory rate, 
PR, BP) 
X
X
X
X
X
X
X
X
X
X
X
X
!
Refer to 
Section 8.3.2.
12-Lead ECG 
X
X
X
X
X
X
X
X
X
X
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 45
Table 7.
PART-5: DDI for Sequence 2 
Visit Identifier
Abbreviations 
used in this 
table may be 
found in
Appendix 10.
Screen
ing
Treatment B or Treatment C
Wash-Out
Treatment A
F/U
E/T
Notes
Period 1
Period 2
Day
-28 
to -2
-1
1
2 
3 
4 
5
6 
7 
8 
9 
10 11 12 13-
17
1
2
3
29-36
!
Day 1, Day 5 and 
Day 10 in 
Period 1: Refer to 
Table 8.
Hours After 
Dose
0
0.5 1 1.5
2
4
6
8
12
16 24 36 48
Contraception 
check
X
X
X
X
X
Serious and 
nonserious AE 
monitoring
X
∀∀∀∀∀∀∀∀∀∀
∀∀∀∀∀∀∀∀∀∀∀∀
∀
∀∀∀∀
X
X
Study intervention administration
  PF-07817883
(BID) 
X
X
X
X
X
X
X
X
X
X
!
Only Morning 
dose on Day 10 in 
Period 1.
  Midazolam
X
X
X
!
Period 1, Day 5 
midazolam dose in 
optional Cohort 12
only.
Blood samples for:
  Pregnancy test 
(WOCBP only)
X
X
X
  Safety 
laboratory 
(≥4h fasting)
X
X
X
X
X
X
X
  HIV, HBsAg, 
HBcAb and 
HCVAb 
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 46
Table 7.
PART-5: DDI for Sequence 2 
Visit Identifier
Abbreviations 
used in this 
table may be 
found in
Appendix 10.
Screen
ing
Treatment B or Treatment C
Wash-Out
Treatment A
F/U
E/T
Notes
Period 1
Period 2
Day
-28 
to -2
-1
1
2 
3 
4 
5
6 
7 
8 
9 
10 11 12 13-
17
1
2
3
29-36
!
Day 1, Day 5 and 
Day 10 in 
Period 1: Refer to 
Table 8.
Hours After 
Dose
0
0.5 1 1.5
2
4
6
8
12
16 24 36 48
  Serum FSH 
(post-
menopausal 
females only)
X
  Retained 
Research 
Sample for 
Genetics (Prep 
D1) 
X
  Plasma PK
(PF-07817883)
X
X
X
X
X
X
X
X
X
  Midazolam
X
X
X
X
X
X
X
X X X
X
X
X
X
X
X
X
X
X
!
In Period 1, 
Day 11 at 24 and 
36 h and Day 12 at 
48 h post-dose.
!
In Period 1, Days
5, 6 and 7 PK 
samples in 
optional Cohort 12
only.
Urine samples for:
  Drug screen 
testing
X
X
  Urinalysis
X
X
X
X
X
X
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 47
PART-5 - Treatment B (PF-07817883 with Midazolam): Detailed Sampling Schedule
Table 8.
PART-5: PK Days (Day 1, Day 5, Day 10) in Treatment B 
Visit 
Identifier
Abbreviation
s used in this 
table may be 
found in 
Appendix 10.
Treatment Period on PK Days
Notes
Days Relative 
to Day 1
Day 1
Day 5
Day 10
Planned 
Hours Post 1st
Dose on that 
day
0
0.5 1
1.5 2
4
6
8
12 16
0 0.5 1
1.5 2
4
6
8
12 16
0
0.5 1
1.5 2
4
6
8
12 16
Vital signs 
(respiratory 
rate, PR, BP)
X
X
X
X
X
X
X
!
Refer to 
Section 8.3.2.
12-Lead 
ECG 
X
X
X
X
Study intervention administration
PF-
07817883
(BID dosing) 
X
X
X
X
X
Midazolam
X
X
!
Day 5 AM dosing in 
optional Cohort 12
only.
Blood samples for:
Safety 
laboratory 
(≥4h fasting)
X
X
Retained 
Research 
Sample for 
Genetics
(Prep D1) 
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 48
Table 8.
PART-5: PK Days (Day 1, Day 5, Day 10) in Treatment B 
Visit 
Identifier
Abbreviation
s used in this 
table may be 
found in 
Appendix 10.
Treatment Period on PK Days
Notes
Days Relative 
to Day 1
Day 1
Day 5
Day 10
Planned 
Hours Post 1st
Dose on that 
day
0
0.5 1
1.5 2
4
6
8
12 16
0 0.5 1
1.5 2
4
6
8
12 16
0
0.5 1
1.5 2
4
6
8
12 16
Plasma PK
(PF-0781788
3)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X !
Post-dose samples 
on Day 5 may not 
be collected based 
on emerging PK 
data.
Midazolam
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X !
Day 5 PK samples 
in optional Cohort 
12 only.
Urine samples for:
Urinalysis
X
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 49
1.3.6. PART-6: SE
Table 9.
PART-6: SE
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 6 Days
29-36
!
Follow-up to occur 28-35 
days after administration of 
last dose of study 
intervention via telephone 
contact.
Hours After Dose
0
0.5
1
1.5
2
3
4
6
8
12
24h 48h 72h 96h
120h
Informed consent
X
Inclusion/exclusion criteria
X
X
!
Not required in Period 2 
and Period 3.
Demographics (including height 
& weight)
X
!
Refer to Section 8.1.1.2. 
Medical/Medicine history 
X
X
!
Only required in Periods 2 
and 3 if discharged from the 
site.
SARS-CoV-2 RT-PCR
X
!
Only required in Periods 2 
and 3 if discharged from the 
site.
!
As per local CRU 
procedures.
COVID-19 signs and symptoms
X
X
!
As per local CRU
procedures.
CRU Confinement
X
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 50
Table 9.
PART-6: SE
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 6 Days
29-36
!
Follow-up to occur 28-35 
days after administration of 
last dose of study 
intervention via telephone 
contact.
Hours After Dose
0
0.5
1
1.5
2
3
4
6
8
12
24h 48h 72h 96h
120h
PE
X
X
X
X
X !
Full PE may be performed 
at Screening or admission 
in Period 1 only. Further 
full/limited PE at PI’s 
discretion.
!
Limited PE targeted to 
neuro-muscular exam to be 
done prior to dosing and 
post-dose on Day 1, 2(±0.5)
h and ~120h post-dosing.
Vital signs (respiratory rate, PR, 
BP)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X !
Refer to Section 8.3.2.
12-Lead ECG (triplicate)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X !
Singlet at screening.
!
Pre-dose (0h) on Day 1 
triplicate measurement to be 
collected at approximately -
1h, -0.5h and 0h per local 
procedure.
Continuous cardiac telemetry 
monitoring
X
∀
∀
∀
∀
∀
∀
∀
X
!
Baseline telemetry to be 
recorded for at least 2 hours 
between admission and 
prior to dosing in Period 1 
only while awake
(Section 8.3.3.1).
Contraception check
X
X
X
X
X !
Day -1 in first period only 
and Day 6 in last period 
only if not discharged.
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
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Page 51
Table 9.
PART-6: SE
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 6 Days
29-36
!
Follow-up to occur 28-35 
days after administration of 
last dose of study 
intervention via telephone 
contact.
Hours After Dose
0
0.5
1
1.5
2
3
4
6
8
12
24h 48h 72h 96h
120h
Serious and nonserious AE 
monitoring 
X
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
∀
X
X
Study intervention administration
PF-07817883 or Placebo
X
X
Divided doses (3000 mg) to 
be administered at 0 and 1h
Moxifloxacin or placebo
(open label)
X
X
Moxifloxacin at 0h and 
placebo at 1h post dose
Blood Samples for:
Pregnancy test (WOCBP only)
X
X
X
X !
Day -1 in first period only
and Day 6 in last period 
only if not discharged.
Safety laboratory (≥4h fasting)
X
X
X
X
X
X
X !
Day 6 in last period only.
HIV, HBsAg, HBcAb and 
HCVAb 
X
Serum FSH (post-menopausal 
females only) 
X
Retained Research Samples for 
Genetics (Prep D1) 
X
!
Only in Period 1. 
!
If not collected on the 
designated collection day, 
collect at the next available 
time point.
Plasma Pharmacokinetics 
(PF-07817883) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Plasma Pharmacokinetics 
(Moxifloxacin)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 52
Table 9.
PART-6: SE
Visit Identifier
Abbreviations used in this 
table may be found in 
Appendix 10.
Screening
Periods 1-3
F/U
Contact
E/T
Notes
Days Relative to Day 1
Days
-28 to -2
Day 
-1
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 6 Days
29-36
!
Follow-up to occur 28-35 
days after administration of 
last dose of study 
intervention via telephone 
contact.
Hours After Dose
0
0.5
1
1.5
2
3
4
6
8
12
24h 48h 72h 96h
120h
Urine Samples for:
Drug screen testing
X
X
!
Not required in Period 2 or 
Period 3 if the participants 
were not discharged.
Urinalysis
X
X
X
X
X
X
X
!
Day 6 in last period only.
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
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Page 53
2. INTRODUCTION
PF-07817883 is a potent and selective inhibitor of the SARS-CoV-2 main protease (MPro), 
that is being developed as an oral treatment in patients with COVID-19.
2.1. Study Rationale 
The current study is the FIH study of PF-07817883 in healthy adult participants. It is a 6-part 
study combining PART-1: SAD, PART-2: MAD, PART-3: RBA/FE, PART-4: ME, PART-
5: DDI, and PART-6:SE. PART-1 and PART-2 will evaluate safety, tolerability and PK of 
single and multiple ascending oral doses of PF-07817883 in healthy adult participants, 
respectively. PART-2 of the study may also evaluate the safety, tolerability, and PK in 
Japanese and Chinese participants. PART-3 will evaluate RBA and FE of up to 2 new PF-
07817883 oral formulations. PART-4 will evaluate the ME of PF-07817883 in healthy male 
participants. PART-5 will evaluate the effect of steady-state PF-07817883 on the PK of 
midazolam in healthy participants. PART-6:SE will evaluate safety, tolerability, and PK at 
SE in healthy participants.
Results from this study will inform the study design of the Phase 2/3 studies of PF-07817883 
in COVID-19 patients.
2.2. Background 
Disease Overview
In December 2019, COVID-19 was identified as a new, potentially fatal, respiratory infection 
caused by the novel coronavirus, SARS-CoV-2. The WHO declared COVID-19 a Public 
Health Emergency of International Concern on 20 January 2020 and further characterized the 
disease outbreak as a pandemic on 11 March 2020.1
COVID-19 manifests as a wide range of illnesses, from asymptomatic infection to severe 
pneumonia, ARDS, and death. While the majority of cases (approximately 80%) are 
asymptomatic or mild,2 patients who are hospitalized with COVID-19 may have significant 
morbidity and mortality,3,4 and are at increased risk of developing complications such as 
ARDS, acute cardiac injury, thromboembolic events and/or kidney injury.5,6,7
Current Treatment Options
Although monoclonal antibodies and antivirals have since become available there remains an 
important need to develop therapeutics for the treatment of COVID-19 infection. Several 
mAB became available under EUA, including bebtelovimab, for the treatment of mild to 
moderate COVID-19 infection in select populations. However, other mAB such as 
bamlanivimab with etesivimab and sotrovimab, have since been removed as treatment 
options due to diminished efficacy with the emergence of SARS-CoV-2 variants.8 Antivirals 
such as nirmatrelvir/ritonavir and remdesivir IV are available and considered preferred 
therapy for nonhospitalized adults, while bebtelovimab and molnupiravir are considered 
alternative therapies by the COVID-19 Treatment Guidelines Panel.9 However, these 
therapeutics are limited to outpatient populations with mild to moderate COVID-19 infection 
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PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
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Page 54
at risk for progressing to severe disease. Furthermore, some high-risk patients may be 
ineligible for nirmatrelvir/ritonavir due to DDIs, and remdesivir may be inaccessible for 
some patients as it requires administration in a health care setting and returning for 3 
subsequent days for daily IV dosing. 
Despite these advances, there remains an important need for additional safe and more 
effective therapeutic interventions that do not require administration in a healthcare setting, 
are not limited by DDIs, and with a risk/benefit profile supportive of administration to a 
broader patient population. The direct reduction of viral replication, through inhibition of 
other critical viral enzymes, offers an important mechanism as monotherapy or in 
combination, to achieve greater patient benefit.
Rationale for Development of PF-07817883
The coronavirus main protease (MPro) is a virally encoded enzyme that is critical to the 
SARS-CoV-2 replication cycle, analogous to other obligatory virally encoded proteases 
(eg, HIV Protease, HCV Protease). Mutagenesis experiments with other coronaviruses and 
picornaviruses that are related to SARS-CoV-2 (picornavirus-like supercluster) have 
demonstrated that the activity of the MPro is essential for viral replication. No close human 
analogs of coronavirus MPro enzymes are known, suggesting that appropriate MPro inhibitors 
may function as selective inhibitors of SARS-CoV-2 and other coronaviruses as therapeutic 
agents.
Inhibition of the SARS-CoV-2 MPro by nirmatrelvir/ritonavir has demonstrated the efficacy 
of an antiviral in the reduction in hospitalization and death in mild to moderate COVID-19 
patients with high risk of progression to severe disease. 
2.2.1. Nonclinical Overview
2.2.1.1. Nonclinical Pharmacology
PF-07817883 is a potent (IC50 = 
μM; Ki =
μM) and selective inhibitor of 
SARS-CoV-2 Mpro, exhibiting broad spectrum inhibitory activity against across the 
Coronaviridae family of Mpro enzymes. PF-07817883 binds to the active site of SARS-CoV-2 
Mpro and forms a covalent interaction with Cys145. The key contact residues of Mpro that 
interact with PF-07817883 are highly conserved among alpha and beta coronavirus strains.
PF-07817883 did not inhibit protease activity in a panel of mammalian proteases and was 
inactive against enterovirus 71 and human rhinovirus B, demonstrating its selectivity to the 
coronavirus family.
The in vitro antiviral activity of PF-07817883 against SARS-CoV-2 was demonstrated in 
several cell lines: a differentiated normal African green monkey kidney VeroE6 cells sorted 
for expression of higher levels of the ACE2 receptor, human adenocarcinoma derived 
alveolar basal epithelial cells constitutively expressing the human ACE2 receptor 
(A549-ACE2), and dNHBE cells. In all cellular systems tested, PF-07817883 demonstrates
potent antiviral activity against SARS-CoV-2. In dNHBE cells, a physiologically relevant, 
primary human lung alveolar epithelial cell line, PF-07817883 inhibited SARS-CoV-2 viral 
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CCI
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replication with an EC50 of 0.0343 μM and EC90 of 0.0699 μM after 3 days of drug exposure.
PF-07817883 also exhibited antiviral efficacy against SARS-CoV-1, HCoV-229E, and 
MERS-CoV in cellular systems. In addition, PF-07817883 demonstrated antiviral activities
against Alpha, Beta, Delta, Gamma, Lambda, Mu, and Omicron variants in the Vero
TMPRSS2 and VeroE6 P-gp KO cells.
 
 
 
More details are presented in the IB.
2.2.1.2. Biopharmaceutics and Nonclinical PK
2.2.1.2.1. Biopharmaceutics
PF-07817883 is a neutral compound exhibiting moderate aqueous apparent solubility in 
various bio-relevant media and low passive permeability. In a preliminary passive 
permeability assessment in the RRCK cell line, PF-07817883 exhibited an A-B Papp of 
0.50×10-6 cm/sec, indicating low passive permeability. Preliminary PBPK modeling predicts 
slight improvement (≤20%) in fraction absorbed in fed state compared to fasted state. 
2.2.1.2.2. Nonclinical PK and In Vitro Metabolism
PF-07817883 exhibited moderate CL, with a moderate to low Vss resulting in t1/2 values of 
approximately 10 hours in rats and 2.8 hours in monkeys. Following oral dosing, 
PF-07817883 was rapidly absorbed with moderate bioavailability in rats and monkeys. In the 
rat and monkey repeat dose toxicity studies, mean systemic exposures increased with 
increasing dose and no consistent sex-related differences were observed.
PF-07817883 exhibited low in vitro permeability and preferentially distributed into plasma 
relative to blood cells in all species evaluated. PF-07817883 was relatively unbound in rat
(fu,rat=0.927) and mouse (fu,mouse=0.857) plasma. Concentration-dependent protein binding 
was observed in rabbits and monkeys, while no meaningful concentration-dependent binding 
was observed at ≤10 μM in humans. the
PF-07817883 distributed into the liver and lung to a greater extent than other tissues, while 
distribution into the brain was limited.
 
 
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CYP-mediated oxidation was the primary metabolic route of PF-07817883 in vitro and in 
rats. The primary metabolite across species (M1, PF-07832809) was derived from the 
hydroxylation at the 5-position of the pyrrolidone ring. In vitro studies in human liver 
microsomes indicated metabolism of PF-07817883 was predominantly mediated by CYP3A4
). PF-07817883 was the main drug-related entity in plasma, feces, and urine of rats 
receiving an oral dose of PF-07817883. Most metabolites were observed at trace levels in 
plasma and urine, and M1 was a primary metabolite in feces. The main route of hepatic 
clearance is anticipated to be via oxidative pathways with minor contributions from 
hydrolysis reactions. No unique human metabolites were observed. 
In humans, PF-07817883 is predicted to have a plasma CL of 2.8 mL/min/kg and a Vss of 
1 L/kg with an effective t½ of 4 hours.
In accordance with FDA and EMA DDI guidance,
 
 
 
More details are presented in the IB.
2.2.1.3. Toxicology of PF-07817883
PF-07817883 was assessed in a series of nonclinical studies.
The toxicity of PF-07817883 was evaluated in
GLP toxicity 
studies 
 There were 
no adverse findings in any of the studies. The NOAELs in the
studies 
 over the predicted human unbound Cmax
and AUC24 at a dose of 730 mg BID. 
In general, the nonadverse findings in the nonGLP exploratory studies and the GLP pivotal 
studies were similar.
 
 
 
More details are presented in the IB.
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2.2.2. Clinical Overview
C5091001 is the first clinical study using PF-07817883. As of data snapshot date of 18 
January 2023, the evaluation of PART-1 and the dose escalation cohorts in PART-2 have
completed. PART-4 evaluation is complete, but data were unavailable for inclusion in the 
data snapshot. PART-3 and PART-5 and the optional cohorts of Chinese participants and 
Japanese participants in PART-2: MAD are planned. As of data snapshot date, a total of 34 
healthy adult participants were randomized and treated with PF-07817883 or placebo in 
PART-1 and PART-2. As the study is still ongoing, the summary of safety, tolerability and 
PK data presented here are preliminary and subject to change; however, the overall 
conclusions are not expected to change.
PART-1 included 2 interleaving cohorts with a total of 16 participants with 3-period cross-
over in each cohort. For each period, up to 6 participants received a single oral dose of PF-
07817883 and up to 2 participants received placebo. Single doses of PF-07817883 ranged 
from 150 mg to 4000 mg. Two participants in Cohort 1 were discontinued due to Physician’s 
Decision 
 and Other
 
Two participants in Cohort 2 also discontinued due to Physician’s Decision (
 
 and Withdrawal by Participant (
. 
PART-2 included 3 cohorts evaluating safety, tolerability, and PK data up to 12 days at 200 
mg, 600 mg and 1500 mg doses of PF-07817883 or placebo administered BID for up to 10 
days. As of 18 January 2023, 18 participants were randomized in 3 cohorts in PART-2. One 
participant discontinued in Cohort 4 of PART-2 due to was Other (
.
2.2.2.1. Safety Overview
The preliminary data collected as of the data snapshot (18 January 2023) in PART-1 and 
PART-2 of the Phase 1 study (C5091001) demonstrated an acceptable safety profile at single 
doses of PF-07817883 or placebo ranging from 150 mg to 4000 mg in PART-1, and at doses 
of 200 mg to 1500 mg BID of PF-07817883 or placebo for 10 days in PART-2. Dose 
escalation stopping rules were not triggered and MTD was not achieved. There have been no 
deaths, SAEs or SUSARs reported. 
 
 
Further details on the clinical safety of PF-07817883 are provided in the current IB.
2.2.2.2. Summary of PF-07817883 PK in Human
 
 
 
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Further details on the clinical PK of PF-07817883 are provided in the current IB.
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2.3. Benefit/Risk Assessment
PF-07817883 is not expected to provide any clinical benefit to healthy participants. This 
study is designed primarily to generate safety, tolerability, and PK data for further clinical 
development.
Study C5091001 is the first time that PF-07817883 will be administered to humans. For 
healthy participants participating in this study, no clinical benefit is expected. The purpose of 
the study is to provide the basis for further clinical development of PF-07817883 as a 
potential new, pharmacological agent for the treatment of participants with COVID-19. As of 
14 September 2022, no specific human risks have been identified; postulated risks based on 
nonclinical studies are summarized in Section 2.2.1.3. The clinical impact of these potential 
risks will be minimized through the proposed cautious dose-escalation process wherein 
higher doses of PF-07817883 will be administered only after lower doses have been found to 
be well tolerated with an acceptable safety profile. In addition, this study includes standard, 
intensive, inpatient monitoring of the participants following administration of single, oral 
doses of the study intervention.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of PF-07817883 may be found in the IB, which is the SRSD for this study. The 
SRSD for the midazolam is the EU SmPC or USPI. The SRSD for moxifloxacin is the USPI. 
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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-07817883 
Study Intervention(s): Midazolam 
Cardiac and respiratory effects 
(eg, respiratory depression, 
apnea, respiratory arrest 
and/or cardiac arrest, 
hypotension, changes in the 
HR, vasodilation effects, 
dyspnea, laryngospasm)
Adverse reactions reported following midazolam administration.
A single dose of 5 mg will be 
administered in the study. 
Participants will be monitored by 
vital signs, ECGs and AE collection 
in an inpatient CRU.
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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Hypersensitivity reactions (eg, 
bronchospasm, anaphylactic 
shock, rash, urticaria, pruritus)
Adverse reactions reported following midazolam administration.
A single dose of 5 mg will be 
administered in the study. 
Participants will be monitored by 
vital signs and AE collection in an 
inpatient clinical research unit.
Neurological disturbances (eg, 
drowsiness and prolonged 
sedation, reduced alertness, 
mental confusion, euphoria, 
hallucinations, fatigue, 
headache, dizziness, ataxia, 
postoperative sedation, and 
anterograde amnesia)
Adverse reactions reported following midazolam administration.
A single dose of 5 mg will be 
administered in the study. 
Participants will be monitored by 
vital signs and AEs in an inpatient 
clinical research unit.
Paradoxical reactions (eg, 
agitation, involuntary 
movements (including 
tonic/clonic spasms and 
muscle tremors), 
hyperactivity, hostility, anger 
reactions, aggressiveness, 
paroxysmal excitement, and 
violent actions)
Adverse reactions reported following midazolam administration.
A single dose of 5 mg will be 
administered in the study. 
Participants will be monitored by 
vital signs and AEs collection in an 
inpatient clinical research unit.
Gastrointestinal disturbances 
(eg, nausea, vomiting, 
hiccups, constipation, dry 
mouth)
Adverse reactions reported following midazolam administration.
A single dose of 5 mg will be 
administered in the study. 
Participants will be monitored by 
vital signs and AEs collection in an 
inpatient clinical research unit.
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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): Moxifloxacin
Gastrointestinal disturbances 
(eg, nausea, diarrhoea, 
vomiting)
Adverse reactions reported following moxifloxacin administration
A single dose of 400 mg will be 
administered in the study.  
Participants will be monitored for 
AEs in an inpatient clinical research 
unit. 
Hypersensitivity reactions, 
including anaphylactic 
reactions 
Adverse reactions reported following moxifloxacin administration
A single dose of 400 mg will be 
administered in the study.  
Participants will be monitored by 
vitals and for AEs in an inpatient 
clinical research unit. Participants 
with history of hypersensitivity or 
intolerance to quinolone antibiotics, 
including moxifloxacin, will be 
excluded.  
Peripheral neuropathy, 
exacerbation of myasthenia 
gravis, and central nervous 
system effects including 
agitation, insomnia, dizziness 
and anxiety.   
Adverse reactions reported following moxifloxacin administration
A single dose of 400 mg will be 
administered in the study.  
Participants will be monitored for 
AEs in an inpatient clinical research 
unit. Participants with history of 
myasthenia gravis are excluded. 
Tendinitis and tendon rupture 
Adverse reaction reported following moxifloxacin administration 
A single dose of 400 mg will be 
administered in the study.  
Participants will be monitored for 
AEs in an inpatient clinical research 
unit. 
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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Prolongation of the QT 
interval and isolated cases of 
torsade de pointe
Adverse reaction reported following moxifloxacin administration 
A single dose of 400 mg will be 
administered in the study.  
Participants will be monitored for 
cardiac changes (telemetry and ECG) 
and AEs in an inpatient clinical 
research unit.  Participants with 
known history or risk factors for 
prolonged QT will be excluded. 
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2.3.2. Benefit Assessment
For healthy participants in this study, no clinical benefit is expected. 
2.3.3. Overall Benefit/Risk Conclusion
PF-07817883 is not expected to provide any clinical benefit to healthy participants in this 
study.
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with PF-07817883 are justified by the anticipated benefits that may 
be afforded to participants with COVID-19.
3. OBJECTIVES AND ENDPOINTS
3.1. PART-1: SAD 
Objectives
Endpoints
Primary: 
Primary: 
!
To assess the safety and tolerability following 
single ascending doses of PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
Secondary: 
Secondary: 
!
To assess the plasma PK profile of PF-07817883 
following single ascending doses of 
PF-07817883.
!
Plasma PK parameters of PF-07817883: 
!
Cmax, Tmax, AUClast, Cmax(dn), AUClast(dn).
!
If data permit, AUCinf, AUCinf(dn), t½, Vz/F, 
and CL/F. 
Tertiary/Exploratory: 
Tertiary/Exploratory: 
!
To explore metabolites in plasma, urine, and 
feces, if data permit.
!
Qualitative characterization of metabolites of 
PF-07817883 in pooled plasma, urine, and feces 
if data permit.
!
To determine the extent of excretion of drug-
related material in urine and feces after a single 
oral administration of PF-07817883.
!
Total recovery of drug-related material in urine 
and feces separately, and both routes combined, 
expressed as a percent of total dose 
administered.
!
To evaluate the effect of food (high-fat meal) on 
the exposure of PF-07817883 following a single 
oral dose of PF-07817883, if evaluated 
(Optional).
!
The ratio of AUClast, AUCinf (if data permit) and 
Cmax under fed condition and fasted condition.
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3.2. PART-2: MAD (including optional Japanese and Chinese Cohort) 
Objectives
Endpoints
Primary: 
Primary: 
!
To assess the safety and tolerability following 
multiple ascending doses of PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
Secondary: 
Secondary: 
!
To assess the plasma PK profile of PF-07817883 
on Days 1, 5 and 10 following multiple 
ascending doses of PF-07817883.
!
Plasma PK parameters of PF-07817883: 
!
Cmax, Tmax, AUCtau, C12, Cmax(dn), 
AUCtau(dn), Cav, Rac, Rac,Cmax, PTR,CL/F 
and Vz/F.
!
If data permit, t½.
!
To assess the renal excretion of PF-07817883 on 
Day 10 following multiple ascending doses of 
PF-07817883.
!
PF-07817883 urinary PK parameters: 
!
Aetau and Aetau%, CLr.
Tertiary/Exploratory: 
Tertiary/Exploratory: 
!
To explore PK by microsampling technique(s), 
if evaluated (Optional).
!
Concentration of PF-07817883, if evaluated.
!
To explore RBC partitioning of PF-07817883
(Optional).
!
Ratio of PF-07817883 concentration in plasma 
to that in blood.
!
To explore the effect of PF-07817883 on 
endogenous plasma biomarkers. (Optional)
!
Ratio of plasma concentrations of endogenous 
biomarkers on Day 10 to those before 
PF-07817883 dose.
3.3. PART-3: RBA/FE 
Objectives
Endpoints
Primary: 
Primary: 
!
To determine the oral bioavailability of oral 
formulation(s) of PF-07817883 relative to 
suspension. 
!
The ratio of AUClast, AUCinf and Cmax of oral 
formulation(s) and suspension.
Secondary: 
Secondary: 
!
To evaluate the effect of food (high-fat 
high-calorie meal) on the exposure of 
PF-07817883 following a single oral dose of 
PF-07817883 tablet formulation(s).
!
The ratio of AUClast, AUCinf and Cmax of tablet 
formulation under fed condition and fasted 
condition.
!
To determine the PK of PF-07817883 following 
oral administration of tablet formulation(s) and 
suspension of PF-07817883.
!
Plasma PK parameters of PF-07817883: Tmax,
Cmax, AUClast, if data permit AUCinf, t½, CL/F, 
Vz/F. 
!
To determine the safety and tolerability of 
PF-07817883 following oral administration of 
tablet formulation(s) and suspension of 
PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
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Tertiary/Exploratory: 
Tertiary/Exploratory: 
!
To evaluate the taste attributes of the 
PF-07817883 following oral administration of 
oral formulation(s) and suspension of 
PF-07817883.
!
Taste Assessment Survey Scoring Metrics: 
mouth feel, bitterness, tongue/mouth burn, throat 
burn, overall liking.
3.4. PART-4: ME
Objectives
Endpoints
Primary: 
Primary: 
!
To determine the extent of excretion of drug-
related material in urine and feces after a single 
oral administration of PF-07817883.
!
Total recovery of drug-related material in urine 
and feces separately, and both routes combined, 
expressed as a percent of total dose 
administered.
Secondary: 
Secondary: 
!
To determine the PK of PF-07817883 following 
a single oral administration of PF-07817883.
!
Plasma PK parameters of PF-07817883: Tmax, 
Cmax, AUClast, if data permit AUCinf, t½, CL/F, 
Vz/F. 
!
To determine the safety and tolerability of 
PF-07817883 after a single oral administration 
of PF-07817883.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
Tertiary/Exploratory: 
Tertiary/Exploratory: 
!
To characterize the metabolic profile and 
identify circulating and excreted metabolites 
following administration of a single oral dose of 
PF-07817883, if possible.
!
Metabolic profiling/identification and 
determination of relative abundance of 
PF-07817883 and the metabolites of 
PF-07817883 in plasma, urine, and feces, if 
possible.
3.5. PART-5: DDI
Objectives
Endpoints
Primary Objective: 
Primary Endpoint: 
!
To estimate the effect of PF-07817883 on the PK
of midazolam.
!
Midazolam plasma PK parameters: Cmax and 
AUCinf (if data permit, otherwise AUClast) with 
PF-07817883 (test) versus without 
PF-07817883 (reference).
Secondary Objective: 
Secondary Endpoints: 
!
To evaluate the safety and tolerability of 
PF-07817883 in healthy participants in the 
absence and presence of midazolam.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
!
To evaluate the effects of PF-07817883 on 
additional PK parameters of midazolam in 
healthy participants.
!
Midazolam plasma PK parameters: Tmax, 
AUClast, and if data permit t½, CL/F, and Vz/F 
for midazolam with and without 
coadministration of PF-07817883.
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Objectives
Endpoints
Tertiary/Exploratory Objectives: 
Tertiary/Exploratory Endpoints:
!
To assess the plasma PK profile of PF-07817883 
on Days 1, 5 (optional) and 10 following 
multiple ascending doses of PF-07817883.
!
Plasma PK parameters of PF-07817883: 
!
Cmax, Tmax, AUCtau, C12, Cmax(dn), 
AUCtau(dn), Cav, Rac, Rac,Cmax, PTR,CL/F 
and Vz/F.
!
If data permit, t½.
!
To assess the plasma PK profile of PF-07817883 
on Days 1, 5 (optional) and 10 following 
multiple ascending doses of PF-07817883 in 
Chinese and Japanese participants (Optional).
!
Plasma PK parameters of PF-07817883: 
!
Cmax, Tmax, AUCtau, C12, Cmax(dn), 
AUCtau(dn), Cav, Rac, Rac,Cmax, PTR,CL/F 
and Vz/F.
!
If data permit, t½.
3.6. PART-6: SE 
Objectives
Endpoints
Primary Objective: 
Primary Endpoint: 
!
To assess the safety and tolerability of a SE of 
PF-07817883 administered as split dosing.
!
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs.
Secondary Objective: 
Secondary Endpoints: 
!
To assess the plasma PK of PF-07817883 at an
SE of PF-07817883 administered as split dosing.
!
Plasma PK parameters of PF-07817883: 
!
Cmax, Tmax, AUClast
!
If data permit, AUCinf, t½.
Exploratory Objectives: 
Exploratory Endpoints:
!
To assess the plasma PK of moxifloxacin.
!
Plasma moxifloxacin parameters Cmax, Tmax and 
AUClast.
!
To determine assay sensitivity by comparing the
effect of moxifloxacin 400 mg on QTcF interval
with placebo at historical moxifloxacin Tmax of 3 
hours.
!
Time matched mean differences in QTcF
between moxifloxacin and placebo at the 
historical moxifloxacin Tmax of 3 hours.
!
To determine assay sensitivity by exposure-
response analysis of moxifloxacin
!
Baseline corrected QTcF
!
To determine exposure response analysis of 
PF-07817883
!
Baseline corrected QTcF
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4. STUDY DESIGN
4.1. Overall Design
This study may be conducted at sites in the US and/or EU.
This 6-part, Phase 1, FIH study will combine PART-1: SAD, PART-2: MAD (including 
optional Japanese and Chinese Cohorts), PART-3: RBA/FE, PART-4: ME, PART-5: DDI
and PART-6: SE. Study schema is shown in Section 1.2. PART-1 and PART-2 are a 
randomized, double-blind, sponsor -open, placebo-controlled study to evaluate safety, 
tolerability, and PK of single and multiple escalating oral doses of PF-07817883 in healthy 
adult participants, respectively. PART-2 of the study may also evaluate the safety, 
tolerability, and PK in Japanese and Chinese participants. PART-3 is a randomized, open-
label, cross-over, study to evaluate RBA and FE of 2 new PF-07817883 oral formulations. 
PART-4 is an open-label, non-randomized, single period to evaluate the ME of PF-
07817883. PART-5 is an open-label, randomized, cross-over study to evaluate the effect of 
steady-state PF-07817883 on PK of midazolam in healthy adult participants. PART-6: SE is 
a sponsor-open, randomized, 3-treatment, 3-period, 6-sequence, cross-over, placebo-and 
positive-controlled study to evaluate safety, tolerability, and PK at SE in healthy participants.
PART-1: SAD,dose escalation cohorts (Cohorts 3, 4, 5 and 6) in PART-2: MAD and PART-
6: SE will be conducted at NH CRU only. The optional Japanese and Chinese cohorts in 
PART-2: MAD, PART-3: RBA/FE, PART-4: ME and PART-5: DDI may be conducted at 
NH CRU or BR CRU and will only be initiated after the safety and PK is established in dose 
escalation cohorts at the same or higher dose of PF-07817883. 
In all 6 parts, participants will be screened within 28 days of their first dose of study 
intervention. Participants will be admitted to the CRU on Day -1 or earlier and may be 
discharged at investigator discretion following completion of assessments per the SoA. In
PART-4, participants may be admitted earlier to facilitate collection of pre-dose fecal 
sample. If a participant has any clinically significant, study-related abnormalities at the 
conclusion of a scheduled inpatient portion of the study, the Pfizer medical monitor (or 
designated representative) should be notified and the participant may be asked to remain in 
the CRU until such abnormalities are deemed not clinically significant, or it is safe for 
outpatient follow-up. 
Participants who discontinue for non-safety related reasons prior to completion of the study 
may be replaced, at the discretion of the PI and sponsor. The replacement participant(s) may 
or may not be required to complete all periods of the cohort in which they are participating at 
the discretion of the PI and sponsor.
In PART-1 and PART-2 of the study, the dose levels, frequency of administration and/or 
meal condition may be changed based on emerging PK and safety data. During the SAD and 
MAD the dose increments and planned doses may be adjusted, as the study progresses 
dependent upon emerging PK, safety, and tolerability data. Other intermediate doses or lower 
doses may be administered instead of the planned doses, or changes in dosing frequency or 
titration schemes may be proposed for MAD cohorts if safety/tolerability or PK issues 
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become apparent, if evidence of nonlinear PK dictates the need to escalate more slowly, or if 
subsequent doses are predicted to result in exposures that exceed the target limits. Any 
potential altered dose scheme will be equal to or less than a 3.3-fold increase in exposure 
from the previous highest dose if a higher dose is warranted to achieve exposure. If 
gastrointestinal tolerability issue becomes dose-limiting in PART-1 or PART-2, dosing with 
food (standard meal) or pre-dosing with anti-emetics may be considered. The projected 
average exposure of the altered dose scheme will not exceed the exposure limit specified in
Section 6.6.1. The total daily dose in PART-1 and PART-2 will not exceed 6000 mg. The 
dose escalation will stop if the dose escalation stopping criteria are met as specified in 
Section 6.6.1.
In all cohorts (all parts of the study), participants can be released after completing activities 
specified in the SoA. A telephone follow-up contact will occur between 28 and 35 days after 
the day of last administration of study intervention. At the discretion of the investigator, 
telephone follow-up contact may be substituted with an on-site visit in case of additional 
follow-up of open AEs or clinically significant laboratory findings. 
The total planned duration of participation, from Screening visit to the Follow-up phone call, 
may be up to 10, 10, 9, 8, 11, and 10 weeks for PART-1, PART-2, PART-3, PART-4,
PART-5, and PART-6, respectively.
At the discretion of the sponsor and investigator, participants who were enrolled in PART-1 
or PART-2 may be enrolled in other parts of the study.
4.1.1. PART-1: SAD
SAD will include 2 interleaving cohorts with a total of approximately 16 participants planned 
(approximately 8 participants in each cohort – 6 active: 2 placebo), with 3-period, cross-over 
in each cohort. Period 3 is an optional period which may be used to further explore PK at 
additional doses or assess FE (high-fat high-calorie meal), based on emerging safety, 
tolerability, and PK assessments. For each period, approximately 6 participants will receive a 
single oral dose of PF-07817883, and approximately 2 participants will receive placebo after 
at least 10 hours of fasting. In order to improve gastrointestinal tolerability, if required based 
on emerging safety data, PF-07817883 may also be dosed with standard meal (Section 5.3.2). 
If required to be dosed in fed state, the participants will be required to eat a meal before drug 
administration as specified in Sections 5.3.2 and 6.1. Each participant may receive either a 
single dose of PF-07817883 or a placebo during each period. In each period, participants on 
active treatment in Cohort 1 and Cohort 2 will receive dose levels in dose escalation format 
as specified in provisional dosing scheme shown in Table 11. Except D1 of Cohort 1 in SAD, 
all other dose levels and/or meal condition may be changed based on emerging PK and safety
data. Dose escalation to subsequent dose levels in SAD cohorts will be based on all available 
(a minimum of 48 hours post-dose) safety data and PK over approximately ≥6 hours in a 
minimum of 4 participants (3 active and 1 placebo) at previous dose levels.
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Table 11.
Provisional Dosing Scheme in PART-1: SAD
N
Period 1
Period 2
Period 3a
Cohort 1
N=2
Placebo (PL)
D3
D5
N=2
D1
PL
D5
N=2
D1
D3
D5
N=2
D1
D3
PL
Cohort 2
N=2
PL
D4
TBD
N=2
D2
PL
TBD
N=2
D2
D4
TBD
N=2
D2
D4
TBD
Dose levels are specified in Table 15, Section 4.3.
a.
Period 3 is optional and may be used for evaluation of additional dose levels or FE. Period and dose 
levels for FE may be changed based on emerging PK data. If FE conducted in Period 3, the 
active/Placebo allocation will be the same as equivalent dose used in Periods 1 or 2.
There will be a washout interval of ≥5 days between dosing to a given participant. 
Participants will be required to stay at the CRU for the duration of the washout interval. 
However, they may be released at the discretion of the investigator. The washout interval 
may be adjusted based on data emerging from previous cohorts/periods. 
Optional Period 3 of Cohorts 1 or 2 may be used to explore FE (high-fat high-calorie meal)
or additional doses. If conducted, the active/Placebo allocation will be the same as equivalent 
dose used in Periods 1 or 2.
The urine and feces may be collected for 5 days as specified in the SoA for the measurement 
of total drug-related material and metabolite profiling at the provisional dose levels D3 and
D4. Based on the emerging PK data, the dose level for urine and feces collection may be 
changed. Dietary fiber supplementation and use of laxative (Section 5.3.2.1) should be 
considered with the goal to facilitate at least once daily bowel movement for urine and feces 
collection. The use of the laxative should be recorded.
4.1.2. PART-2: MAD 
The first MAD cohort may start after a total daily dose, which provides comparable or higher 
total daily exposure (24h) in SAD to the projected total daily steady-state exposure (over 
24h) at the starting dose in MAD, is found safe and well tolerated in PART-1 of the study. 
The proposed MAD study design will be parallel cohorts, with 10 days of dosing. PART-2 
will consist of approximately 2 to 6 cohorts including up to 4 optional cohorts (Cohorts 5, 6, 
7 and 8) with approximately 6 participants in each cohort (4 active: 2 placebo). Cohorts 7 and 
8 are optional Japanese and Chinese participants, respectively. In each cohort, approximately 
4 participants will receive 1 of the escalating doses of PF-07817883 as specified in Table 16
(Section 4.3) and approximately 2 participants will receive matching placebo after at least 
10h of fast for the morning dose and 2h of fast for the evening dose. From Day 1-Day 9, PF-
07817883/placebo will be administered every 12h (ie, BID). On Day 10, 
PF-07817883/placebo will be administered at approximately 0h in the morning only with no 
dosing in the evening. If required to be dosed in fed state, the participants will be required to 
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eat a meal before drug administration (as specified in Sections 5.3.2 and 6.1). Dose escalation 
to subsequent dose levels in MAD cohorts will be based on a minimum of 6 days safety data 
and PK over approximately ≥6 hours on Day 5 in a minimum of 4 participants (3 active and 
1 placebo) at previous dose levels. 
Safety, tolerability, and PK may be evaluated in Japanese and Chinese participants as defined 
in Sections 5.1 and 5.2 after multiple oral administration of PF-07817883 in PART-2. If 
conducted, these cohorts will have all evaluations as specified in the SoA for MAD cohorts 
and the dose level in this cohort will be equal or lower than the highest dose level already 
evaluated in healthy Western participants. Frequency of administration and meal condition 
will be based on safety, tolerability, and PK data from MAD cohorts. 
Changes in plasma PK biomarkers such as cholesterol, hydroxycholesterol etc, may be 
explored. If possible, microsampling PK and RBC partitioning, and/or metabolite profiling 
may also be done.
4.1.3. PART-3: RBA/FE
This cohort will be an open-label, randomized, 4-period, 6-sequence cross-over SD cohort 
evaluating the RBA of 2 new PF-07817883 oral formulation(s) compared to PF-07817883
oral suspension and to evaluate the effect of food on the bioavailability of the PF-07817883
oral formulation(s) in healthy adult participants. An exploratory assessment of the taste 
(Appendix 9) may be conducted. Approximately 12 participants will be enrolled in PART-3 
of the study with approximately equal number of participants randomized to 1 of 6 sequences
(Table 12).
Table 12.
Treatment Sequences in PART-3: RBA/FE
Sequence
Period 1
Period 2
Period 3
Period 4
1
A
B
C
D
2
B
C
A
D
3 
C
A
B
D
4 
B
A
C
E
5 
A
C
B
E
6 
C
B
A
E
Treatment A = PF-07817883 600 mg oral suspension SD Fasted; 
Treatment B = PF-07817883 600 mg Formulation 1
Fasted
Treatment C = PF-07817883 600 mg Formulation 2
Fasted
Treatment D = PF-07817883 600 mg Formulation 1
Fed (high-fat meal)
Treatment E = PF-07817883 600 mg Formulation 2
Fed (high-fat meal)
In this part, there will be a washout interval of at least 3 days between dosing to a given 
participant in each period. Participants will be required to stay at the CRU until the discharge 
in the last period. 
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4.1.4. PART-4: ME
This part will include a single cohort of approximately 6 male participants. The dose of this 
cohort will be decided based on the emerging PK and safety data. The selected dose will not 
exceed the highest dose deemed safe in PART-1. Each participant will receive a single dose 
of PF-07817883 at 0 hr on Day 1 along after at least 10 hr of fasting. The plasma for PK and 
metabolic profiling will be collected as specified in the SoA. The urine and feces will be 
collected for 10 days after dosing as specified in SoA to determine excretion routes and 
metabolite profiling. A fecal sample is required prior to dosing on Day 1. Dietary fiber 
supplementation and use of laxative (Section 5.3.2.1) should be considered with the goal to 
facilitate at least once daily bowel movement. The use of the laxative should be recorded. 
The participants will be discharged on Day 11. 
4.1.5. PART-5: DDI
This part may consist of up to 2 cohorts (Cohort 11 and optional Cohort 12). Based on the 
data from the Cohort 11, an optional Cohort 12 may be initiated at a dose lower than the 
600 mg BID. Both cohorts will have 2 treatments, 2 sequences, and 2 periods with a
cross-over design to evaluate the effect of steady-state PF-07817883 on the PK of midazolam 
in healthy adult participants. The dose of PF-07817883 in Cohort 11 is 600 mg BID and dose 
of optional Cohort 12 will be decided based on the emerging PK data from Cohort 11. The 2
sequences are considered to estimate the sequence effect due to differences in the treatment
sequence and the differences in dosing duration. Each enrolled participant will be randomly 
assigned to 1 of 2 sequences to receive 2 treatments in 2 periods. The 2 treatments in this part 
will be: single oral dose of 5 mg midazolam alone (Treatment A) and multiple oral doses of 
PF-07817883 in combination with a single oral dose of 5 mg midazolam (Treatment B). In 
Treatment B, PF-07817883 will be administered every 12h (ie, BID) from Day 1 – Day 9 and
PF-07817883 along with 5 mg midazolam will be administered at approximately 0h in the 
morning on Day 5 (only for optional Cohort 12) and Day 10. For Treatment B, intensive PK 
samples are planned on Day 1, Day 5 and Day 10. If required to be dosed in fed state, the 
participants will be required to eat a meal before drug administration (as specified in 
Sections 5.3.2 and 6.1). A washout of at least 2 and 7 days is required after Treatment A and 
Treatment B, respectively.
A total of approximately 14 healthy participants will be enrolled in each cohort to ensure at 
least 12 participants will complete that cohort. Participants who discontinued from this part
for non-safety reasons may be replaced at the sponsor’s discretion in collaboration with the 
investigator. At the discretion of the sponsor, Japanese and Chinese participants may be 
enrolled in this part to assess PK and safety of PF-07817883 in these ethnic groups. 
Enrolled participants in each cohort will be randomly assigned to 1 of 2 sequences to receive 
2 treatments in 2 periods as in Table 13. Participants will be discharged following completion 
of all assessments as specified in the SoA in Period 2.
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Table 13.
Treatment Sequences in PART-5: DDI
Period 1
Period 2
Sequence 1 (n=7)
Treatment A
Treatment B
or 
Treatment C
Sequence 2 (n=7)
Treatment B
or 
Treatment C
Treatment A
!
Treatment A: Single oral dose of 5 mg midazolam with at least 2-day washout (Treatment A period 
duration: Day 1 to Day 3).
!
Treatment B: PF-07817883 administered orally for 10 days: Day 1 morning to Day 10 morning. On 
Day 10 morning, participants will receive a single oral dose of 5 mg midazolam administered with 
PF-07817883, followed by a 7-day washout (Treatment B period duration: Day 1 to Day 17).
!
Treatment C: PF-07817883 administered orally for 10 days: Day 1 morning to Day 10 morning. On Day 
5 morning and Day 10 morning, participants will receive a single oral dose of 5 mg midazolam 
administered with PF-07817883. A 7-day washout to follow after last PF-07817883 administration
(Treatment C period duration: Day 1 to Day 17).
4.1.6. PART-6: SE
This is a single-dose, randomized, 3-treatment, 3-period, cross-over, 6-sequence, sponsor-
open, placebo-and positive-controlled study to be conducted in approximately 24 adult 
healthy participants. Each participant will be randomly assigned to one of the treatment 
sequences shown in Table 14. The participants randomized to treatment will receive 6000 mg 
as 2 split doses of PF-07817883 3000 mg administered at 0 and 1 h. The participant 
randomized to placebo will receive placebo at 0 and 1h. The participants randomized to 
moxifloxacin will receive moxifloxacin 400 mg and placebo at 0 and 1h, respectively.
Treatment assignments to PF-07817883 and placebo will be blinded to the participants, 
investigator and CRU staff (except pharmacy staff) but open to the sponsor. Administration 
of moxifloxacin and placebo in participants randomized to moxifloxacin treatment will be 
open label. Each period will be separated by at least 7 days of wash-out interval.
Sentinel dosing will be implemented such that 3 participants will be administered with 1 each 
receiving Treatment A, B or C on Day 1 in Period 1. The following day, safety data up to 24
hours post-dose for these participants (including assessment of AEs, vitals, ECGs, and 
telemetry) will be reviewed by the PI prior to dosing the additional 3 participants with 1 each 
on Treatment A, B or C in Period 1. The dosing of the first 6 participants in Period 2 will 
commence upon review of safety data (including assessment of AEs, vitals, ECGs, telemetry, 
and the laboratory assessment at least up to 48h post-dose) from these 6 participants by the 
PI, if any of the stopping criteria as defined in Section 7.4.1 for sentinel dosing is not met. In 
subsequent periods (Period 2 and 3), at the discretion of the investigator, dosing may 
continue as done in Period 1 or all 6 participants may be dosed simultaneously with 2 each 
on Treatment A, B and C in each period.
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Following the review of safety data including assessment of AEs, vitals, ECGs, and 
laboratory assessment (at least up to 48h post-dose in Period 3) of the first 6 participants, the 
dosing of additional participants may be initiated if any of the stopping criteria as defined in 
Section 7.4.2 is not met.
Table 14. Treatment Sequences in PART-6: SE
Sequence
Period 1
Period 2
Period 3
Sequence 1 (n=4)
A
B
C
Sequence 2 (n=4)
B
C
A
Sequence 3 (n=4)
C
A
B
Sequence 4 (n=4)
B
A
C
Sequence 5 (n=4)
A
C
B
Sequence 6 (n=4)
C
B
A
Treatment A: PF-07817883 6000 mg oral suspension administered as 2 split-doses of 3000 mg at 0 and 1h in 
fasted state.
Treatment B: Placebo oral suspension.
Treatment C: Moxifloxacin 400 mg SD at 0h and placebo at 1h in fasted state.
4.2. Scientific Rationale for Study Design
Given the current study is the first to dose PF-07817883 to healthy participants, an escalating 
SD design with careful assessment and ongoing review of safety and PK data of 
PF-07817883 is planned. The 6-part FIH study including SAD, MAD, RBA/FE, ME DDI
and SE design was planned to provide an opportunity to shorten the drug development 
timeline, without compromising the safety of the participants. 
Males and females of 18-60 years of age was selected to better represent the COVID-19 
patient population. PF-07817883 is a non-genotoxic but its effect on embryo-fetal 
development is currently not known. Therefore, both male and female participants are 
required to follow contraception requirements as specified in Section 5.3.1 and Appendix 4. 
 
4.2.1. PART-1: SAD
The cross-over design will permit both a within and between participant assessment of safety, 
tolerability, and PK. Furthermore, 2 interleaving cohorts will permit assessment of safety and 
PK over a wider dose range within a given participant compared to a sequential cohort 
design. To permit an unbiased assessment of safety, the administration of active versus 
placebo in each period will be double blinded to site staff (except those involved in 
preparation of doses) as well as the study participants. 
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For a given participant, dosing will be separated by ≥5 days. This planned dosing interval is 
deemed sufficient to permit washout of previous treatment.
 
At selected doses, the urine and feces may be collected to calculate total excretion of 
drug-related material using 19F-NMR technique and understand metabolic profile as 
described in previous publications.10
4.2.2. PART-2: MAD
The safety and tolerability will be collected up to 12 days to evaluate the impact of 
PF-07817883 on relatively longer dosing; however, the dose escalation decision will be 
based on Day 5 PK. PBPK simulations (including induction and reversible inhibition 
potential) showed that the PK concentration after 5 days of dosing is expected to be very 
close to the steady-state. Therefore, the Day 5 PK and all available safety will be used to 
dose escalate to the next cohort in order to rapidly collect the PK and safety data to initiate 
the study in COVID-19 patients. By Day 10, the PK of PF-07817883 is expected to achieve 
steady-state and therefore, the steady-state plasma and urine PK will be determined on 
Day 10. 
Exploratory dry blood microsampling PK sample and RBC partitioning sample may be 
collected to evaluate the microsampling techniques which may be employed in future clinical 
trials. Exploratory endogenous plasma PK biomarkers such as 
4-#-hydroxycholesterol/cholesterol ratio, CP-1 etc. will be collected to understand the
potential effect of PF-07817883 on metabolic enzyme and/or transporters. 
4.2.3. PART-3: RBA/FE
This part of the study will evaluate bioavailability of up to 2 solid oral dose formulations 
(eg, tablet) relative to the formulation used in PART-1 and/or PART-2 of the study and 
explore the FE on the PK of new formulation(s) in healthy participants. 
 
To aid in the future development of a potential pediatric dosage form of PF-07817883 and 
assess the after taste profile of PF-07817883, PART-3 may assess the taste profile using a 
questionnaire (Appendix 9) at times specified in the SoA.
4.2.4. PART-4: ME 
This part is an open-label, non-randomized, single period cohort to evaluate the ME of PF-
07817883 in healthy male participants. Only males will be included in this study given the 
desire to enroll a homogeneous population due to the small sample size. 
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A single dose of PF-07817883 is considered appropriate as available data do not indicate 
PF-07817883 PK are time-dependent, and hence, single dose data are considered predictive 
of steady-state.
The urine and feces samples collected will only be analyzed to determine the amount of 
drug-related material excreted. Considering the half-life and variability in gastrointestinal 
transit time, feces and urine will be collected up to 10 days after dosing to allow near 
complete collection of the drug or drug-related materials.
4.2.5. PART-5: DDI 
This part is open-label to estimate the effect of steady-state PF-07817883 on the PK of 
midazolam in healthy adult participants. 
 
. Based on half-life of 
CYP3A4 of approximately 29 h,11 a 10 day treatment with PF-07817883 is sufficient to 
allow the concentration of PF-07817883 and CYP3A4 activity level to achieve steady-state. 
Subsequently, a 7-day washout period allows the CYP3A4 activity to return to baseline.
The 2 cohort design will allow up to 2 dose levels of PF-07817883 to be evaluated. A single 
dose midazolam is considered sufficient to estimate the potential induction effect of PF-
07817883. Given 2-7 h half-life of oral midazolam, PK sampling is deemed sufficient to 
characterize PK profile of midazolam.
4.2.6. PART-6: SE
This part is a double-blind, sponsor-open, randomized, 3-period, 6-sequence, cross-over 
cohort to evaluate safety, tolerability, and PK at SE. The highest PF-07817883 dose currently
planned to be evaluated in the Phase 2b study is 600 mg BID.
 
 
 
 
 
 
In SAD, the increase in exposure of PF-07817883 was limited by saturation of absorption at 
3000 mg. In this cohort, PF-07817883 will be administered into split doses at time around 
expected Tmax to achieve higher Cmax of PF-07817883.   
Extensive PK and triplicate ECGs are collected to enable potential exposure-response 
modeling with PF-07817883 concentration and ECG parameters. The cross-over, randomized 
design provides an intrasubject comparison of placebo for exposure-response analysis using 
PF-07817883 concentration and ECG parameters. Considering half-life and inter-individual 
variability in PART-1 of this study, a wash out of ≥7 days was deemed sufficient.
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Sentinel dosing has been implemented as additional safeguards to ensure safety of the 
participants.
In this part of the study, moxifloxacin will be used as the active control for the measurement 
of effect on QT prolongation. An exposure response relationship of moxifloxacin may be 
used for assay sensitivity. Moxifloxacin is a fluoroquinolone antibiotic that produces 
consistent and predictable QT prolongation. Encapsulation of commercially available 
moxifloxacin tablets to achieve blinding has the potential to have an impact on absorption, 
therefore encapsulation will not be employed and moxifloxacin will be administered in an 
unblinded manner. 
The sampling time points have been chosen based on the expected PK profiles of PF-
07817883 and moxifloxacin. The time to reach maximum concentration (Tmax) for PF-
07817883 is approximately
post-dose based on PART-1 and PART-2 of this 
study. This schedule will also allow peak QT effects with moxifloxacin, which have been 
historically observed at 1 to 4 hours post-dose.
4.2.7. Choice of Contraception/Barrier Requirements 
Studies to evaluate the developmental toxicity of PF-07817883 have not been conducted.
Therefore, the use of a highly effective method of contraception is required (see Appendix 4).
4.2.8. Collection of Retained Research Samples
Retained Research Samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
4.3.1. Justification of Dose for PART-1 to PART-5 (Original Protocol, 14 September 
2022)
The approach for dose selection for this study includes consideration of all relevant 
information obtained in non-clinical pharmacology and toxicity studies with PF-07817883. 
Similar to nirmatrelvir, PF-07817883 is expected to exhibit therapeutic anti-SARS-CoV-2 
activity in patients when the free plasma exposure is maintained at or above the in vitro 
EC90 values. The primary HAE cell assay is considered the most relevant for translation and 
has an EC90 value of
nM (≈
ng/mL free concentration
ng/mL total plasma 
concentration, observed geometric mean fu,human =
, which was considered the target 
Ceff.
The human PK of PF-07817883 after single and multiple dose administration was predicted 
using PBPK modeling by scaling in vitro hepatic clearance obtained from HLM in Simcyp®
Version 21 release 1 (Certara, Sheffield, UK). The predicted plasma CL and Vss of 
PF-07817883 are
mL/min/kg and
L/kg, respectively, providing an effective t½ of 
approximately
hours.
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For safety margin calculations (Table 15 and 
Table 16), the unbound fraction was model predicted.
The nonclinical safety profile of PF-07817883 has been adequately characterized in rats and 
non-human primates to support the progression into human clinical studies of up to 14 days 
of dosing. In cynomolgus monkeys and rats, NOAEL was established at 
mg/kg/day. 
Based on the lower systemic exposure, rat was considered the most sensitive species to set 
PK stopping criteria. The daily NOAEL exposure in rat was
μg•h/mL and
μg/mL 
for AUC24,ss and Cmax, respectively. Based on rat NOAEL, after accounting for species 
differences in plasma protein binding [model predicted free fraction at Cav (fu,human,cav)=
, 
assumed free fraction at Cmax (fu,human,cmax)
 fraction unbound in rat (fu,rat)=
, PK 
stopping limit in human is defined as total plasma AUC24 and Cmax of
μg•h/mL and 
μg/mL, respectively.
The planned starting dose of PF-07817883 as a single dose is 150 mg. Being an anti-viral 
agent, the target (MPro) is not expressed in healthy participants hence primary pharmacology-
related effect is not expected in healthy participants. The projected average free
concentration (Caverage,free) of approximately
at 150 mg is more than 
times lower than the observed IC50 (IC50
μM) in off-target pharmacology screening 
panel. The projected total Cmax and the AUC24 of PF-07817883 at the proposed starting dose 
of 150 mg is
μg/mL and
μg•h/mL, which provides approximately
- and
fold 
safety margins (based on free concentrations), respectively. The maximum recommended
starting dose based on HED approach with safety factor of 10 is
mg. Given the absence 
of target from healthy participants, absence of off-target pharmacology and high safety 
margin based on pre-clinical toxicology studies, the proposed starting dose of 150 mg is 
expected to be safe.
Dose escalation is aimed to occur in incremental increases of ≤½ log (ie, up to approximately 
3.3-fold) based on predicted exposures. The margins for the highest proposed single dose 
(6000 mg) established on the free exposures in rats are projected to be approximately
fold 
for Cmax and
fold for AUC24 which are within the NOAEL exposure.
The nominal doses, projected PK exposure parameters and safety margins of PF-07817883
relative to PK stopping limits at the planned doses in SAD are listed in Table 15. Doses 
presented are projected based on nonclinical data and may be modified based on emerging 
safety, tolerability, and PK data. The projected exposures (adjusted based on observed PK) at 
the modified doses will not exceed the PK stopping limits (Section 6.6.1). 
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Table 15.
Predicted Human Exposure and Safety Margins of PF-07817883 Relative 
to Exposure Limits at Planned Dose Levels in SAD
Dose 
Levels
Dose 
(mg)
Cmax 
(μg/mL)
AUC24 
(h*μg/mL)
Predicted 
fu,human at Cmax
c
Predicted 
fu,human at Cav
c
Cmax
a,c
safety 
margin
AUC24
b,c
safety 
margin
D1
D2
D3
D4
D5
D6
a.
Cmax safety margin = free Cmax,ss of PF-07817883 on Day 11 at NOAEL (
mg/kg/day) divided by 
projected free Cmax in humans. 
b.
AUC24 safety margin = free AUC24,ss of PF-07817883 on Day 11 at NOAEL (
mg/kg/day) divided by 
projected free AUC24 in humans. 
c.
Linear regression model predicted fraction unbound in human; Free fraction (fu) in Rat=
 NOAEL 
exposures (Total) =
μg/mL for Cmax and 
μg•h/mL for AUC24.
The starting dose in MAD cohort is planned at
 mg BID; however, the starting dose in 
MAD may be adjusted based on available PK and safety data from the SAD cohorts. Based 
on the current human PK predictions, a dose of approximately 
mg BID would provide 
the Cmin consistently above Ceff in most participants and thus
mg BID is considered 
within the efficacious dose range. Since the target is not expressed in healthy participants and 
lack of evidence of off-target pharmacology (>100 μM), a dose that is expected to be in 
efficacious dose range is proposed as a starting dose in MAD.
Based on the predicted steady-state exposures (Cmax,ss and AUC24,ss),
mg BID is expected 
to provide margins of approximately
-fold for Cmax,ss and
-fold for AUC24,ss relative to 
the free exposure in rats on Day 11 at the NOAEL. All dose levels listed are nominal since 
doses will be driven by exposure. Dose escalation is aimed to occur in incremental increases 
of ≤½ log (ie, up to approximately 3.3-fold) based on predicted exposures.
Due to the uncertainties in the in vitro potencies and PK parameters scaling and anticipated 
interpatient variability, the current intent of the development program is to explore dosing 
regimens resulting in a multiple of this Cmin target. Highest daily dose of PF-07817883 is 
expected to be 6000 mg/day (ie, 3000 mg BID), which is expected to provide margins of 
approximately 
fold for Cmax,ss and 
fold for AUC24,ss relative to the free exposure in rats 
on Day 11 at the NOAEL.
The nominal dosing regimen, projected PK exposure parameters and safety margins of 
PF-07817883 relative to PK stopping limits at the planned doses in MAD are listed in 
Table 16.
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Table 16.
Predicted Human Exposure and Safety Margins of PF-07817883 Relative 
to Exposure Limits at Planned Dose Levels in MAD
Dose 
Regimens
Dose (mg) 
and 
Frequency
Cmax,ss 
(μg/mL)
AUCtau,ss
(h*μg/mL)
Predicted 
fu,human at Cmax
c
Predicted 
fu,human at Cav
c
Cmax
a,c
safety 
margin
AUC24
b,c
safety 
margin
DR1
DR2
DR3
DR4
a.
Cmax,ss safety margin = free Cmax,ss of PF-07817883 on Day 11 at NOAEL (
 mg/kg/day) divided by 
projected free Cmax,ss in humans. 
b.
AUC24,ss safety margin = free AUC24,ss of PF-07817883 on Day 11 at NOAEL (
 mg/kg/day) divided 
by projected free AUC24,ss (ie, 2×AUCtau,ss for BID) in humans.
c.
Linear regression model predicted fraction unbound in human used for free AUC24 and free Cmax
calculation; Free fraction (fu) in Rat=
, NOAEL exposures (Total) =
μg/mL for Cmax,ss and 
μg•h/mL for AUC24,ss. 
All the doses in SAD or MAD cohorts except starting dose of 150 mg in SAD cohort are 
nominal and may be adjusted, as the study progresses depending upon emerging PK, PD, 
safety, and tolerability data. Other intermediate doses or lower doses or repeat doses may be 
administered instead of the planned doses, or changes in dosing frequency or titration 
schemes may be proposed for MAD cohorts if safety/tolerability issues become apparent, if 
evidence of nonlinear PK dictates the need to escalate more slowly, or if subsequent doses 
are predicted to result in exposures that exceed the target limits. However, the projected 
exposure for the modified doses or additional cohorts following either single dose or multiple 
dose administration will not exceed PK stopping limit.
The dosing regimen to be evaluated in optional Chinese and Japanese cohorts will be equal to 
or lower than the safe and tolerated dosing regimen in Western healthy adult participants in 
MAD cohorts. Similarly, the dose of PF-07817883 to be evaluated in PART-3: RBA/FE, 
PART-4: ME and PART-5: DDI will be the dose which will be projected to provide the 
exposure equal to or lower than the exposure already observed in SAD or MAD cohorts at 
safe and tolerated doses.
Given PF-07817883 has a potential of CYP3A induction, midazolam dose of 5 mg was 
selected to ensure sufficient exposure in the presence of most potent inducers.
4.3.2. Justification of Dose for PART-3:RBA/FE
In PART-3:RBA/FE, the dose of PF-07817883 to be evaluated is 600 mg. Based on 
preliminary population PK model using emerging PK data from PART-1 and PART-2, a 
dose of
mg BID is expected to achieve EC90 at Ctrough in more than 90% of the 
participants. Therefore, the highest dose being evaluated in efficacy study is
mg BID.
PF-07817883 was safe and well tolerated up to 
mg in PART-1 when administered as 
suspension in fasted state. The exposure of tablets (Formulation 1 and 2) is expected to be 
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lower than the suspension.
 
. Thus, a dose of PF-07817883 
mg in PART-3 is expected to be safe. 
4.3.3. Justification of Dose for PART-6:SE (Protocol Amendment 2, 31 January 2023)
In PART-6, the total dose planned for PF-07817883 is 6000 mg administered as 2 split doses 
of 3000 mg at 0 and 1h. 
Based on preliminary data from PART-1 and PART-2 of this study, doses of PF-07817883
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
The dose of moxifloxacin to be used in this study is 400 mg. This dose is the typical dose of 
moxifloxacin used as a positive control.
4.4. End of Study Definition
The end of the study is defined as the date of last scheduled procedure shown in the SoA for 
the last participant in the trial, including all parts, globally.
A participant is considered to have completed the study if they have completed all periods of 
the study, including the last scheduled procedure shown in the SoA.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. Use of a 
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prescreening tool is utilized for study recruitment purposes, it will include collection of 
information that reflects the enrollment of a diverse participant population including, where 
permitted under local regulations, age, sex, race, and ethnicity. The following eligibility 
criteria are designed to select participants for whom participation in the study is considered 
appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular participant is suitable for this protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Participants, male or female, 18 to 60 years of age, inclusive, at the time of signing 
the ICD. Only Male participants will be included in PART-4.
!
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
2. Male and female participants who are overtly healthy as determined by medical 
evaluation including medical history, PE, laboratory tests, and standard 12-lead ECG.
Other Inclusion Criteria: 
3. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). A lower entry 
weight of 45 kg may be considered if the total blood volume collection for the study 
does NOT exceed 360 mL over an 8-week period. If the blood volume collected is 
expected to be >360 mL and <550 mL over an 8-week period, then the lower weight 
limit at screening should be 50 kg.
4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
5. For optional Japanese cohort or PART-5 only: Japanese participants who have 
4 Japanese biologic grandparents who were born in Japan.
6. For optional Chinese cohort or PART-5 only: Chinese participants who were born in 
mainland China and both parents are of the Chinese descent.
7. 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.
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5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
!
Any condition possibly affecting drug absorption (eg, gastrectomy, 
cholecystectomy).
!
History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, 
HBsAg, HBcAb, or HCVAb. Hepatitis B vaccination is allowed.
2. 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 COVID-19 pandemic that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for 
the study.
3. Positive test result for SARS-CoV-2 infection at admission. 
4. PART-5 Only: Clinically relevant abnormalities requiring treatment (eg, acute 
myocardial infarction, unstable ischemic conditions, evidence of ventricular 
dysfunction, serious tachy or brady arrhythmias) or indicating serious underlying 
heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure greater than 
NYHA 1, underlying structural heart disease, Wolff Parkinson-White syndrome). 
5. PART-5 Only: History of acute narrow-angle glaucoma, untreated open-angle 
glaucoma, sleep apnea, severe respiratory insufficiency, myasthenia gravis. 
Prior/Concomitant Therapy:
6. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 28 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. (Refer to Section 6.9 for additional details).
7. Current use of any prohibited concomitant medication(s) or participant 
unwilling/unable to use a permitted concomitant medication(s). Refer to Section 6.9.
8. Participants who have received a COVID-19 vaccine within 7 days before screening 
or admission, or who are to be vaccinated with a COVID-19 vaccine at any time 
during the study confinement period.
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Prior/Concurrent Clinical Study Experience:
9. Previous administration with an investigational product (drug or vaccine) within 
30 days (or as determined by the local requirement) or 5 half-lives preceding the first 
dose of study intervention used in this study (whichever is longer).
Diagnostic Assessments:
10. A positive urine drug test.
11. 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.
12. Renal impairment as defined by an eGFR in adults, of <75 mL/min. Based upon 
participant age at screening, eGFR or eCrCl is calculated using the recommended 
formulas in Section 10.7.2 to determine eligibility and to provide a baseline to 
quantify any subsequent kidney safety events. 
13. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, QTcF >450 ms or QRS 
interval >120 ms, 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 the uncorrected QT interval is >450 ms, this interval should be rate-corrected using 
the Fridericia method only and the resulting QTcF should be used for decision 
making and reporting. If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG 
should be repeated twice and the average of the 3 QTcF or QRS values used to 
determine the participant’s eligibility. Computer-interpreted ECGs should be 
overread by a physician experienced in reading ECGs before excluding a participant.
14. 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.
Other Exclusion Criteria:
15. 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 
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5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, 
alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 
1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
16. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing.
17. Unwilling or unable to comply with the criteria in the Section 5.3 of this protocol.
18. Use of tobacco or nicotine containing products in excess of the equivalents of 
5 cigarettes per day or 2 chews of tobacco per day.
19. PART-5 Only: History of sensitivity reactions to midazolam, or any of the 
formulation components. 
20. PART-6 Only: Self-reported history or risk factors for QT prolongation or torsades 
de pointes (eg, organic heart disease, congestive heart failure, hypokalemia, 
hypomagnesaemia, congenital long QT syndrome, myocardial ischemia or 
infarction), congenital deafness, family history of sudden death, and family history of 
long QT syndrome.
21. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members.
22. Pregnant or breastfeeding women.
23. PART-6 Only: Participants who according to the product label for moxifloxacin, 
would be at increased risk if dosed with moxifloxacin (ie, including but not limited to 
participants with history of myasthenia gravis, tendinitis/tendon rupture).
24. PART-6 Only: History of hypersensitivity, allergy, severe adverse drug reaction or 
intolerance to quinolone antibiotics, including moxifloxacin.
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5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Contraception 
The investigator or their designee, in consultation with the participant, will confirm that the 
participant is utilizing an appropriate method of contraception for the individual participant 
and their partner(s) from the permitted list of contraception methods (see Appendix 4,
Section 10.4.4) and will confirm that the participant has been instructed in its consistent and 
correct use. At time points indicated in the SoA, the investigator or designee will inform the 
participant of the need to use acceptable effective contraception consistently and correctly 
and document the conversation and the participant’s affirmation in the participant’s chart. 
Participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception, considering that their risk for pregnancy may have changed since 
the last visit. 
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued and document the requirement to use an 
alternate protocol-specified method, including if the participant will no longer use abstinence 
as the selected contraception method, or if pregnancy is known or suspected in the participant 
or partner.
5.3.2. Meals and Dietary Restrictions
!
Participants must abstain from all food and drink (except water) at least 4 hours prior 
to safety laboratory evaluations and at least 10 hours before morning doses on PK 
days.
!
PART-1, PART-3, PART-4, PART-6 and on PK days in PART-2 and PART-5 (if 
dosed under fasted condition): 
!
Water is permitted until 1 hour prior to study intervention administration at 0h on 
PK days. Water may be consumed without restriction beginning 1 hour after 
dosing at 0h on PK days except PART-6 in which the intake of water remains 
restricted until 1h after 2nd split dosing. Water consumption is not restricted on 
evening dose(s) on PK days and on all doses of non-PK days. 
!
No food will be allowed for approximately 4 hours post-dose (or post-split-doses
in PART-6) in PART-1, PART-3, PART-6 and after the morning dose on PK 
days (Days 1, 5, 10) in PART-2 and PART-5. For all other doses in PART-2 and 
PART-5, no food will be allowed approximately 2 hours before and after dosing. 
!
Noncaffeinated drinks (except grapefruit or grapefruit-related citrus fruit juices (see 
below) may be consumed with meals and the evening snack.
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!
PART-6 Only: Participants will be restricted to consuming ambient temperature or 
warm drinks from Day 1, (prior to baseline ECG measurements), until final ECG 
measurements have been collected in each study period. 
!
Lunch will be provided approximately 4 hours after morning dosing. 
!
Dinner will be provided approximately 9 to 10 hours after morning dosing.
!
An evening snack may be permitted.
!
Participants will refrain from consuming red wine, grapefruit, or grapefruit-related 
citrus fruits (eg, Seville oranges, pomelos, fruit juices) from 7 days prior to the first 
dose of study intervention until collection of the final PK blood sample. 
!
While participants are confined, their total daily nutritional composition should be 
approximately 55% carbohydrate, 30% fat, and 15% protein with the exception of 
dosing days where a high-fat/high-calorie meal will be given prior to study 
intervention. The daily caloric intake per participant should not exceed approximately 
3200 kcal.
If dosed under standard meal condition in PART-1 or PART-3 or PART-4:
Following an overnight fast of at least 10 hours, participants should start a standard breakfast 
approximately 30 minutes prior to the administration of the study intervention. The breakfast 
will be consumed over approximately 20 minutes with study intervention administered 
within approximately 10 minutes after completion of the meal. Participants will be 
encouraged to eat the full standard meal. If participants are unable to complete the entire 
meal, the approximate portion of the meal consumed will be documented. No food will be 
allowed for at least 4 hours post-dose.
!
Water can be allowed as desired except for 1 hour after study intervention
administration. There are no water restrictions prior to dosing for participants dosed 
under fed conditions. 
If dosed under high-fat meal condition in PART-1 or PART-3 or PART-4:
!
Following an overnight fast of at least 10 hours, participants should start a 
high-fat/high-calorie breakfast approximately 30 minutes prior to administration of 
the study intervention. The breakfast will be consumed over approximately 
20 minutes with study intervention administered within approximately 10 minutes 
after completion of the meal. Participants will be encouraged to eat the full meal. If 
participants are unable to complete the entire meal, the approximate portion of the 
meal consumed will be documented. No food will be allowed for at least 4 hours 
post-dose.
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!
The breakfast will be a high-calorie/high-fat test meal. The test meal should derive 
approximately 150, 250 and 500-600 calories from protein, carbohydrate and fat, 
respectively. The following breakfast a representative example of a high-fat, 
high-calorie meal: 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with 
butter, 4 ounces of hash brown potatoes, 8 fluid ounces (240 mL) of whole milk.
!
Water can be allowed as desired except for 1 hour after study intervention
administration. There are no water restrictions prior to dosing for participants dosed 
under fed conditions. 
If dosed under standard meal condition in PART-2 and PART-5:
Morning dosing condition:
Following an overnight fast of at least 10 hours, participants should start a standard breakfast 
approximately 30 minutes prior to the morning administration of the study intervention. The 
breakfast will be consumed over approximately 20 minutes with study intervention
administered within approximately 10 minutes after completion of the meal. Participants will 
be encouraged to eat the full standard breakfast. If participants are unable to complete the 
entire breakfast on PK profile assessment days (Days 1, 5 and 10), the approximate portion 
of the breakfast consumed will be documented. On non-PK days, it is not required to 
document the approximate portion of food consumed. No food will be allowed for at least 
4 hours post-dose on PK days.
Water can be allowed as desired except for 1 hour after study intervention administration on 
PK days. There are no water restrictions on non-PK days neither prior to dosing for 
participants dosed under fed conditions.
Evening dosing condition:
A snack consisting of at least 400 kcal will be provided approximately 20 minutes before 
dosing in the evening. The snacks will be consumed over approximately 10 minutes with 
study intervention administered within approximately 10 minutes after completion of the 
snack. Participants will be encouraged to eat the full snack. There is no food restrictions on 
evening dose(s).
There are no water restrictions on evening dose(s) on PK days and on non-PK days.
5.3.2.1. Dietary Fiber Supplementation (PART-1 and PART-4 only)
To help assure regularity in bowel movements, nutritional composition should include high 
fiber content except when required by the study design (eg, high-fat diet for FE). This may 
include consumption of fiber capsules, at a frequency dictated by investigator, starting with 
the evening meal (ie, approximately 8 or 9 hours post dose) on Day 1, for duration of 
inpatient stay to ensure at least 1 bowel movement per day.
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If an individual participant has not experienced a bowel movement in the first 24 hours after 
dosing water intake should be increased and prune juice should be offered on Day 2.
Despite these measures, if bowel movement does not occur regularly (ie, at least once daily 
bowel movement), consideration should be given to administration of mild laxative/stool 
softener (eg, milk of magnesia or docusate), at investigator’s discretion.
5.3.3. 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 sample of each study 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 sample of each study period. Participants may undergo an alcohol 
breath test or blood alcohol test at the discretion of the investigator.
!
Participants will abstain from the use of tobacco or nicotine containing products for 
24 hours prior to dosing and during confinement in the CRU. 
5.3.4. Activity
!
Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests. Walking at a normal pace will be permitted.
!
In order to standardize the conditions on PK sampling days, participants will be 
required to refrain from lying down (except when required for BP, PR, respiratory 
rate and ECG measurements) for first 4 hours after morning dose, and may be 
required to follow meals and dietary restrictions as specified in Section 5.3.2.
!
PART-1 and PART-6 only: Participants will be confined to the procedure room for 
the first 4 hours after last PF-07817883/placebo or moxifloxacin/placebo (in PART-6 
only) dosing on Day 1 during continuous cardiac monitoring, except to use the 
bathroom. After this, if the equipment setup allows, participants may be ambulatory 
during the ECG monitoring period, but should not engage in strenuous activities. If 
equipment does not allow ambulation, appropriate accommodations will be made by 
the investigator site to facilitate continuous monitoring (eg, bedside urinals should be 
provided to accommodate participants’ excretory needs). 
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. Screen failure data are collected and remain as 
source and are not reported on the CRF.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened at Investigator’s discretion. 
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6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study interventions are all prespecified investigational and non IMPs, medical devices, and 
other interventions (eg, surgical and behavioral) intended to be administered to the study 
participants during the study conduct. 
For the purposes of this protocol, study intervention refers to PF-07817883, placebo, 
moxifloxacin or midazolam.
6.1. Study Intervention(s) Administered
Study Intervention(s)
Intervention Name
PF-07817883
Placebo
Midazolam
Moxifloxacin
Arm Name
(group of 
participants 
receiving a specific 
treatment or no 
treatment)
PART-1 through PART-
5
PART-1 and PART-2
PART-5
PART-6
Type
Drug
Drug
Drug
Drug
Dose Formulation
Suspension/Solution or 
solid oral formulation 
(eg, tablet)
Suspension/Solution or 
solid oral formulation 
(eg, tablet)
Solution
Tablet
Unit Dose 
Strength(s)
Planned oral 
suspension/solution 
doses ranging from 150 
mg to 6000 mg.
Planned nominal solid 
oral formulation
strength 100 - 400 mg 
pending final 
formulation 
development and dose.
0 mg
As available 
locally
As available 
locally.
Dosage Level(s)
Planned oral 
suspension/solution
doses ranging from 
150 mg to 6000 mg.
Planned nominal solid 
oral formulation
strength 100 - 400 mg 
pending final 
formulation 
development and dose.
0 mg
5 mg SD
400 mg
Route of 
Administration
Oral
Oral
Oral
Oral
Use
Experimental
Placebo
Probe substrate
Active control
IMP or 
NIMP/AxMP
IMP
IMP
NIMP/AxMP
NIMP/AxMP
Sourcing
Provided centrally by 
the sponsor.
Provided centrally by 
the sponsor.
Provided locally 
by the CRU.
Provided locally 
by the CRU.
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Study Intervention(s)
Packaging and 
Labeling
Materials (API and
components) for
extemporaneous prep of
oral suspensions will be
provided in bulk.
Tablets will be provided
in bulk. CRU staff will
prepare individual doses
for administration.
Individual dose
containers will be
labeled by site staff per 
country requirement.
Materials (API and
components) for
extemporaneous prep of
oral suspensions will be
provided in bulk.
Solid oral formulation
will be provided in bulk. 
CRU staff will prepare 
individual doses for 
administration.
Individual dose
containers will be
labeled by site staff per 
country requirement.
CRU will procure 
commercially 
labeled materials.
CRU will procure 
commercially 
labeled materials.
Current/Former 
Name(s) or 
Alias(es)
PF-07817883
Placebo
As available
locally
As available
locally.
PF-07817883 and placebo will be provided by Pfizer as bulk powders for extemporaneous 
preparation of oral suspensions at the CRU.
PF-07817883 and placebo will be presented to the participants in individual dosing
containers.
In addition, PF-07817883 and matching placebo may also be supplied as tablets. If provided, 
tablets will be supplied to the CRU in bulk along with individual dosing containers for unit 
dosing.
Midazolam and moxifloxacin will be supplied by the CRU.
6.1.1. Administration
6.1.1.1. PART-1:SAD
If dosed under fasted condition, participants will receive PF-07817883/placebo at 
approximately 08:00 hours (±2 hours) per the SoA following an overnight fast of at least 10h. 
Investigator site personnel will administer with ambient temperature water to a total volume 
of approximately 240 mL. Study intervention will be administered according to the EDR for 
oral suspension. 
If dosed under fed condition (standard meal or high-fat high-calorie meal), the 
PF-07817883/placebo (placebo for PART-1 only) should be administered approximately 
10 minutes after finishing the meal/snack (refer Section 5.3.2 for further details).
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6.1.1.2. PART-2:MAD
If dosed under fasted condition, participants will receive PF-07817883/placebo at 
approximately 08:00 hours (plus or minus 2 hours) per the SoA following an overnight fast 
of at least 10 hours. At least 2h of fast is required for evening dosing. 
Investigator site personnel will administer with ambient temperature water to a total volume 
of approximately 240 mL. Study intervention will be administered according to the EDR for 
oral suspension. 
If dosed under fed condition (meal/snack), the PF-07817883/placebo should be administered 
approximately 10 minutes after finishing the meal/snack (refer Section 5.3.2 for further 
details).
6.1.1.3. PART-3: RBA/FE 
If dosed under fasted condition, participants will receive PF-07817883 at approximately 
08:00 hours (±2 hours) per the SoA following an overnight fast of at least 10h. Participants
will swallow PF-07817883 oral formulation(s) whole (if administered as solid dose units eg,
tablet) and will not chew prior to swallowing. 
Investigator site personnel will administer with ambient temperature water to a total volume 
of approximately 240 mL. Study intervention will be administered according to the EDR for 
oral suspension.
If dosed under fed condition (standard meal or high-fat high-calorie meal), the PF-07817883
should be administered approximately 10 minutes after finishing the meal/snack (refer 
Section 5.3.2 for further details).
6.1.1.4. PART-4: ME
Participants will receive PF-07817883 at approximately 08:00 hours (±2 hours) per the SoA
following an overnight fast of at least 10h. 
Investigator site personnel will administer PF-07817883 oral suspension with ambient 
temperature water to a total volume of approximately 240 mL. PF-07817883 oral suspension 
will be administered according to the EDR for oral suspension.
If dosed under fed condition (meal/snack), the PF-07817883 should be administered 
approximately 10 minutes after finishing the meal/snack (refer Section 5.3.2 for further 
details).
6.1.1.5. PART-5: DDI 
In this part, for Treatment A (midazolam), participants will receive oral solution of 
midazolam at approximately 08:00 hours (±2 hours) per the SoA following an overnight fast 
of at least 10h. For Treatment B, if dosed under fasted condition, participants will receive 
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fast of at least 10 hours. At least 2h of fast is required for evening dosing for BID dosing 
regimen. When dosed together with midazolam, both should be administered within 5 min of 
each other. 
Investigator site personnel will administer with ambient temperature water to a total volume 
of approximately 240 mL. PF-07817883 will be administered according to the EDR for oral 
suspension.
If dosed under fed condition (meal/snack), the PF-07817883 should be administered 
approximately 10 minutes after finishing the meal/snack (refer Section 5.3.2 for further 
details).
6.1.1.6. PART-6: SE 
In this part, following an overnight fast of at least 10 hours, for each period, participants will 
receive split administrations (2 doses) of PF-07817883 or placebo at short intervals (within 
approximately 1 h of the previous dose) or a single dose of moxifloxacin at 0h and placebo at 
1h.
To participants randomized to receive PF-07817883 or placebo the first split-dose of PF-
07817883 or placebo may be administered at 08:00 hours (±2 hours). The second split dose 
will be administered at approximately 1h after the first dose. The participants randomized to 
moxifloxacin would receive moxifloxacin tablet at 08:00 hours and placebo suspension at 1h. 
In all subsequent treatment periods, the timing of dose administration for a given participant
must be matched to that of the first period (±15 minutes). Administration of study 
interventions will be carried out according to the conditions described in the Lifestyle 
Considerations section of this protocol. Investigator site personnel will administer study 
interventions during each period with ambient temperature water to a total volume of 
approximately 240 mL. Participants will swallow the study interventions whole, and will not 
manipulate or chew the study interventions prior to swallowing. 
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm that appropriate conditions 
(eg, temperature) have been maintained during transit for all study interventions
received and any discrepancies are reported and resolved before use of the study 
intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply, prepare, and/or administer study intervention.
3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated recording) area in accordance with the labeled 
storage conditions with access limited to the investigator and authorized site staff. At 
a minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
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indicate the minimum and maximum temperatures since previously documented upon 
return to business.
4. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with actions taken. The site should actively 
pursue options for returning the study intervention to the labeled storage conditions, 
as soon as possible. Once an excursion is identified, the study intervention must be 
quarantined and not used until Pfizer provides permission to use the study 
intervention. Specific details regarding the excursion definition and information to
report for each excursion will be provided to the site in the CRU local procedures.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
6. See the EDR for storage conditions of the study intervention once prepared.
7. Study interventions should be stored in their original containers.
8. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final 
disposition records), such as the IPAL or sponsor-approved equivalent. All study 
interventions will be accounted for using a study intervention accountability 
form/record. 
9. Further guidance and information for the final disposition of unused study 
interventions are provided in the CRU’s local procedures. All destruction must be 
adequately documented. If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff. Dispensing is defined as the provision of study intervention, concomitant treatments, 
and accompanying information by qualified staff member(s) to a healthcare provider, 
participant in accordance with this protocol. Local health authority regulations or investigator 
site guidelines may use alternative terms for these activities.
PF-07817883 and placebo oral dosing suspensions will be prepared in the CRU by 
2 operators, 1 of whom is a pharmacist. Details of dose preparation will be given in a 
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separate EDR. Prepared doses will be provided in unit dose containers and labeled in 
accordance with Pfizer regulations and the investigator site’s labeling requirements.
PF-07817883 and placebo tablets, if used, will be dispensed at the CRU in the individual
dosing containers by 2 operators, 1 of whom is an appropriately qualified and experienced
member of the study staff (eg, physician, nurse, physician’s assistant, nurse practitioner,
pharmacy assistant/technician, or pharmacist). The tablets will be provided in unit dose
containers and labeled in accordance with Pfizer regulations and the clinical site’s labeling
requirements.
Midazolam will be administered to the participant in an unblinded (open-label) fashion.
Midazolam solution will be dispensed at the CRU in the individual dosing containers by
2 operators, 1 of whom is an appropriately qualified and experienced member of the study
staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacy
assistant/technician, or pharmacist). The solution will be provided in unit dose containers and
labeled in accordance with Pfizer regulations and the clinical site’s labeling requirements.
PF-07817883 and placebo will be prepared by qualified unblinded site personnel as per local 
procedure. Blinded study intervention will be administered in a blinded fashion to the 
participant. Blinding procedures do not apply to PART-3, PART-4, and PART-5 of this study 
because it will be conducted as open-label.
Moxifloxacin 400 mg tablets will be prepared in an open-label manner at the NH CRU in the 
individual dosing containers by 2 operators, 1 of whom is an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, 
practitioner, or pharmacist). Prepared doses will be provided in unit dose containers and 
labeled in accordance with Pfizer regulations and the investigator site’s labeling 
requirements.
6.3. Assignment to Study Intervention
The investigator will assign participant numbers to the participants as they are screened for 
the study. Pfizer will provide a randomization schedule to the investigator and, in accordance 
with the randomization numbers, the participant will receive the study treatment regimen 
assigned to the corresponding randomization number.
6.4. Blinding
This is a double-blind, study with optional open-label parts. 
Blinding procedures do not apply to PART-3, PART-4, and PART-5 of this study because it 
will be conducted as open-label. Where the design is open-label, 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.
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6.4.1. Blinding of Participants
Participants will be blinded to their assigned study intervention in PART-1, PART-2 and 
PART-6 (except moxifloxacin) only.
6.4.2. Blinding of Site Personnel
Investigators and other site staff will be blinded to participants’ assigned study intervention
in PART-1, PART-2 and PART-6 (except moxifloxacin) only. 
Participants will be assigned to receive study intervention according to the assigned treatment 
group from the randomization scheme. Investigators will remain blinded to each participant’s 
assigned study intervention throughout the course of the study. 
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately.
CRU Pharmacy staff responsible for preparing all study intervention will be unblinded. CRU 
site staff responsible for providing technical system support to the Pharmacy staff and 
supporting blinded laboratory data processes will be unblinded. These site staff providing 
system support are not involved in any data collection or clinic floor activities.
6.4.3. Blinding of the Sponsor
Limited number of sponsor staff will be unblinded to participants’ assigned study 
intervention in PART-1, PART-2 and PART-6 (except moxifloxacin) of the study for the 
purpose of, including but not limited to, unblinded review, dose escalation, regulatory 
interactions, drug development decisions.
6.4.4. Breaking the Blind 
The method for breaking the blind in this study will be manual. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s
treatment assignment is warranted. Participant safety must always be the first consideration 
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the study medical monitor prior to 
unblinding a participant’s treatment assignment unless this could delay further management
of the participant. If a participant’s treatment assignment is unblinded, the sponsor must be 
notified within 24 hours after breaking the blind. When the blinding code is broken, the 
reason must be fully documented and entered on the CRF.
Blood specimens will be obtained from all participants for PK analysis to maintain the study 
blind at the investigator site. Only the investigator site staff and blinded study monitor, if 
assigned, will be blinded to study treatment. Other Pfizer personnel will be unblinded to 
participant treatments in order to permit real-time interpretation of the safety and PK data; 
and provide information necessary to potentially alter the dose escalation sequence. The 
blinded study monitor, if assigned, will remain blinded to treatment until all monitoring for 
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the study has been completed. Specimens from participants randomized to placebo will not 
be routinely analyzed. To minimize the potential for bias, treatment randomization 
information will be kept confidential by Pfizer unblinded personnel and will not be released 
to the blinded investigator or blinded investigator site personnel until the study database has 
been locked or the investigator requests unblinding for safety reasons.
6.5. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
Study site personnel will examine each participant’s mouth to ensure that the study 
intervention was ingested.
6.6. Dose Modification
Progression to the next dose in PART-1 will occur if the last dose was well tolerated and 
after satisfactory review of the available safety and PK data. Each dose escalation will be 
based on review of the safety data up to a minimum of 48 hours post-dose plus PK 
assessments up to 6 hours post-dose, in at least 3 actively treated participants and at least 
1 placebo-treated participant dosed in the previous dose level. 
Progression to the next dose in PART-2 will occur if the last dose was well tolerated and 
after satisfactory review of the available safety and PK data. Each dose escalation will be 
based on review of the safety data up to a minimum of 6 days plus PK assessments up to 6
hours post-dose on Day 5, in at least 3 actively treated participants and at least 
1 placebo-treated participant dosed in the previous dose level.
Dose for PART-3, PART-4, and PART-5 will be determined based on emerging PK and 
safety data (Section 4.3).
6.6.1. Dose Escalation and Stopping Rules 
Dose escalation stopping rules will be used to determine whether the maximal tolerated dose 
has been attained. Dose escalation may be stopped if it is determined that the limits of safety 
and/or tolerability have been reached. This decision will be made after a discussion takes 
place between the sponsor study team and the investigator. The sponsor study team may not 
overrule the investigator’s decision to stop dose escalation. If dose escalation is stopped 
because of any of these criteria, additional cohorts may receive the same or lower doses of 
the study intervention.
The dose escalation will be terminated based on the following criteria:
!
If 50% or more of the participants receiving active drug at a given dose level (but not 
participants receiving placebo) develop similar clinically significant laboratory, or 
vital sign abnormalities, in the same organ class, indicating dose-limiting intolerance.
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!
If 2 or more of the participants receiving active drug at a given dose level (but not 
participants receiving placebo) develop similar clinically significant ECG 
abnormalities, indicating dose-limiting intolerance.
!
Severe nonserious AEs, considered as, at least, possibly related to study intervention
administration, in 2 participants at a given dose level (but not participants receiving 
placebo), independent of within or not within the same system organ class, indicating 
dose-limiting intolerance.
!
Dosing will be paused if 2 or more participants at a given dose level (but not 
participants receiving placebo) experience a moderate nonserious AE within SMQ of 
peripheral neuropathy or rhabdomyolysis/myopathy, considered as, at least, possibly 
related to study intervention administration. The AEs will be evaluated by the 
sponsor’s unblinded study team. If the events are determined to be dose-limiting, 
doses in subsequent dosing periods may be modified downwards, or dose-escalation 
may be terminated. If it is determined that dosing may resume, a plan that mitigates 
risks to participants with the resumption of dosing will be implemented.
!
Dosing will be paused for any SAE that occurs in a participant receiving active 
treatment until causality is fully assessed by the PI and sponsor. Dosing may resume 
if the SAE is determined to be not drug-related by the PI and sponsor. If the SAE is 
determined to be either drug-related or unknown, either dosing will cease or the SAE 
will be evaluated by the sponsor’s protocol review committee (or similar review 
group), which is independent of the study team and investigators. If the protocol 
review committee determines that dosing may resume, a plan that mitigates risks to 
participants with the resumption of dosing will be implemented. Such a plan could 
include a revision of inclusion/exclusion criteria, repeating or reducing the dose, or 
adding appropriate safety monitoring.
!
It is determined that the limit of safety and/or tolerability has been reached. This 
decision will be made following discussions between the study team and the 
investigator.
!
Other findings that, at the discretion of the study team and investigator, indicate that 
dose escalation should be halted.
!
If, at any dose level, the average exposure reaches or exceeds the PK stopping limits,
total plasma AUC24 (AUC24 = 2 × AUCtau for BID in PART-2) and Cmax of 
μg•h/mL and 
μg/mL.
!
If, based on the observed data, the group mean Cmax or AUC (based on total plasma 
concentration) of the next planned dose is projected to exceed the escalation limits, 
that dose will not be explored. Modified doses may be explored if they are not 
expected to exceed PK stopping criteria.
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Progression to the next dose will occur if the last dose was well tolerated and after 
satisfactory review of the available safety and PK data.
6.7. Continued Access to Study Intervention After the End of the Study
No study intervention will be provided to participants at the end of their study participation.
It is expected that participants will be treated as required with standard-of-care treatments, as 
advised by their usual care physician. 
6.8. Treatment of Overdose
For this study, any dose of PF-07817883 greater than
mg within a 24-hour time period 
(-2 hours) will be considered an overdose.
There is no specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the study medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities as 
medically appropriate and at least until the next scheduled follow-up.
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis within 3 days from the date of the last dose of 
study intervention if requested by the study medical monitor (determined on a 
case-by-case basis).
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the study medical monitor as needed based on the clinical evaluation of the 
participant. 
6.9. Prior and Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 28 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. Limited use of nonprescription medications that are not believed to affect 
participant safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor. Acetaminophen/paracetamol may be used at doses of 
≤1 g/day.
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.
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Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention 
will be documented as concomitant treatments.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: 
!
AE requiring discontinuation in investigator’s view;
!
Pregnancy.
If study intervention is permanently discontinued, the participant will not remain in the study 
for further evaluation. See the SoA for data to be collected at the time of discontinuation of 
study intervention.
7.1.1. ECG Changes
A participant who meets either bulleted criteria based on the average of triplicate ECG 
readings will be withdrawn from the study intervention. 
!
QTcF >500 ms.
!
Change from baseline: QTcF >60 ms and QTcF >450 ms.
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE.
7.1.2. Potential Cases of Acute Kidney Injury
Abnormal values in SCr concurrent with presence or absence of increase in BUN that meet 
the criteria below, in the absence of other causes of kidney injury, are considered potential 
cases of acute kidney injury and should be considered important medical events. 
An increase of ≥0.3 mg/dL (or ≥26.5 μmol/L) in SCr level relative to the participant’s own 
baseline measurement should trigger another assessment of SCr as soon as practically 
feasible, preferably within 48 hours from awareness.
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If the second assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 μmol/L] in SCr
relative to the participant’s own baseline measurement) is ≥0.4 mg/dL (or ≥35.4 μmol/L), the 
participant should be discontinued from the study and adequate, immediate, supportive 
measures taken to correct apparent acute kidney injury.
Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
SCr result. This evaluation should include laboratory tests, detailed history, and physical 
assessment. In addition to repeating SCr, laboratory tests should include serum BUN, serum 
CK, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
examination, and urinary indices. All cases confirmed on repeat testing as meeting the 
laboratory criteria for acute kidney injury, with no other cause(s) of laboratory abnormalities 
identified, should be considered potential cases of drug-induced kidney injury irrespective of 
availability of all the results of the investigations performed to determine etiology of the 
abnormal SCr. If ≥2 healthy participants in a given period in PART-1, PART-3, PART-5,
and PART-6 and in treatment arm in PART-2 and PART-4 are noted to have 2 consecutive
SCr results of ≥0.3 mg/dL (or ≥26.5 μmol/L), an assessment of whether the finding may be 
considered an adverse drug reaction should be undertaken.
7.1.3. COVID-19 
If a participant has COVID-19 during the study, this should be reported as an AE or SAE (as 
appropriate) and appropriate medical intervention provided. Study treatment may continue 
unless the investigator/treating physician is concerned about the safety of the participant, in 
which case temporary or permanent discontinuation may be required. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study include the following:
!
Refused further follow-up;
!
Lost to follow-up;
!
Death;
!
Study terminated by sponsor;
!
Investigator’s decision;
!
Pregnancy.
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At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal.
The participant will be permanently discontinued from the study intervention and the study at 
that time.
If a participant withdraws from the study, they may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1)
for disclosure of future information, no further evaluations will be performed and no 
additional data will be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with them or persons previously authorized by the participant to provide this information. 
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate CRF page. In the event that vital status (whether 
the participant is alive or dead) is being measured, publicly available information should be 
used to determine vital status only as appropriately directed in accordance with local law.
7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
!
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study;
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!
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;
!
Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 
7.4. Stopping Criteria for PART-6:SE
7.4.1. Stopping Criteria for Sentinel Dosing:
!
Dosing will be paused for any SAE considered treatment related or unknown by the 
PI, until causality is fully assessed by the PI and sponsor. Dosing may resume if the 
SAE is determined to be not drug-related by the PI and sponsor.
!
At the discretion of PI, if any participant receiving PF-07817883 or placebo develops
clinically significant laboratory, or vital sign abnormalities, or ECG abnormalities, 
the dosing of additional participants may also be paused until causality is fully 
assessed by the PI and sponsor. Laboratory, vital sign, or ECG abnormalities assessed 
as severe (as defined in assessment of severity in Section 10.3.3) would be considered 
clinically significant, warranting stopping of further dosing . Dosing may resume if 
the event is determined to be not drug-related by the PI and sponsor. 
7.4.2. Stopping Criteria Following Evaluation of Safety Data from the First 6 
Participants (Periods 1 to 3) in PART-6:SE
!
If 50% or more of the participants receiving active drug but not receiving placebo 
develop similar clinically significant laboratory, or vital sign abnormalities, in the 
same organ class, indicating dose-limiting intolerance.
!
If 2 or more of the participants receiving active drug (but not participants receiving 
placebo) develop similar clinically significant ECG abnormalities, indicating dose-
limiting intolerance.
!
Severe nonserious AEs, considered as, at least, possibly related to study intervention 
administration, in 2 participants (but not participants receiving placebo), independent 
of within or not within the same system organ class, indicating dose-limiting 
intolerance.
!
Dosing will be paused if 2 or more participants (but not participants receiving 
placebo) experience a moderate nonserious AE within SMQ of peripheral neuropathy 
or rhabdomyolysis/myopathy, considered as, at least, possibly related to study 
intervention administration. The AEs will be evaluated by the sponsor’s unblinded 
study team. If the events are determined to be dose limiting, doses in subsequent 
dosing periods may be modified downwards, or dose escalation may be terminated. If 
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it is determined that dosing may resume, a plan that mitigates risks to participants 
with the resumption of dosing will be implemented.
!
Dosing will be paused for any SAE that occurs in a participant receiving active 
treatment until causality is fully assessed by the PI and sponsor. Dosing may resume 
if the SAE is determined to be not drug related by the PI and sponsor. If the SAE is 
determined to be either drug related or unknown, either dosing will cease or the SAE 
will be evaluated by the sponsor’s protocol review committee (or similar review 
group), which is independent of the study team and investigators. If the protocol 
review committee determines that dosing may resume, a plan that mitigates risks to 
participants with the resumption of dosing will be implemented. Such a plan could 
include a revision of inclusion/exclusion criteria, repeating or reducing the dose, or 
adding appropriate safety monitoring.
!
It is determined that the limit of safety and/or tolerability has been reached. This 
decision will be made following discussions between the study team and the 
investigator.
!
Other findings that, at the discretion of the study team and investigator, indicate that 
dosing of additional participants should be halted.
8. STUDY ASSESSMENTS AND PROCEDURES
8.1. Administrative and Baseline Procedures
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention
to confirm that they meet the study population criteria for the study. If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.
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 
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obtained prior to the first dose administration meet eligibility criteria for this study. In 
addition, other clinical assessments or specimen collections, eg, retained research samples, 
may be used without repeat collection, as appropriate.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that make it unfeasible to perform the 
test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that they have taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
Safety/laboratory/analyte results that have been collected for the purposes of this study and 
could unblind the study will not be reported to investigative sites or other blinded personnel 
until the study has been unblinded.
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(PR 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 up 
to 390, 235, 210, 160, 360 mL and 485 mL in PART-1, PART-2, PART-3, PART-4, PART-5
and PART-6, respectively. 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 56 consecutive days.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Prior and Concomitant Therapy sections of the protocol.
8.1.1. Baseline Procedures 
8.1.1.1. Medical History
A detailed medical history will be reviewed and recorded at screening and updated on 
admission. This will include detailed medical history as well as a history of prior illegal drug, 
alcohol, and tobacco use as well as blood donation within 60 days prior to enrollment. If the 
participants are discharged between the periods in PART-1:SAD, PART-3:RBA/FE and 
PART-5:DDI, medical history may be updated.
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8.1.1.2. Demographics
Participants’ race, ethnicity, age, gender, height and weight will be recorded at screening . If 
discharged at investigator’s discretion, the demographics will not be recorded in subsequent 
periods. 
8.2. Efficacy Assessments
No efficacy assessment is planned in this study.
8.3. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety
measurements may be obtained at any time during the study to assess any perceived safety 
issues.
8.3.1. Physical Examinations
A complete PE will include, at a minimum, head, ears, eyes, nose, mouth, skin, heart and 
lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological 
systems. 
A brief PE will include, at a minimum, assessments of general appearance, the respiratory 
and cardiovascular systems, and participant-reported symptoms.
PEs may be conducted by a physician, trained physician’s assistant, or nurse practitioner as 
acceptable according to local regulation.
The limited targeted neuromuscular exam as per SoA will include the assessment of the 
motor system (tone and strength), reflexes, coordination and gait.
Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 
surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
PE findings collected during the study will be considered source data and will not be required 
to be reported, unless otherwise noted. Any untoward PE findings that are identified during 
the active collection period and meet the definition of an AE or SAE (Appendix 3) must be 
reported according to the processes in Sections 8.4.1 to 8.4.3.
8.3.2. Vital Signs
8.3.2.1. Blood Pressure and Pulse Rate
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
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(preferably the dominant arm) will be used throughout the study. Participants should be 
instructed not to speak during measurements.
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and PR is acceptable; however, when done 
manually, PR 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 PR should be 
obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and PR will be permitted, 
as necessary, to ensure appropriate collection of safety data.
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 3) must be reported according to the 
processes in Sections 8.4.1 to 8.4.3.
8.3.2.2. Respiratory Rate
Respiratory rate will be measured after approximately 5 minutes of rest in a supine position 
by observing and counting the respirations of the participant for 30 seconds and multiplying
by 2. When BP is to be taken at the same time, respiration measurement will be done during
the 5 minutes of rest and before BP measurement.
8.3.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the HR and measures PR interval, QT interval, QTcF, and QRS 
complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) 
should not be used given the potential risk of discrepancies with ECGs acquired using 
standard limb lead placement. All scheduled ECGs should be performed after the participant
has rested quietly for at least 5 minutes in a supine position. 
For PART-1, PART-2, and PART-6 only:
Triplicate 12-lead ECGs will be obtained approximately 2 to 4 minutes apart; the average of 
the triplicate ECG measurements collected before dose administration on Day 1 in each 
period in PART-1 and PART-6 and on Day 1 in PART-2 will serve as each participant’s 
time-controlled baseline QTcF value.
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) the mean 
value from the triplicate measurements for any post-dose QTcF interval is increased by 
>60 ms from the baseline and is >450 ms; or b) an absolute QT value is ≥500 ms for any 
scheduled ECG. If either of these conditions occurs, then a single ECG measurement must be 
repeated at least hourly until QTcF values from 2 successive ECGs fall below the threshold 
value that triggered the repeat measurement.
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For PART-3, PART-4 and PART-5 only:
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 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG. If either of these conditions occurs, 
then 2 additional ECGs will be collected approximately 2 to 4 minutes apart to confirm the 
original measurement. If the QTcF values from these repeated ECGs remain above the 
threshold value, then a single ECG must be repeated at least hourly until QTc values from 
2 successive ECGs fall below the threshold value that triggered the repeat measurement.
For all parts:
If a) a post-dose QTcF interval remains>≥60 ms from the baseline and is >450 ms; or b) an 
absolute QT value is ≥500 ms for any scheduled ECG for greater than 4 hours (or sooner, at 
the discretion of the investigator); or c) QTcF value get progressively longer, the participant
should undergo continuous ECG monitoring. A cardiologist should be consulted if QTcF
values do not return to less than the criteria listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 8.
8.3.3.1. Continuous Cardiac Monitoring by Telemetry (PART-1 and PART-6 only)
During the time interval shown in the SoA, all abnormal rhythms will be recorded and 
reviewed by the study physician for the presence of rhythms of potential clinical concern. 
The time, duration, and description of the clinically significant event will be recorded in the 
CRF. In addition, a printed record of the tracing(s) of the clinically significant rhythm(s) will 
be made and retained with other source documents.
Telemetry should be collected using a centralized system that also allows for the storage and 
advanced analysis of all recorded data in order to preserve important events for future 
evaluations. Holter monitoring should not be used in parallel with continuous telemetry,
unless it is the only means of data storage available at the investigator site, or verifiable 
arrhythmia quantification is required. To establish a baseline, telemetry should be recorded 
for at least 2 hours between admission and before dosing in Period 1 only while awake. This 
may be done immediately prior to dosing or at some 2-hour continuous interval in the 
24 hours prior to dosing, as long as the recording is performed when the participant is awake. 
Telemetry may be stopped within a reasonably short period of time prior to dosing, in order 
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to avoid interference with study operations conducted immediately before dosing. However, 
it is expected that the telemetry leads will be in place and the system connected prior to 
dosing.
8.3.4. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition.
All laboratory tests with values considered clinically significant and abnormal during 
participation in the study or within 48 hours 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 study medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
DILI.
See Appendix 7 for instructions for laboratory testing to monitor kidney function and 
reporting laboratory test abnormalities.
Participants may undergo random urine drug testing at the discretion of the investigator.
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.3.4.1. Alternative Facilities for Clinical Safety Laboratory Assessment
Not applicable.
8.3.5. COVID-19 Specific Assessments
Participants will undergo COVID-19 related measures as per local CRU procedures.
8.3.6. Pregnancy Testing
A serum pregnancy test is required at screening. Following screening, pregnancy tests may 
be urine or serum tests, and must have a sensitivity of at least 25 mIU/mL. Pregnancy tests 
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will be performed in WOCBP at the times listed in the SoA. Following a negative pregnancy 
test result at screening, appropriate contraception must be commenced and a second negative 
pregnancy test result will be required at the baseline visit prior to the participant’s receiving 
the study intervention. Pregnancy tests will also be done whenever 1 menstrual cycle is 
missed during the active treatment period (or when potential pregnancy is otherwise 
suspected) and at the end of the study. Pregnancy tests may also be repeated if requested by 
IRBs/ECs or if required by local regulations. If a urine test cannot be confirmed as negative 
(eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant 
must be excluded if the serum pregnancy result is positive.
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant’s legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.4.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.4.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before undergoing any study-related procedure and/or receiving study 
intervention), through and including a minimum of 28 calendar days after the last 
administration of the study intervention.
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator.
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment.
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For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and they consider 
the event to be reasonably related to the study intervention, the investigator must promptly 
report the SAE to Pfizer using the CT SAE Report Form.
8.4.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.4.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of its being available.
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.4.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4.
8.4.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
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Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.4.3. Follow-Up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is provided in Appendix 3.
8.4.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure, occurs when a person not enrolled in the study as a participant
receives unplanned direct contact with or exposure to the study intervention. Such exposure
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure.
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
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8.4.5.1. Exposure During Pregnancy
An EDP occurs if: 
!
A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.
!
A male participant who is receiving or has discontinued study intervention
inseminates a female partner.
!
A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of environmental exposure. Below are 
examples of environmental EDP: 
!
A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact.
!
A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then inseminates his female 
partner prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
!
If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 7 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 
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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 should be reported 
as an SAE;
!
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.5.2. Exposure During Breastfeeding
An EDB occurs if: 
!
A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.
!
A female nonparticipant is found to be breastfeeding while being exposed or having 
been exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports 
that she is breastfeeding after having been exposed to the study intervention by 
ingestion.  
The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the CT SAE Report Form. When EDB occurs in the setting of environmental exposure, 
the exposure information does not pertain to the participant enrolled in the study, so the 
information is not recorded on a CRF. However, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
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An EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB.
8.4.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the CT SAE Report Form regardless of 
whether there is an associated SAE. Since the information about the occupational exposure 
does not pertain to a participant enrolled in the study, the information is not recorded on a 
CRF; however, a copy of the completed CT SAE Report Form must be maintained in the 
investigator site file.
8.4.6. Cardiovascular and Death Events
Not applicable.
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.4.8. Adverse Events of Special Interest
AESIs are examined as part of routine safety data review procedures throughout the clinical 
trial and as part of signal detection processes. Should an aggregate analysis indicate that 
these prespecified events occur more frequently than expected, eg, based on epidemiological 
data, literature, or other data, then this will be submitted and reported in accordance with 
Pfizer’s safety reporting requirements. Aggregate analyses of safety data will be performed 
on a regular basis per internal SOP. 
All AESIs must be reported as an AE or SAE following the procedures described in 
Section 8.4.1  through 8.4.4. An AESI is to be recorded as an AE or SAE on the CRF. In 
addition, an AESI that is also an SAE must be reported using the CT SAE Report Form.
8.4.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.4.9. Medical Device Deficiencies
Not applicable.
8.4.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
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Medication errors are recorded and reported as follows:
Recorded on the 
Medication Error Page 
of the CRF
Recorded on the 
Adverse Event Page 
of the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
All (regardless of whether 
associated with an AE)
Any AE or SAE associated 
with the medication error
Only if associated with an 
SAE
Medication errors include:
!
Medication errors involving participant exposure to the study intervention;
!
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.5. PK
8.5.1. Plasma for Analysis of PF-07817883 PK, Total Drug-Related Material
Measurement, and Metabolic Profiling
Blood samples of approximately 3 mL, to provide approximately 1 mL of plasma, will be 
collected for measurement of plasma concentrations of PF-07817883 as specified in the SoA. 
In PART-2: MAD portion of the study conducted at NH CRU only, exploratory 
microsampling PK blood samples for the measurement of PF-07817883 concentrations may 
be collected. Total blood volume for exploratory microsampling PK will not exceed 0.1 mL 
at each time point specified in the SoA. When an exploratory microsampling PK blood 
sample is collected, a 0.1 mL portion of the PK blood sample will also be collected and used 
to determine the blood to plasma ratio of PF-07817883. In PART-1 (at selected doses at 
which urine and feces are collected) and PART-4 of the study, blood samples of 
approximately 10 mL may be collected for  the measurement of drug-related materials using 
19F-NMR and/or metabolic profiling as specified in the SoA. Instructions for the collection 
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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.
Samples collected for analyses of PF-07817883 concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study, for metabolite 
identification and/or evaluation of the bioanalytical method, or for the measurement of PK 
biomarkers or for other internal exploratory purposes.
Genetic analyses will not be performed on these plasma samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained.
Samples collected for measurement of plasma concentrations of PF-07817883 will be 
analyzed using a validated analytical method in compliance with applicable SOPs. Samples 
collected for exploratory PK may be analyzed with either validated or qualified methods. 
This exploratory data will not be included in the clinical study report. Potential metabolites 
may be analyzed with either validated or exploratory methods.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Drug concentration information that would unblind the study will not be reported to 
investigator sites or blinded personnel until the respective cohort of study has been 
unblinded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
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8.5.2. Plasma for PK Analysis of Midazolam (PART-5: DDI only)
Blood samples of approximately 4 mL, to provide approximately 1.5 mL plasma, will be 
collected for measurement of plasma concentrations of midazolam as specified in the SoA. 
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor. The actual date and time (24-hour clock time) of each 
sample will be recorded.
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time 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.
Samples will be used to evaluate the PK of midazolam and its metabolites (if necessary). 
Samples may also be used to evaluate safety aspects related to concerns arising during or 
after the study and/or evaluation of the bioanalytical method, or for the measurement of PK 
biomarkers or for other internal exploratory purposes.
Genetic analyses will not be performed on these plasma samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained.
Samples collected for measurement of plasma concentrations of midazolam will be analyzed 
using a validated analytical method in compliance with applicable SOPs. Samples collected 
for exploratory PK may be analyzed with either validated or qualified methods. This 
exploratory data will not be included in the clinical study report. Potential metabolites may 
be analyzed with either validated or exploratory methods.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Drug concentration information that would unblind the study will not be reported to 
investigator sites or blinded personnel until the respective cohort of study has been 
unblinded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
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be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.5.3. Plasma for PK Analysis of Moxifloxacin (PART-6: SE only)
Blood samples of approximately 4 mL, to provide approximately 1.5 mL plasma, will be 
collected for measurement of plasma concentrations of moxifloxacin as specified in the SoA. 
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor. The actual date and time (24-hour clock time) of each 
sample will be recorded.
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after dose administration that are obtained within 10% 
of the nominal time 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.
Samples will be used to explore the PK of moxifloxacin. Samples collected for this 
exploratory PK may be analyzed with either validated or qualified methods. Samples may 
also be used to evaluate safety aspects related to concerns arising during or after the study 
and/or evaluation of the bioanalytical method, or for the measurement of PK biomarkers or 
for other internal exploratory purposes. This exploratory data will not be included in the 
CSR.
Genetic analyses will not be performed on these plasma samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case by case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
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8.5.4. Plasma for the Measurement of PK Biomarkers (PART-2) 
Blood samples of approximately 4 mL, to provide approximately 1.5 mL of plasma, will be 
collected for measurement of plasma concentrations of endogenous PK biomarkers, such as
cholesterol, hydroxycholesterol, CP-I, CP-III, IBC etc, as specified in the SoA. Instructions 
for the collection and handling of biological samples will be provided in the laboratory 
manual or by the sponsor. The actual date and time (24-hour clock time) of each sample will 
be recorded.
Sample collected for PK biomarkers may also be used to evaluate safety or efficacy or PK
aspects related to concerns arising during or after the study, for metabolite identification 
and/or evaluation of the bioanalytical method, or for the measurement of PK biomarkers or 
for other internal exploratory purposes.
8.5.5. Urine PK (PART-2 only)
Urine samples will be collected for an interval as specified in the SoA and mixed thoroughly 
and the total volume will be measured and recorded on the CRF. An aliquot of approximately
5 mL will be collected for the measurement of urine concentrations of PF-07817883. 
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 start 
and end of each collection interval will be recorded.
The urine blank (approximately 5 mL) for PK will be obtained prior to dosing.
Samples collected for measurement of urine concentrations of PF-07817883 will be analyzed 
using a validated analytical method in compliance with applicable SOPs. Potential 
metabolites may be analyzed with either validated or exploratory methods.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case by case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Drug concentration information that would unblind the study will not be reported to 
investigator sites or blinded personnel until the respective cohort of the study has been 
unblinded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
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As part of understanding the PK of the study drug, samples may be used for exploratory 
purposes, metabolite identification and/or evaluation of the bioanalytical method. These data 
will be used for internal exploratory purposes and will not be included in the CSR. 
8.5.6. Urine and Feces for Measurement of Drug-Related Material and Metabolic 
Profiling (PART-1 and PART-4)
Urine will be collected for determination of total drug-related material and metabolite 
profiling as specified in the SoA. The participants will force void before oral dosing. Prior to 
dosing on Day 1 (within 24 hours), each participant must empty his or her urinary bladder; an 
aliquot from this urine will serve as the “urine blank”. The details regarding the collection, 
processing, storage and shipping of the urine samples will be provided in the lab manual and 
supporting documentation. 
Feces will be collected for determination of total drug-related material by 19F-NMR 
spectroscopy and metabolite profiling as specified in the SoA. A pre-dose fecal sample 
within 48 hours prior to dosing should be collected.
Details of the collection of aliquots, volume, processing, storage and shipping of the urine 
and feces samples will be provided in the lab manual and supporting documentation. The 
actual date and time (24-hour clock time) of each sample will be recorded.
At the discretion of the sponsor, one or more assessments on urine and feces may not be 
conducted if deemed unnecessary by the sponsor. 
8.6. Genetics
8.6.1. Specified Genetics
Specified genetic analyses are not evaluated in this study.
8.6.2. Retained Research Samples for Genetics
A 4 mL blood sample optimized for DNA isolation Prep D1 will be collected according to 
the SoA, as local regulations and IRBs/ECs allow.
Retained Research Samples may be used for research related to the study intervention(s). 
Genes and other analytes (eg, proteins, RNA, nondrug metabolites) may be studied using the 
retained samples. 
See Appendix 5 for information regarding genetic research. Details on processes for 
collection and shipment of these samples can be found in the laboratory manual and 
supporting documentation.
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8.7. Biomarkers
8.7.1. Specified Gene Expression (RNA) Research 
Specified gene expression (RNA) research is not included in this study.
8.7.2. Specified Protein Research 
Specified protein research is not included in this study.
8.7.3. Specified Metabolomic Research 
Specified metabolomic research is not included in this study.
8.7.4. Retained Research Samples for Biomarkers
Not applicable.
8.8. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.10. Taste Assessment of PF-07817883 (PART-3 only)
The sensory attributes of PF-07817883 will be evaluated by the participant using a Taste 
Assessment Questionnaire (Appendix 9). When suspension is to be administered, each 
participant will complete the Taste Assessment Survey immediately following dosing 
(within 1 min) plus at 5, 10, and 20 minutes post oral administration of PF-07817883 oral 
suspension. For solid oral formulations, the taste assessment will be completed immediately 
after dosing (within 5 min) and at 1, 2, 4 and 8h post-dose as specified in SoA.
All efforts will be made to initiate the questionnaire at the nominal time relative to dosing; 
however, it will not be captured as a protocol deviation, as long as the exact time of 
assessment is noted on the source document and the CRF.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in the SAP, which will be maintained by the sponsor. 
The SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
There are no statistical hypotheses for this study.
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9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set 
Description 
Enrolled 
"Enrolled" means a participant's, agreement to 
participate in a clinical study following 
completion of the informed consent process and 
assignment to study intervention. A participant 
will be considered enrolled if the informed 
consent is not withdrawn prior to participating 
in any study activity. Potential participants who 
are screened for the purpose of determining 
eligibility for the study, but do not participate in 
the study, are not considered enrolled, unless 
otherwise specified by the protocol.
Evaluable
All participants randomly assigned to study 
intervention and who take at least 1 dose of 
study intervention for the given part of the 
study.
Safety
All participants randomly assigned to study 
intervention and who take at least 1 dose of 
study intervention. Participants will be analyzed 
according to the product they actually received.
PK Concentration Set
All participants randomly assigned to study
intervention and who take at least 1 dose of 
study intervention and in whom at least 
1 concentration value is reported for the given 
part of the study.
PK Parameter Set
All participants randomly assigned to study
intervention and who take at least 1 dose of 
study intervention and in whom at least 1 of the 
PK parameters of interest are reported for the 
given part of the study.
9.3. 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.
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9.3.1. General Considerations
The data from each part of the study will be analyzed and reported separately in a single CSR 
issued at the end of this study.
9.3.2. Primary Endpoint(s) Analysis
The primary endpoints in PART-1, PART-2 and PART-6 are related to safety/tolerability 
with analyses as described in Section 9.3.5.
The primary endpoints in PART-3 and PART-5 are the plasma PK endpoints whose analyses 
are described in Sections 9.3.3.1 and 9.3.3.2.
The primary endpoints in PART-4 are percent recovery and cumulative recovery of 
drug-related material in urine and feces determined based on total administered dose. Percent 
recovery of drug-related material in urine and feces will be determined based on total 
administered dose. The total recovery of drug-related material in urine and feces and their 
combination will be listed and summarized. 
9.3.3. Secondary Endpoint(s) Analysis
The secondary endpoints in PART-1, PART-2, PART-4 and PART-6 as well as the primary 
endpoints in PART-3 and PART-5 related to PK are described herein. 
9.3.3.1. PK Analysis 
9.3.3.1.1. Derivation of PK Parameters 
Plasma PK parameters for PF-07817883 will be derived (if data permit) from the 
concentration-time data using standard noncompartmental methods following a single oral 
dose (Table 17) and multiple oral doses (Table 18). Urine PF-07817883 PK parameters are 
described in Table 18. Actual PK sampling times will be used in the derivation of PK 
parameters. In the case that actual PK sampling times are not available, nominal PK sampling 
time will be used in the derivation of PK parameters.
Table 17.
Plasma PF-07817883 PK Parameters for PART-1: SAD, PART-3: 
RBA/FE, PART-4: ME and PART-6: SE, Midazolam PK Parameters in 
PART-5: DDI, and Moxifloxacin PK Parameters in PART-6: SE
Parameter
Part of the 
Study
Definition
Method of Determination
AUClasta,c
1, 3, 4, 5, 6
Area under the plasma concentration-
time curve from time 0 to the time of 
the last quantifiable concentration (Clast)
Linear/Log trapezoidal method
AUCinfb
1, 3, 4, 5, 6
Area under the plasma concentration-
time curve from time 0 extrapolated to 
infinite time
AUClast + (Clast*/kel),
where Clast* is the predicted 
plasma concentration at the last 
quantifiable time point from the 
log-linear regression analysis
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Table 17.
Plasma PF-07817883 PK Parameters for PART-1: SAD, PART-3: 
RBA/FE, PART-4: ME and PART-6: SE, Midazolam PK Parameters in 
PART-5: DDI, and Moxifloxacin PK Parameters in PART-6: SE
Parameter
Part of the 
Study
Definition
Method of Determination
Cmaxc
1, 3, 4, 5, 6
Maximum plasma concentration
Observed directly from data
Tmaxc
1, 3, 4, 5, 6
Time for Cmax
Observed directly from data as 
time of first occurrence
t½b
1, 3, 4, 5, 6
Terminal half-life
Loge(2)/kel, 
where kel is the terminal phase 
rate constant calculated by a 
linear regression of the log-linear 
concentration-time curve. Only 
those data points judged to 
describe the terminal log-linear 
decline are used in the regression.
CL/Fb
1, 3, 4, 5, 6
Apparent clearance
Dose/AUCinf
Vz/Fb
1, 3, 4, 5, 6
Apparent volume of distribution
Dose/(AUCinf • kel)
AUClast(dn)
1
Dose normalized AUClast
AUClast/Dose
AUCinf(dn)b
1
Dose normalized AUCinf
AUCinf/Dose
Cmax(dn)
1
Dose normalized Cmax
Cmax/Dose
a.
In PART-5, Sequence 1, Day 1, 0h sample of midazolam in Period 2 will be considered as 48h PK for Period 1.
b.
If data permit.
c.
Only selected PK parameters to be calculated for moxifloxacin in PART-6
dn=dose normalized to a 1 mg dose.
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Table 18.
Plasma and Urine PF-07817883 PK Parameters for PART-2: MAD and 
PART-5: DDI
Parameter
Day(s)a
Definition
Method of Determination
Plasma
AUCτ
1, 5, 10
Area under the plasma concentration-
time profile from time 0 to time tau (τ), 
the dosing interval, where τ = 12 hours 
Linear/Log trapezoidal method
Cmax
1, 5, 10
Maximum plasma concentration during 
the dosing interval
Observed directly from data
Tmax
1, 5, 10
Time for Cmax
Observed directly from data as time of 
first occurrence
C12
5, 10
Concentration at 12h nominal time 
post-dose
Observed directly from data
PTR
5, 10
Peak-to-trough ratio
Cmax/Cmin
Rac
5, 10
Observed accumulation ratio for AUCτ
Day 5 or Day 10 AUCτ/Day 1 AUCτ
Rac,Cmax
5, 10
Observed accumulation ratio for Cmax
Day 5 or Day 10 Cmax/Day 1 Cmax
CL/F
5, 10
Apparent clearance
Dose/AUCτ
t½b
10
Terminal half-life
Loge(2)/kel, 
where kel is the terminal phase rate 
constant calculated by a linear 
regression of the log-linear 
concentration-time curve. Only those 
data points judged to describe the 
terminal log-linear decline are used in 
the regression
Vz/Fb
10
Apparent volume of distribution
Dose/(AUCτ • kel)
AUCτ(dn)
1, 5, 10
Dose normalized AUCτ
AUCτ/Dose
Cmax(dn)
1, 5, 10
Dose normalized Cmax
Cmax/Dose
Cav
1, 5, 10
Average concentration 
AUCτ/12
Urinec
Aeτ
10
Amount excreted in urine as unchanged 
drug over the dosing interval τ
Sum of (urine volume × urine 
concentration) for each collection over 
the dosing interval 
Aeτ%
10
Percent of dose excreted in urine as 
unchanged drug over the dosing interval 
τ
100 * Aeτ/Dose
CLr
10
Renal clearance
Aeτ/AUCτ
a.
Day 5 optional for PART-5.
b.
If data permit.
c.
Urine parameters are not applicable for PART-5.
dn=dose normalized to a 1 mg dose.
9.3.3.2. Statistical Methods for PK Data 
No formal inferential statistics will be applied to the plasma PK data apart from the 
comparisons of formulation and FE in either PART-1 or PART-3 and the estimation of the 
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effect of steady-state PF-07817883 on the PK of midazolam in PART-5. The PK data for 
PF-07817883 and Midazolam (PART-5) will be reported separately.
For all parts of the study, plasma concentrations of each analyte will be listed and 
summarized descriptively by PK sampling time and treatment. Individual participant and 
median profiles of the concentration-time data will be plotted by treatment. For summary 
statistics and median 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 for plasma 
samples. Median profiles will be presented on both linear-linear and log-linear scales.
In each part, the plasma and urine PK parameters of each analyte listed in Table 17 and
Table 18 will be summarized descriptively by Treatment and/or dose.
For PART-3, natural log transformed AUClast, Cmax, and AUCinf (if data permit) for 
PF-07817883 will be analyzed using a mixed effect model with sequence, period, and 
treatment included as fixed effects and participant nested within sequence as a random effect. 
Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs will 
be obtained from the model. The adjusted mean differences and 90% CIs for the differences 
will be exponentiated to provide estimates of the ratio of adjusted geometric means 
(Test/Reference) and 90% CIs for the ratios. Only the first 3 periods will be used in this 
analysis (ie, Fed formulations excluded).
To compare the Fed and Fasted formulations , natural log transformed AUClast, Cmax, and 
AUCinf (if data permit) for PF-07817883 from these two formulations will be analyzed 
separately using a paired t-test. Resulting estimates of the mean differences (Test -
Reference) and corresponding 90% CIs from the t-test will be exponentiated to provide 
estimates of the ratio of geometric means (Test/Reference) and 90% CIs for the ratios. 
Formulation Fasted is the Reference treatment and Formulation Fed is the Test treatment.
The following comparisons will be made (where applicable):
Comparison
Test
Reference
Formulation
PF-07817883 Oral Formulation 1 in Fasted 
state
PF-07817883 Oral Suspension in Fasted state (A)
PF-07817883 Oral Formulation 2 in Fasted 
state
PF-07817883 Oral Suspension in Fasted state (A)
FE
PF-07817883 Oral Formulation 1 in Fed 
(high fat high-calorie meal) state
PF-07817883 Oral Formulation 1 in Fasted state
PF-07817883 Oral Formulation 2 in Fed 
(high fat high-calorie meal) state
PF-07817883 Oral Formulation 2 in Fasted state
For PART-5, natural log transformed AUClast, Cmax and AUCinf (if data permit) of midazolam 
will be analyzed using a mixed effect model with sequence, period and treatment as fixed 
effects and participant nested within sequence as a random effect. Estimates of the adjusted 
mean differences (Test-Reference) and corresponding 90% CIs will be obtained from the 
model. The adjusted mean differences and 90% CIs for the differences will be exponentiated 
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to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs
for the ratios. Midazolam alone is the Reference treatment whilst midazolam + PF-07817883 
is the Test treatment.
If the number of Chinese or Japanese participants in PART-5 are ≥3 within a cohort, the 
plasma concentration and PK parameters of PF-07817883 may also be summarized 
separately for Chinese, Japanese and Western population. 
Specifications about the tables, listings, and figures will be outlined in the SAP.
9.3.4. Tertiary/Exploratory Endpoint(s) Analysis
Exploratory endpoints may not be reported in the CSR and may be reported separately. 
9.3.5. Safety Analyses
In this study, assessment of safety and tolerability forms the primary objective for PART-1,
PART-2 and PART-6. In all 6 parts of the study, all safety analyses will be performed on the 
Safety Analysis Set as defined in Section 9.2.
AEs, ECGs, BP, PR, continuous cardiac monitoring, and safety laboratory data, as 
applicable, will be reviewed and summarized on an ongoing basis during the study to 
evaluate the safety of participants. Any clinical laboratory, ECG, BP, and PR 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 PE 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 conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE. 
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted. Demographic data collected at screening will be reported.
9.3.5.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, HR, QTcF interval, PR interval, 
and QRS complex will be summarized by treatment and time.
The number (%) of participants with maximum postdose QTcF values and maximum 
increases from baseline in the following categories will be tabulated by treatment: 
Safety QTcF Assessment
Degree of Prolongation
Mild (ms)
Moderate (ms)
Severe (ms)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
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If more than 1 ECG is collected at a nominal time after dose administration (for example, 
triplicate ECGs), the mean of the replicate measurements will be used to represent a single 
observation at that time point. If any of the 3 individual ECG tracings has a QTcF value 
>500 ms, but the mean of the triplicates is not >500 ms, the data from the participant’s 
individual tracing will be described in a safety section of the CSR in order to place the 
>500-ms value in appropriate clinical context. However, values from individual tracings 
within triplicate measurements that are >500 ms will not be included in the categorical 
analysis unless the average from the triplicate measurements is also >500 ms. Changes from 
baseline will be defined as the change between the postdose QTcF value and the average of 
the time-matched baseline triplicate values on Day -1, or the average of the predose triplicate 
values on Day 1.
In addition, an attempt will be made to explore and characterize the relationship between 
plasma concentration and QT interval length using a PK/PD modeling approach. If a PK/PD 
relationship is found, the impact of participant factors (covariates) on the relationship may be 
examined.
9.3.6. Other Analyses 
9.3.6.1. Taste Assessment 
If done, the data collected for taste assessment using the sponsor-provided taste questionnaire 
will be numerically derived by measuring length (using a scale with gradations of at least 
0.1 centimeter) of the “x” marked by the participant relative to the “good trait”. The taste 
attributes from the taste questionnaires (Appendix 9) will be listed and descriptively 
summarized and appropriate plots may be generated.
The summary and analysis of the taste assessments may not be reported in the CSR.
9.3.6.2. Pharmacogenomic/Biomarker Assessment 
Pharmacogenomic or biomarker data from Retained Research Samples 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.
9.4. Interim Analyses
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor will conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating dose escalation decisions, facilitating PK modeling, 
and/or supporting clinical development. Unblinded results will be reviewed by a designated 
limited number of sponsor colleagues within the study team.
9.5. Sample Size Determination
A total of up to 122 participants (16 in PART-1: SAD, up to 36 [with 2 cohorts and 
4 optional cohorts] in PART-2: MAD, 12 in PART-3: RBA/FE cohort, 6 in PART-4: ME, up 
to 28 [with 2 cohorts of 14 each] in PART-5: DDI and 24 in PART-6: SE) are planned to be 
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enrolled in this study. Participants who discontinue for reasons other than safety during the 
study may be replaced at the discretion of the sponsor and Investigator.
9.5.1. PART-1: SAD
A sample size of 8 participants per cohort for this single, dose escalating, 3-period 
cross-over, with placebo substitution study (6 active, 2 placebo per dose level) has been 
chosen based on the need to minimize exposure of healthy participants to a new chemical 
entity and the requirement to provide adequate safety and toleration information and PK 
information at each dose level.
9.5.2. PART-2: MAD
A sample size of 6 participants per cohort, with 4 participants randomized to PF-07817883
plus 2 participants to placebo per cohort, has been selected as a compromise between the 
need to minimize exposure to PF-07817883 and the need to have sufficient participants 
randomized to provide adequate safety and toleration information and PK. 
This sample size has been judged sufficient to obtain a preliminary evaluation of safety, 
tolerability, and PK data in these populations. 
9.5.3. PART-3: RBA/FE
A sample size of 12 participants will provide adequate precision to compare the relative 
bioavailability of a solid oral formulation(s) of PF-07817883 relative to oral suspension, 
based on estimates of the within-participant standard deviations of 
for loge AUClast, 
for loge Cmax and
 for loge AUCinf using preliminary data from 150 mg, 
500 mg, 1500 mg, 3000 mg and 4000 mg fasted doses in Cohorts 1 and 2 from PART-1: 
SAD. The expected widths of the 90% CIs with 80% coverage probability for the comparison 
of tablet formulation of PF-07817883 relative to oral suspension are shown in Table 19 or a 
range of possible effects.
Table 19.
Expected Widths of the 90% CIs (with 80% Coverage Probability) for 
Different Possible Estimated Effects for AUClast, Cmax and AUCinf
Parameter
SD
Estimated Effect
Probable 90% CI
Probable CI 
Width
AUClast
AUCinf
Cmax
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9.5.4. PART-4: ME
A sample size of approximately 6 male participants (with at least 4 completers) is chosen 
based on the industry standard sample size for ME studies. This sample size was not justified 
by any empirical data or hypothesis testing criteria.
9.5.5. PART-5: DDI
A sample size of 12 participants has been selected to provide sufficient precision to detect a 
1.25-fold difference in Midazolam AUCinf. A total of 14 participants will be randomized to 
ensure that at least 12 participants complete the study. The following table presents the width 
of 90% confidence interval for different estimated effects:
Table 20.
Expected Widths of the 90% CIs (with 80% Coverage Probability) for 
Different Possible Estimated Effects for AUCinf
Parameter
Estimated Effect 
(100*Test/Reference)
90% CI*
CI Width*
AUCinf
50%
40% to 62%
22%
80%
64% to 100%
35%
90%
72% to 112%
40%
100%
80% to 125%
44%
125%
100% to 156%
55%
150%
120% to 187%
66%
* Rounded values.
These calculations are based on estimates of within‑participant coefficient of variation of
26% for loge AUCinf (midazolam), as obtained from the Pfizer Clinical Pharmacology
Guidance. The estimate of standard deviation of 0.256 for loge AUCinf was derived from 
within‑participant coefficient of variation.
9.5.6. PART-6: SE 
A sample size of approximately 24 participants will provide at least 87% power to 
demonstrate assay sensitivity for C-QTc modeling with pre-dose baseline as reported in 
Huang et al (2021).12
Additionally, a sample size of approximately 24 participants will provide at least 94% power 
to detect at least a 5 ms difference for QTcF between moxifloxacin and placebo at 
moxifloxacin Tmax of 3 hours (to demonstrate study sensitivity) when the true difference is 10 
ms. The statistical calculations were based on a 1-sided 5% paired t-test, assuming a common 
standard deviation of 5.35 ms for QTcF, according to the sponsor’s historical data. 
Garnett et al (2016)13 reported that the “false negative” rate (the upper bound of 90% interval 
less than 10 ms) using C-QTc modeling approach was 2-6% in crossover design trials with 
up to 24 participants for a true ΔΔQTcF of 10 ms at a supratherapeutic concentration. For 
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scenarios with small mean effect size, the power to exclude 10 ms was increased with 
increasing sample size, and approximately 80% in crossover studies with 24 participants, 
when the true mean effect was 5 ms.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
!
Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;
!
Applicable ICH GCP guidelines;
!
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:
!
Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;
!
Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;
!
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies, European Medical Device Regulation 2017/745 for 
clinical device research, and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Informed Consent Process
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participant and answer all questions regarding the 
study. The participant should be given sufficient time and opportunity to ask questions and to 
decide whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each 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 their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about their
right to access and correct their personal data and to withdraw consent for the processing of 
their personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations.
A copy of the ICD(s) must be provided to the participant.
A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 10 days from the previous ICD signature date.
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10.1.3. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to their actual identity and medical record ID. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access.
The sponsor maintains standard operating procedures on how to respond in the event of 
unauthorized access, use, or disclosure of sponsor information or systems.
10.1.4. Committees Structure
10.1.4.1. Data Monitoring Committee 
This study will not use an E-DMC.
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/CTIS, and/or 
www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
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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/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable 
information anonymized.
Documents within marketing applications
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
Data sharing
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
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Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study-critical data items and 
processes (eg, risk-based initiatives in operations and quality, such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan maintained 
and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
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10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the 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 and its origin can be found in the Source 
Document Locator, which is maintained by the sponsor’s designee (Pfizer CRU).
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor’s designee (Pfizer CRU).
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The sponsor or designee will perform monitoring to confirm that data entered into the CRF
by authorized site personnel are accurate, complete, and verifiable from source documents; 
that the safety and rights of participants are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.8. 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, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. Study sites will be closed upon study completion. A study site is considered 
closed when all required documents and study supplies have been collected and a study-site 
closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.
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Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:
!
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor’s procedures, or the ICH GCP 
guidelines;
!
Inadequate recruitment of participants by the investigator;
!
Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Sponsor’s Medically Qualified Individual
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the CTMS. 
To facilitate access to their investigator and the sponsor’s MQI for study-related medical 
questions or problems from nonstudy healthcare professionals, participants are provided with 
an ECC at the time of informed consent. The ECC contains, at a minimum, (a) protocol and 
study intervention identifiers, (b) participant’s study identification number, and (c) site 
emergency phone number active 24 hours/day, 7 days per week.
The ECC is intended to augment, not replace, the established communication pathways 
between the participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. 
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety issues.
Table 21.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
Cystatin-Cg and eGFR
(2021 CKD-EPI)h
CK
pHf
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopy and 
culturea
!
Urine drug screeningc
!
SARS-CoV-2 RT-PCR
!
Pregnancy test (#-hCG)d
!
aPTT
!
PT
!
INR
!
Amylase
!
Lipase
At screening only:
!
FSHb
!
HBsAg
!
HBsAbe
!
HBcAb
!
HCVAb
!
HIV
a.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase. Urinary culture only 
if deemed appropriate by the investigator.
b.
For confirmation of postmenopausal status only (post-menopausal females only), at screening only.
c.
The minimum requirement for drug screening includes cocaine, THC, opiates/opioids, benzodiazepines, 
and amphetamines (others are site and study specific).
d.
Serum pregnancy test required at screening. Serum or urine #–hCG for female participants of 
childbearing potential.
e.
Can be done either automatically or only if HBcAb or HBsAg is positive, as per local practices.
f.
Can be performed on dipstick or pH meter device.
g.
Cystatin-C to be performed at baseline (Day -1 at time of admission), then repeated as deemed 
appropriate by the investigator. 
h.
Age-specific kidney function calculation as specified in Section 10.7.2.
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.
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 
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 an 
increase in either frequency and/or intensity of the condition.
!
New condition detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study.
!
Signs, symptoms, or the clinical sequelae of a suspected DDI.
!
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 or 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 that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.
!
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.
!
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.
!
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
!
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.
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d. Results in persistent or significant disability/incapacity
!
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
!
This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or non-pathogenic 
The event may be suspected from clinical symptoms or laboratory findings indicating 
an infection in a participant exposed to a Pfizer product. The terms “suspected 
transmission” and “transmission” are considered synonymous. These cases are 
considered unexpected and handled as serious expedited cases by pharmacovigilance 
personnel. Such cases are also considered for reporting as product defects, if 
appropriate.
g. Other situations:
!
Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant 
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.
!
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the CT SAE Report Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; 
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(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.
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
All AEs/SAEs associated 
with EDP or EDB
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE)**
Environmental or 
occupational exposure to 
the product under study 
to a nonparticipant (not 
involving EDP or EDB)
None. Exposure to a study 
non-participant is not 
collected on the CRF
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported***
*
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer 
Safety using the CT SAE Report Form and EDP Supplemental Form; if the EDP is associated with 
an SAE, then the SAE is reported to Pfizer Safety using the CT SAE Report Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form, which would also include details 
of any SAE that might be associated with the EDB. 
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety using the CT SAE Report Form. 
!
When an AE or 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 or SAE information in the CRF.
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!
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE or SAE 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 or 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: A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usual ADL.
!
Moderate: A type of AE that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual ADL, causing discomfort,
but poses no significant or permanent risk of harm to the research participant.
!
Severe: A type of AE that interrupts usual ADL, or significantly affects clinical 
status, or may require intensive therapeutic intervention.
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 or SAE. The investigator will use clinical 
judgment to determine the relationship.
!
A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.
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!
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.
!
The investigator will also consult the IB and/or product information, for marketed 
products, in their assessment.
!
For each AE or SAE, the investigator must document in the medical notes that they 
have reviewed the AE or SAE and have 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 their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.
!
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
!
If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor. In addition, if the investigator determines that 
an SAE is associated with study procedures, the investigator must record this 
causal relationship in the source documents and 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.
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!
New or updated information will be recorded in the originally submitted 
documents.
!
The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic DCT
!
The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic DCT.
!
If the electronic system is unavailable, then the site will use the paper SAE DCT
(see next section) to report the event within 24 hours.
!
The site will enter the SAE data into the electronic DCT (eg, eSAE or PSSA) or 
paper form (as applicable) as soon as the data become available.
!
After the study is completed at a given site, the electronic DCT will be taken 
off-line to prevent the entry of new data or changes to existing data.
!
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic DCT 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 the 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, an alternative method should 
be used, eg, secured (Transport Layer Security) or password-protected email. If 
none of these methods can be used, 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 and Barrier Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s): 
!
Refrain from donating sperm.
PLUS either:
!
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
!
Must agree to use contraception/barrier as detailed below:
!
Agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception, as a condom 
may break or leak, when having sexual intercourse with a WOCBP who is not 
currently pregnant.
!
In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants as described in Section 10.4.4.
10.4.2. Female Participant Reproductive Inclusion Criteria
The criteria below are part of Inclusion Criterion 1 (Age and Sex; Section 5.1) and specify 
the reproductive requirements for including female participants. Refer to Section 10.4.4 for a 
complete list of contraceptive methods permitted in the study. 
A female participant is eligible to participate if she (a) is not pregnant or breastfeeding;
(b) agrees to not donate eggs (ova, oocytes) for the purpose of reproduction and (c) at least 1
of the following conditions applies:
!
Is not a WOCBP (see definition in Section 10.4.3).
OR
!
Is a WOCBP who agrees to use a highly effective contraceptive method (failure rate 
of <1% per year) with low user dependency during the intervention period and for at 
least 28 days after the last dose of study intervention, which corresponds to the time 
needed to eliminate any reproductive safety risk of the study intervention(s). The 
investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention.
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OR
!
Is a WOCBP and agrees to use a highly effective (failure rate of <1% per year) 
user-dependent method of contraception during the intervention period and for at 
least 28 days after the last dose of study intervention, which corresponds to the time 
needed to eliminate any reproductive safety risk of the study intervention(s). In 
addition to her use of the highly effective method above, she agrees to concurrently
use an effective barrier method. The investigator should evaluate the effectiveness of 
the contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for reviewing the woman’s medical history, menstrual history,
and recent sexual activity in order to decrease the risk of enrolling a woman with an early, 
undetected pregnancy.
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:
!
Documented hysterectomy;
!
Documented bilateral salpingectomy;
!
Documented bilateral oophorectomy.
For individuals with permanent infertility due to a medical cause other than the above
(eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female.
!
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition:
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!
A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 
!
A female on HRT and whose menopausal status is in doubt will be required to 
use one of the highly effective nonestrogen hormonal contraception methods 
if she wishes to continue her HRT during the study. Otherwise, she must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
The following contraceptive methods are appropriate for this study:
Highly Effective Methods That Have Low User Dependency 
1. Intrauterine device.
2. Intrauterine hormone-releasing system.
3. Bilateral tubal occlusion.
4. Vasectomized partner.
!
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent 
5. Sexual Abstinence.
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
Highly Effective Methods That Have Low User Dependency (for WOCBP partners of male 
participants) 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
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2. Intrauterine device.
3.
Intrauterine hormone-releasing system. 
4. Bilateral tubal occlusion. 
5. Vasectomized partner.
!
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days. 
Highly Effective Methods That Are User Dependent (for WOCBP partners of male 
participants) 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: 
!
Oral + barrier*; 
!
Intravaginal+ barrier*; 
!
Transdermal+ barrier*. 
7. Progestogen-only hormone contraception associated with inhibition of ovulation: 
!
Oral+ barrier*; 
!
Injectable+ barrier*. 
8. Sexual Abstinence.
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
* Acceptable barrier methods to be used concomitantly with options 6 or 7 for the study 
include any of the following:
!
Male or female condom with or without spermicide;
!
Cervical cap, diaphragm, or sponge with spermicide;
!
A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).
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10.5. Appendix 5: Genetics
Use/Analysis of DNA
!
Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis.
!
The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.
!
The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to PF-07817883 or study interventions of this class to 
understand treatments for the disease(s) under study or the disease(s) themselves.
!
The results of genetic analyses may be reported in the CSR or in a separate study 
summary, or may be used for internal decision making without being included in a 
study report.
!
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
!
The samples will be retained as indicated:
!
Retained samples will be stored indefinitely or for another period as per local 
requirements. 
!
Participants may withdraw their consent for the storage and/or use of their Retained 
Research Samples at any time by making a request to the investigator; in this case, 
any remaining material will be destroyed. Data already generated from the samples 
will be retained to protect the integrity of existing analyses. 
!
Samples for genetic research will be labeled with a code. The key between the code 
and the participant’s personally identifying information (eg, name, address) will be 
held securely at the study site. 
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
“susceptible” to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede T bili elevations 
(>2 × ULN) by several days or weeks. The increase in T bili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and T bili values will be 
elevated within the same laboratory sample). In rare instances, by the time T bili elevations 
are detected, AST/ALT values might have decreased. This occurrence is still regarded as a 
potential DILI. Therefore, abnormal elevations in either AST OR ALT in addition to T bili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:
!
Participants with AST/ALT and T bili baseline values within the normal range who 
subsequently present with AST OR ALT values ≥3 × ULN AND a T bili value 
≥2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.
!
For participants with baseline AST OR ALT OR T bili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
!
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values ≥2 times the baseline values AND ≥3 × ULN; or ≥8 × ULN (whichever is 
smaller).
!
Preexisting values of T bili above the normal range: T bili level increased from 
baseline value by an amount of ≥1 × ULN or if the value reaches ≥3 × ULN 
(whichever is smaller).
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Rises in AST/ALT and T bili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and T bili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
T bili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.7. Appendix 7: Kidney Safety: Monitoring Guidelines
10.7.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury
Standard kidney safety monitoring requires assessment of baseline and postbaseline serum 
creatinine (SCr measurement to estimate glomerular filtration rate [SCr-based eGFR] or 
creatinine clearance [eCrCl]). Baseline and postbaseline serum Scys makes it feasible to 
distinguish AKI from other causes of SCr increase. If SCr increase is confirmed after 
baseline, then reflex measurement of Scys is indicated to estimate the combined SCr-Scys 
eGFR calculation (for adults only).
Regardless of whether kidney function monitoring tests are required as a routine safety 
monitoring procedure in the study, if the investigator or sponsor deems it necessary to further 
assess kidney safety and quantify kidney function, then these test results should be managed 
and followed per standard of care.
10.7.2. Age-Specific Kidney Function Calculation Recommendations
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations14
2021 CKD-
EPI 
SCr Only
SCr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤0.7
NA
eGFR = 143 × (SCr/0.7)-0.24 × (0.9938)Age
Female
if >0.7
NA
eGFR = 143 × (SCr/0.7)-1.200 × (0.9938)Age
Male
if ≤0.9
NA
eGFR = 142 × (SCr/0.9)-0.302 × (0.9938)Age
Male
if >0.9
NA
eGFR = 142 × (SCr/0.9)-1.200 × (0.9938)Age
2021 CKD-
EPI 
SCr-Scys 
Combined
SCr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤0.7
if ≤0.8
eGFR = 130 × (SCr/0.7)-0.219 × (Scys/0.8)-0.323 × (0.9961)Age
Female
if ≤0.7
if >0.8
eGFR = 130 × (SCr/0.7)-0.219 × (Scys/0.8)-0.778 × (0.9961)Age
Female
if >0.7
if ≤0.8
eGFR = 130 × (SCr/0.7)-0.544 × (Scys/0.8)-0.323 × (0.9961)Age
Female
if >0.7
if >0.8
eGFR = 130 × (SCr/0.7)-0.544 × (Scys/0.8)-0.778 × (0.9961)Age
Male
if ≤0.9
if ≤0.8
eGFR = 135 × (SCr/0.9)-0.144 × (Scys/0.8)-0.323 × (0.9961)Age
Male
if ≤0.9
if >0.8
eGFR = 135 × (SCr/0.9)-0.144 × (Scys/0.8)-0.778 × (0.9961)Age
Male
if >0.9
if ≤0.8
eGFR = 135 × (SCr/0.9)-0.544 × (Scys/0.8)-0.323 × (0.9961)Age
Male
if >0.9
if >0.8
eGFR = 135 × (SCr/0.9)-0.544 × (Scys/0.8)-0.778 × (0.9961)Age
10.7.3. Adverse Event Grading for Kidney Safety Laboratory Abnormalities
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to KDIGO
criteria.
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10.8. Appendix 8: 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 ms.
!
New prolongation of QTcF to >480 ms (absolute) or by ≥60 ms 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 ms.
!
New ST-T changes suggestive of myocardial ischemia.
!
New-onset LBBB (QRS complex>120 ms).
!
New-onset right bundle branch block (QRS complex>120 ms).
!
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 (HR
<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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10.10. Appendix 10: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
ACE2
angiotensin-converting enzyme 2
ADL
activity/activities of daily living
AE
adverse event
Aetau; Aeτ
amount excreted in urine as unchanged drug over the dosing 
interval τ/tau
Aetau%; Aeτ%
percent of dose excreted in urine as unchanged drug over the 
dosing interval τ/tau
AESI
adverse events of special interest
AKI
acute kidney injury
ALT
alanine aminotransferase
API
active pharmaceutical ingredient
aPTT
activated partial thromboplastin time
ARDS
acute respiratory distress syndrome
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC24
area under the plasma concentration-time profile from time 0
to the time 24 hours
AUC24,ss
area under the plasma concentration-time profile from time 0
to the time 24 hours at steady-state
AUCinf
area under the plasma concentration-time curve from time 0
extrapolated to infinite time
AUCinf(dn)
dose normalized AUCinf
AUClast
area under the plasma concentration time curve from time 0 
to the time of the last quantifiable concentration
AUClast(dn)
dose normalized AUClast
AUCτ; AUCtau
area under the plasma concentration-time profile from time 0
to time tau (τ), the dosing interval
AUCτ(dn); AUCtau(dn)
dose normalized AUCτ
AV
atrioventricular
AxMP
auxiliary medicinal product
BBS
Biospecimen Banking System
BCRP
breast cancer resistance protein
#–hCG
beta-human chorionic gonadotropin
BID
twice daily
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BR
Brussels
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Abbreviation
Term
BUN
blood urea nitrogen
C12
concentration at 12h nominal time post-dose
Cav
average concentration
Ceff
efficacious concentration
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
chronic kidney disease epidemiology collaboration
CL
clearance
Clast
last quantifiable concentration
CL/F
apparent clearance
CLr
renal clearance
Cmax
maximum plasma concentration
Cmax(dn) 
dose normalized Cmax
Cmax,ss
maximum plasma concentration at steady-state
Cmin
minimum observed concentration
CO2
carbon dioxide (bicarbonate)
COVID-19
Coronavirus disease 2019
CP-I
Coproporphyrin I
CP-III
Coproporphyrin III
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
Clinical Study Report
CT
clinical trial
CTIS
Clinical Trial Information System
CTMS
clinical trial management system
CYP
cytochrome P450
DCT
data collection tool
DDI
drug-drug interaction
DILI
drug-induced liver injury
DNA
deoxyribonucleic acid
dNHBE
differentiated normal human bronchial epithelial
D#
Dose#
DR#
dosing regimen#
EC
ethics committee
EC50
half maximal effective concentration
EC90
90% maximal effective concentration
ECG
electrocardiogram
eCrCl
estimated creatinine clearance
eCRF
electronic case report form
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Abbreviation
Term
EDB
exposure during breastfeeding
E-DMC
External Data Monitoring Committee
EDP
exposure during pregnancy
EDR
extemporaneous dispensing record
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
eSAE
electronic serious adverse event
E/T
early termination
EU
European Union
EUA
Emergency Use Authorization
EudraCT
European Union Drug Regulating Authorities Clinical Trials 
(European Clinical Trials Database)
FDA
Food and Drug Administration
FE
food effect
FIH
first-in-human
19F-NMR
fluorine-19 nuclear magnetic resonance
FSH
follicle-stimulating hormone
fu
free fraction
F/U
follow-up
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GLP
Good Laboratory Practice
HAE
human airway epithelial
HBcAb
hepatitis B core antibody
HBsAg 
hepatitis B surface antigen
HCoV-229E
Human coronavirus 229E
HCV
hepatitis C virus
HCVAb
hepatitis C antibody
HED
human equivalent dose
HIV
human immunodeficiency virus
HLM
human liver microsome
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator’s Brochure
IBC
Isobutyrylcarnitine
IC50
inhibitory concentration 50%
ICD
Informed Consent Document
ICH
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use
ID
identification
IMP
investigational medicinal product
IND
Investigational New Drug 
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Abbreviation
Term
INR
international normalized ratio
IPAL
Investigational Product Accountability Log
IRB
Institutional Review Board
IV
intravenous(ly)
KDIGO
Kidney Disease Improving Global Outcomes
kel
first-order elimination rate constant
KO
knockout
LBBB
left bundle branch block
LFT
liver function test
mAB
monoclonal antibody
MAD
multiple ascending dose
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDR1
multidrug resistance mutation 1
ME
Metabolism and Excretion
MERS-CoV
Middle East Respiratory Syndrome Coronavirus
MPro
main protease
MQI
medically qualified individual
NA
not applicable
NH
New Haven
NH CRU
New Haven clinical research unit
NHP
non-human primates
NIMP
non-investigational medicinal product
NOAEL
no observed adverse effect level
NYHA
New York Heart Association
OATP
organic anion transporting polypeptides
Papp
apparent permeability coefficient
PBPK
physiology based pharmacokinetic
PD
pharmacodynamic(s)
PE
physical examination
P-gp
p-glycoprotein
PI
Primary Investigator
PK
pharmacokinetic(s)
PL
placebo
PR
pulse rate
PSSA
Pfizer’s Serious Adverse Event Submission Assistant
PT
prothrombin time
PTR
peak-to-trough ratio
PVC
premature ventricular contraction
QTc
corrected QT interval
QTcF
corrected QT interval using Fridericia’s formula
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Abbreviation
Term
qual
qualitative
Rac
observed accumulation ratio for AUCτ
Rac,Cmax
observed accumulation ratio for Cmax
RBA
relative bioavailability
RBC
red blood cell
RNA
ribonucleic acid
RT-PCR
reverse transcription polymerase chain reaction
SAD
single ascending dose
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-1
Severe Acute Respiratory Syndrome Coronavirus 1
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
SARS-CoV-2 Mpro
the main protease of SARS-CoV-2
SCr
serum creatinine
Scys
serum cystatin C
SD
single dose; standard deviation
SDD
spray dried dispersion
SE
supratherapeutic exposure
SmPC
Summary of Product Characteristics
SMQ
Standardized MedDRA Query
SoA
schedule of activities
SOP
standard operating procedure
SRSD
Single Reference Safety Document
SUSAR
Suspected Unexpected Serious Adverse Reaction
t½
terminal half-life
TBD
to be determined
T bili
total bilirubin
TEAE
treatment-emergent adverse events
THC
tetrahydrocannabinol
Tmax
time for Cmax
UK
United Kingdom
ULN
upper limit of normal
US
United States
USPI
United States Prescribing Information
UV-Vis
ultraviolet-visible spectroscopy
Vss
steady-state volume of distribution
Vz/F
apparent volume of distribution
WBC
white blood cell
WHO
World Health Organization
WOCBP
woman/women of childbearing potential
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10.11. Appendix 11: Protocol Amendment History
The protocol amendment summary of changes table for the current amendment is located 
directly before the Table of Contents. The protocol amendment summary of changes tables 
for past amendment(s) can be found below:
Document
Version Date
Summary of Changes and Rationale
Amendment 2 11 January 
2023
Section 1.1 Synopsis: The synopsis was aligned with 
the remainder of the protocol: PART-6 was added to 
objectives and endpoints; Overall Design was 
amended to reflect changes in PART-5 and the 
addition of PART-6; Number of Participants was 
updated to reflect the changes to PART-5 and 
addition of PART-6; Exclusion Criteria were updated
with key criteria specific to PART-6; Study 
Interventions Table was updated to add Moxifloxacin 
for PART-6; PART-6 was included in Statistical 
Methods.
Section 1.2.5: An optional Cohort 12 was added to 
the schema for PART-5 to potentially evaluate the 
effect of steady-state PF-07817883 at lower dose on 
the PK of midazolam in healthy adult participants.
Section 1.2.6: Schema for PART-6 was added to 
evaluate safety, tolerability and PK of PF-07817883
at SE.
Section 1.3.5: Changes were made to add the 
administration of PF-07817883 along with 5 mg 
midazolam on Day 5 in Treatment C for optional 
Cohort 12:
Sequence 1: Midazolam dose in Period 2 Day 5 was 
added for optional Cohort 12 only; 
Sequence 2: Midazolam dose in Period 1 Day 5 was 
added for optional Cohort 12 only.
Section 1.3.6: SoA (Table 9) for PART-6 was added
to provide the Schedule of Activities for Part-6.
Section 2.1: PART-6 was add to provide the study 
rationale.
Section 2.2.2; Section 2.2.2.1; Section 2.2.2.2: 
Clinical safety data for PF-07817883 was added to 
provide clinical safety updates based on the
preliminary data collected in PARTs 1 and 2 of this 
study.
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Document
Version Date
Summary of Changes and Rationale
Section 2.3.1: Risk assessment for moxifloxacin was 
added to provide potential risks related to the 
administration of moxifloxacin and the corresponding 
mitigation strategies.
Section 3: Section 3.6 was added to include 
objectives and endpoints for PART-6: SE.
Sections 4; 4.1.3; 4.1.5; 4.1.6: Text revised to reflect 
study design changes (removal of “optional”) in 
PARTS 3, 4, and 5. Added 4.1.6 to include PART-6.
Section 4.2.5: Scientific rationale for the optional 
Cohort 12 was provided.
Section 4.2.6: Scientific rationale for PART-6 was 
added.
Section 4.3: Added sections 4.3.2 to update the dose 
justification for PART-3, and 4.3.3 to include the 
dose justification for PF-07817883 and moxifloxacin 
in PART-6.
Section 5.2: Exclusion criteria for PART-6 were 
added in the subsections “Prior/Concomitant 
Therapy” and “Other Exclusion Criteria” to exclude 
participants at increased risk if dosed with 
moxifloxacin, and participants with history or risk 
factors for QT prolongation or torsades de pointes, 
congenital deafness, family history of sudden death, 
and family history of long QT syndrome.  
Section 5.3.2: Restriction was added for PART-6 
regarding the intake of ambient temperature or warm 
drinks from Day 1 until final ECG measurements 
have been collected in each study period for 
clarification purpose.
Section 5.3.4: Activity for PART-1 only was updated 
to be for both PART-1 and PART-6 to standardize 
ECG collection and continuous cardiac monitoring..
Section 6: Information related to moxifloxacin was 
added to provide information for moxifloxacin to be 
administrated in PART-6.
Section 6.1.1.6: Administration details for 
PF-07817883/placebo and moxifloxacin were added
to provide information for PF-07817883/placebo and 
moxifloxacin to be administrated in PART-6.
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Document
Version Date
Summary of Changes and Rationale
Section 6.2.1: Information related to moxifloxacin 
was added to provide information for moxifloxacin to 
be administrated in PART-6.
Section 8.3.3: Requirements for ECG collection and 
continuous cardiac monitoring in PART-6 were 
added to standardize ECG collection and continuous 
cardiac monitoring.
Section 8.5: A subsection (Section 8.5.3) was added 
for PK analysis of moxifloxacin to standardize the 
PK analysis of moxifloxacin in PART-6.
Section 9.2: Description for ECG analysis set was 
added for purpose of analysis.
Section 9.3.3.1.1: PF-07817883 and moxifloxacin
PK parameters in PART-6 were added for purpose of 
analysis.
Section 9.5: The number of cohort and/or participant 
in PARTs 1-5 was updated, and the justification for 
sample size in PART-6 was added to align with the 
current study design.
Sections 1.2.1-1.2.5: Corresponding cohort 
number(s) was added to PARTs 1-5 for clarification.
Section 9.3.5: The whole section was updated with 
addition of PART-6.
Various sections: Spelling corrections and other 
editorial changes were made.
Amendment 1
21 October 2022
Sections 1.3.1-2, and Section 8.3.1: Post-dose 
physical exam (neuromuscular) was included to 
augment safety monitoring in line with FDA 
requests.
Section 6.6.1: Dose escalation termination criterion 
based on neuromuscular exam was added and the 
dose escalation termination criterion for ECG was 
modified to augment safety monitoring in line with 
FDA requests.
Sections 4.2 & 10.2: CK, PT, aPTT, INR, amylase 
and lipase were added to safety lab assessments to 
augment safety monitoring in line with FDA 
requests.
Section 2.3.1: ECG was deleted.
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 176
Document
Version Date
Summary of Changes and Rationale
Brief Title of Section 1.1: “Mass Balance” was 
updated to “Metabolism and Excretion” to align with 
Brief Title in the Title Page.
Section 1.3 SOA: In Tables 1, 2, 4, 5, 6, and 7, 
SARS-CoV-2 RT-PCR only to be done at admission
to align with the current practice.
Sections 1.3.1-2: In Tables 1, 2, and 3, note for the 
row 12-Lead ECG (triplicate) was updated for 
clarification.
In Tables 1 and 2, the first note was updated for 
clarification.
Section 8.1: Total blood sampling volume was 
updated to allow additional safety labs.
Section 1.3.3: In Table 4, note for “Contraception 
check”, “Pregnancy test”, “SARS-CoV-2 RT-PCR” 
and “COVID-19 signs and symptoms” rows were 
modified for clarity.
Section 1.3.4: In Table 5, Day -1 was removed from 
the Drug related material measurement and metabolic 
profiling row as no need for testing at Day-1.
Section 5.2: In the subsection of medical conditions, 
the 2 bullets that start with “PART-5 only” were 
updated to Exclusion Criteria #4 and #5.
Section 5.3.2: In the subsection of Evening dosing 
condition, the text of “afternoon and/or” was 
removed as there is no afternoon dose
Section 6.1.1.3: The second sentence “At a time 
point when PF07817883” was removed.
Section 10.4.4: The paragraph below #5 Sexual 
Abstinence was updated to be a subsection of #5 
instead of being #6.
The below 2 sentences were underlined to keep 
consistent across the whole section:
Highly Effective Methods That Have Low User 
Dependency (for WOCBP partners of male 
participants)
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 177
Document
Version Date
Summary of Changes and Rationale
Highly Effective Methods That Are User Dependent 
(for WOCBP partners of male participants)
Section 10.4.4: Added missing text describing 
effective barrier methods that must be used.
Title Page and Section 1.1: ClinicalTrials.gov ID 
was added.
Section 5.3.2: Post-dose food restriction in fed state 
was changed to 4h to make it consistent with EU 
guidance.
Section 9.3.3.1.1: The PK parameters derivation for 
midazolam in PART-5 was defined in Table 14 to 
make it consistent with the title.
Section 8: Blood volume was changed to allow 
additional clinical lab tests.
Section 10.2: CKD-EPI formula was clarified.
Section 3.5: Midazolam PK parameters calculations 
were clarified.
Section 10.10: Added abbreviations appeared in
added text.
Various sections: Spelling corrections and other 
editorial changes were made.
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 178
11. REFERENCES
1.
WHO Situation Report 51. 11 March 2020 Available from: 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. 
Accessed: 29 March 2020.
2.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus 
disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from 
the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.
3.
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, 
and outcomes among 5700 patients hospitalized with COVID-19 in the New York City 
area. JAMA. 2020;323(20):2052-9.
4.
Docherty AB, Harrison EM, Green CA, et al. Features of 20-133 UK patients in 
hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: 
prospective observational cohort study. BMJ. 2020;369:1-12: m1985.
5.
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 
2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 
2020;323(11):1061-9.
6.
Pei G, Zhang Z, Peng J, et al. Renal Involvement and Early Prognosis in Patients with 
COVID-19 Pneumonia. J Am Soc Nephrol. 2020;31(6):1157-65.
7.
Nopp S, Moik F, Jilma B, et al. Risk of venous thromboembolism in patients with 
COVID-19: A systematic review and meta-analysis. Res Pract Thromb Haemost. 
2020;4(7):1178-91.
8.
Centers for Medicare & Medicaid Services. COVID-19 Monoclonal Antibodies. 
Available from: https://www.cms.gov/monoclonal . Updated 10 Aug 2022. Accessed: 
06 Sep 2022.
9.
National Institutes of Health. COVID-19 Treatment Guidelines. Coronavirus Disease 
2019 (COVID-19) Treatment Guidelines. Available at 
https://www.covid19treatmentguidelines.nih.gov/. Updated: 18 Aug 2022. Accessed: 
11 Aug 2022.
                                                
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)


PF-07817883
Protocol C5091001
Final Protocol Amendment 3, 09 Mar 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Pharmacology Protocol Template (01 April 2022)
Page 179
10.
Singh RSP, Walker GS, Kadar EP, et al. Metabolism and excretion of nirmatrelvir in 
humans using quantitative fluorine nuclear magnetic resonance spectroscopy: a novel 
approach for accelerating drug development. Clin Pharmacol Ther. 
2022;10.1002/cpt.2683.
11.
Ramsden D, Zhou J, Tweedie DJ. Determination of a Degradation Constant for 
CYP3A4 by Direct Suppression of mRNA in a Novel Human Hepatocyte Model, 
HepatoPac. Drug Metab Dispos. 2015;43(9):1307-15.
12
Huang DP, Chen J, Tsong Y. Baseline selection in concentration-QTc modeling: impact 
on assay sensitivity. J Biopharm Stat 2021;31(2):168-179. DOI: 
10.1080/10543406.2020.1814797
13
Garnett C, Needleman K, Liu J, Brundage R, Wang Y. Operational Characteristics of 
Linear Concentration-QT Models for Assessing QTc Interval in the Thorough QT and 
Phase I Clinical Studies. Clin Pharmacol Ther 2016;100(2):170-8. DOI: 
10.1002/cpt.361.
14
Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C-Based 
Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-49.
090177e19cda0704\Approved\Approved On: 09-Mar-2023 18:53 (GMT)

SAP_001.pdf: 
Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 of 5 5 
 
 
 
 
Pr ot oc ol C 5 0 9 1 0 0 1 
 
 
 
 
C O VI D - 1 9: A M U L TI P A R T, P H A S E 1 S T U D Y WI T H R A N D O MI Z E D, D O U B L E-
B LI N D, S P O N S O R - O P E N, P L A C E B O- C O N T R O L L E D, SI N G L E- A N D M U L TI P L E -
D O S E E S C A L A TI O N T O E V A L U A T E T H E S A F E T Y, T O L E R A BI LI T Y A N D 
P H A R M A C O KI N E TI C S O F P F - 0 7 8 1 7 8 8 3 A N D O P TI O N A L O P E N- L A B E L, 
R A N D O MI Z E D S T U D Y T O E V A L U A T E R E L A TI V E BI O A V AI L A BI LI T Y A N D 
F O O D E F F E C T O F  S O LI D O R A L F O R M U L A TI O N A N D O P TI O N A L O P E N -
L A B E L, N O N- R A N D O MI Z E D S T U D Y T O E V A L U A T E M E T A B O LI S M A N D 
E X C R E TI O N  O F P F - 0 7 8 1 7 8 8 3 A N D O P TI O N A L R A N D O MI Z E D, O P E N - L A B E L 
S T U D Y T O A S S E S S T H E E F F E C T O F P F- 0 7 8 1 7 8 8 3 O N P H A R M A C O KI N E TI C S O F 
MI D A Z O L A M I N H E A L T H Y A D U L T P A R TI CI P A N T S  
 
 
St atistic al A n al ysis Pl a n  
( S A P) 
 
 
 
 
 
 
 
V ersi o n :  
v 2. 0 
 
D ate:   
2 4 Ma y  2 0 2 3  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 of 5 5 
T A B L E O F C O N T E N T S 
T A B L E O F C O N T E N T S  ........................................................................................................... 2 
LI S T O F T A B L E S  ..................................................................................................................... 4 
LI S T O F FI G U R E S  ................................................................................................................... 4 
A P P E N DI C E S  ........................................................................................................................... 4 
1. V E R SI O N HI S T O R Y  ............................................................................................................ 6 
2. I N T R O D U C TI O N ................................................................................................................. 8  
2. 1. M o dificati o ns t o t he A nal ysis Pla n Descri be d i n t he Pr ot oc ol .................................. 8  
2. 2. St u d y O bjecti ves, E n d p oi nts, a n d Esti ma n ds  ............................................................ 8 
2. 3. St u d y Desi g n ........................................................................................................... 1 5  
2. 3. 1. O verall Desi g n  ............................................................................................ 1 5 
2. 3. 2. P A R T- 1: S A D  ............................................................................................. 1 5 
2. 3. 3. P A R T- 2: M A D  ........................................................................................... 1 5 
2. 3. 4. P A R T- 3: R B A/ F E ....................................................................................... 1 5  
2. 3. 5. P A R T -4: M E  ............................................................................................... 1 6 
2. 3. 6. P A R T- 5: D DI .............................................................................................. 1 6 
2. 3. 7. P A R T- 6: S E  ................................................................................................ 1 7 
2. 3. 8. N u m ber of Partici pa nts ............................................................................... 1 8  
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S:  D E FI NI TI O N S A N D 
C O N V E N TI O N S  ................................................................................................................ 2 2 
3. 1. Pri mar y E n d p oi nt(s) ................................................................................................ 2 2  
3. 2. Sec o n dar y E n d p oi nt(s) ............................................................................................ 2 2  
3. 3. Ot her E n d p oi nt(s) .................................................................................................... 2 2  
3. 3. 1. P har mac o ki netic ( P K) E n d p oi nts ............................................................... 2 2  
3. 4. Baseli ne Varia bles  ................................................................................................... 2 4 
3. 5. Safet y E n d p oi nts ..................................................................................................... 2 4  
3. 5. 1. A d verse E ve nts ........................................................................................... 2 4  
3. 5. 2. La b orat or y Data .......................................................................................... 2 4  
3. 5. 3. Vital Si g ns .................................................................................................. 2 5  
3. 5. 4. E C G ............................................................................................................ 2 6  
3. 6. Ot her E n d p oi nt(s) .................................................................................................... 2 6  
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S)  ................................................... 2 7 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 of 5 5 
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S  .................................................... 2 8 
5. 1. H y p ot heses a n d Decisi o n R ules .............................................................................. 2 8  
5. 2. Ge neral Met h o ds ..................................................................................................... 2 8  
5. 2. 1. A nal yses f or C o nti n u o us E n d p oi nts ........................................................... 2 8  
5. 2. 2. A nal yses f or Cate g orical E n d p oi nts ........................................................... 2 8  
5. 3. Met h o ds t o Ma na ge Missi n g Data .......................................................................... 2 8  
6. A N A L Y S E S A N D S U M M A RI E S  ...................................................................................... 2 9 
6. 1. Pri mar y E n d p oi nt(s) ................................................................................................ 2 9  
6. 2. Sec o n dar y E n d p oi nt(s) ............................................................................................ 2 9  
6. 3. Ot her E n d p oi nts ....................................................................................................... 3 2  
6. 3. 1. F o o d Effect i n P A R T- 1: S A D ..................................................................... 3 2 
6. 3. 2. P K Bi o mar ker i n P A R T- 2: M A D  ............................................................... 3 2 
6. 3. 3. Taste Assess me nt i n P A R T- 3: r B A/ F E ...................................................... 3 3  
6. 3. 4. Meta b olic Pr ofili n g i n P A R T- 4: M E  .......................................................... 3 3 
6. 3. 5. P K b y Micr osa m pli n g i n P A R T- 2: M A D  ................................................... 3 3 
6. 3. 6. E x pl orat or y A nal ysis fr o m P A R T- 6: S E  .................................................... 3 3 
6. 3. 6. 1. P K of M o xifl o xaci n ................................................................... 3 3  
6. 3. 6. 2. C o nce ntrati o n- Q Tc M o dels ( P A R T- 6: S E o nl y) ....................... 3 4  
6. 3. 6. 3. E val uati o n of Ass u m pti o ns - Li near Mi xe d Effect M o del 
( P A R T- 6: S E o nl y) ............................................................................ 3 5 
6. 3. 6. 4. C o nce ntrati o n- Q Tc Q ua ntile Pl ot ( P A R T - 6: S E o nl y) ............. 3 6 
6. 3. 6. 5. M o del S electi o n a n d E val uati o n ( P A R T - 6: S E o nl y) ............... 3 6 
6. 3. 6. 6. M o del- base d Esti mati o n of Δ Δ Q Tc F at C o nce ntrati o n of 
I nterest ( P A R T- 6: S E o nl y) ............................................................... 3 6 
6. 3. 6. 7. Assa y Se nsiti vit y ( P A R T- 6: S E o nl y) ....................................... 3 7  
6. 4. S u bset A nal yses ....................................................................................................... 3 8  
6. 5. Baseli ne a n d Ot her S u m maries a n d A n al yses ......................................................... 3 8 
6. 5. 1. St u d y C o n d uct a n d Partici pa nt Dis p ositi o n ................................................ 3 8  
6. 5. 2. De m o gra p hic Data ...................................................................................... 3 8  
6. 5. 3. C o nc o mita nt Me dicati o ns a n d N o n dr u g Treat me nts .................................. 3 8  
6. 5. 4. Ot her Scree ni n g Data .................................................................................. 3 8  
6. 6. Safet y S u m maries a n d A nal yses  ............................................................................. 3 8 
6. 6. 1. A d verse E ve nts ........................................................................................... 3 8  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 of 5 5 
6. 6. 2. La b orat or y Data .......................................................................................... 3 8  
6. 6. 3. Vital Si g ns .................................................................................................. 3 9  
6. 6. 4. E C G ............................................................................................................ 3 9  
7. LI S TI N G S O F P A R TI CI P A N T S WI T H A N Y SI N G L E P O S T -D O S E V A L U E 
> 5 0 0 M S E C WI L L A L S O B E P R O D U C E D F O R Q T C F.I N T E RI M A N A L Y S E S .......... 4 0  
7. 1. I ntr o d ucti o n ............................................................................................................. 4 0  
7. 2. I nteri m A nal y ses a n d S u m maries ............................................................................ 4 0 
8. R E F E R E N C E S .................................................................................................................... 4 0  
A P P E N DI C E S  ......................................................................................................................... 4 1 
 
LI S T O F T A B L E S 
Ta ble  1. 
S u m mar y of C ha n ges .................................................................................. 6  
Ta ble 2.  
Treat me nt Se q ue nces i n P A R T - 3: R B A/ F E ............................................. 1 6 
Ta ble 3.  
Treat me nt Se q ue nces i n P A R T -5: D DI  .................................................... 1 7 
Ta ble 4.  
Treat me nt Se q ue nces i n P A R T -6: S E  ....................................................... 1 7 
Ta ble  5. 
Plas ma P F - 0 7 8 1 7 8 8 3 P K Para meters f or P A R T-1: S A D, P A R T - 3: 
R B A/ F E, P A R T- 4: M E a n d P A R T- 6: S E, Mi daz ola m P K 
Para meters i n P A R T - 5: D DI, a n d M o xifl o xaci n P K Para meters i n 
P A R T -6: S E  .............................................................................................. 2 3 
Ta ble  6. 
N o nc o m part me ntal P K Para meters f or P A R T- 2: M A D a n d 
P A R T - 5: D DI (f or P F- 0 7 8 1 7 8 8 3) ............................................................ 2 3 
Ta ble  7. 
P K Para meters t o be S u m marize d Descri pti vel y  ...................................... 3 0 
 
LI S T O F FI G U R E S  
Fi g ure 1. P A R T- 1: S A D  .......................................................................................................... 1 8 
Fi g ure 2. P A R T- 2: M A D  ......................................................................................................... 1 9 
Fi g ure 3. P A R T- 3: R B A/ F E .................................................................................................... 2 0  
Fi g ure 4. P A R T- 4: M E  ............................................................................................................ 2 1 
Fi g ure 5. P A R T- 5: D DI  ........................................................................................................... 2 1 
Fi g ure 6. P A R T- 6: S E  .............................................................................................................. 2 2 
 
A P P E N DI C E S  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 5 of 5 5 
A p pe n di x 2. Cate g orical Classes f or E C G a n d Vital Si g ns of P ote ntial Cli nical 
C o ncer n ..................................................................................................... 5 3  
A p pe n di x 3. List of A b bre viati o ns........................................................................................... 5 4  
A p pe n di x 4. E xa m ple S A S c o de f or Statistical A nal yses ........................................................ 5 5 
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 6 of 5 5 
1.  V E R SI O N  HI S T O R Y  
T a ble 1.  
S u m m ar y of C h a n ges    
V ersi o n / 
D ate 
Ass oci ate d 
Pr ot oc ol 
A me n d me nt  
R ati o n ale  
S pecific C h a n ges  
1 .0  
2 7 Oct  2 0 2 2 
Ori gi nal  
1 4 Se p 2 0 2 2 
 
Pr ot oc ol 
A me n d me nt 1  
2 1 Oct 2 0 2 2 
 
N/ A  
N/ A  
2. 0  
2 4 Ma y 2 0 2 3 
Pr ot oc ol 
A me n d me nt 2  
3 1 Ja n 2 0 2 3 
 
Pr ot oc ol 
A me n d me nt 3  
9 Mar 2 0 2 3 
U p dates base d o n 
S A P te m plate 
u p date, pr ot oc ol 
a me n d me nts, 
A & R pla n re vie w 
a n d Bli n de d Data 
Re vie ws.  
 
Rati o nale: t he pr ot oc ol has bee n 
a me n de d t o  
•  Re m o ve ‘( O pti o nal)’ f or P A R T 
3: R B A/ F E, P A R T 4: M E a n d 
P A R T 5: D DI  
•  A d de d P A R T- 6: S E C o h ort a n d 
O pti o nal C o h ort t o P A R T- 5: 
D DI  
 
T he f oll o wi n g secti o ns were re vise d as 
part of t his rati o nale: 
•  U p date d pr o t oc ol title  
•  Secti o ns 2, 2. 3, 3, 4 a n d 6 – 
u p date d t o matc h pr ot oc ol 
a me n d me nts 
•  Secti o n 2. 2 – a d de d o bjecti ves 
a n d e n d p oi nts f or P A R T- 6 
•  Secti o n 3. 3 – a d de d 
m o xifl o xaci n P K e n d p oi nts; 
u p date d Ta bles 5 a n d 6 f or 
clarit y 
•  Secti o n 3. 6 – a d de d 
micr osa m pli n g P K bl o o d 
sa m ples f or P A R T- 2 
•  Secti o n 6. 3. 1 – m o ve d f o o d 
effect a nal ysis i n P A R T-1 as 
e x pl orat or y e n d p oi nt 
•  Secti o n 6. 3. 2 a d de d a nal ysis f or 
P K bi o mar kers i n P A R T- 2  
•  Secti o n 6. 3. 3 – m o ve d taste 
assess me nt a nal ysis i n P A R T - 3 
as e x pl orat or y e n d p oi nt  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 7 of 5 5 
•  Secti o n 6. 3. 4 –  m o ve d meta b ol ic 
pr ofili n g i n P A R T- 4 as 
e x pl orat or y e n d p oi nt 
•  Secti o n 6. 3. 5 – a d de d a nal ysis 
f or P K micr osa m pli n g i n P A R T-
2 
•  Secti o n 6. 3. 6 – a d de d c Q T 
a nal yses a n d assa y se nsiti vit y 
f or P A R T- 6 
•  Secti o n 8 – a d de d refere nces  
•  A p pe n di x 3 – u p dat e d list of 
a b bre viati o ns 
•  A p pe n di x 4 – a d de d e xa m ple 
S A S c o de f or M M R M of Q Tc F 
 
Rati o nale: C ha n ges t o reflect c urre nt 
S A P te m plate:  
•  A d de d li n ks t o Fi g ures i n Ta ble 
of C o nte nts 
•  Secti o n 2. 2: a d de d “ T y pe” a n d 
“ Esti ma n d” c ol u m n s t o 
o bjecti ve/ e n d p oi nt/esti ma n d 
ta ble 
•  Secti o n 6 . 3 – a d de d secti o ns f or 
e x pl orat or y e n d p oi nts 
 
Rati o nale: C ha n ges t o reflect u p dates 
base d o n o n g oi n g re vie w of ta bles etc : 
•  Secti o n 3. 5. 4 – c ha n ge d 
defi niti o n of  P A R T- 1 baseli ne  
t o matc h t hat use d i n P A R T- 6 
•  Secti o n 6 – clarifie d re p orti n g of 
Ja pa nese a n d C hi nese i n P A R T-
2 a n d P A R T- 5. 
•  Secti o ns 6. 6. 2, 6. 6. 3 a n d 6. 6. 4 – 
a d de d i n di vi d ual partici pa nt 
pr ofiles f or partici pa nts meeti n g 
t he s p o ns or a b n or malit y criteria 
•  Secti o n 6. 6. 3 – re m o ve d 
te m perat ure as o nl y c ollecte d 
d uri n g scree ni n g a n d u n pla n ne d 
visits  
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 8 of 5 5 
2.  I N T R O D U C TI O N 
T he c urre nt st u dy is t he FI H st u dy of P F - 0 7 8 1 7 8 8 3 i n he alt hy a d ult p artici p a nts. It is a 6-
p art st u dy c o m bi ni n g P A R T - 1: S A D, P A R T- 2: M A D, P A R T- 3: R B A/ F E, P A R T-4: M E , 
P A R T- 5: D DI  a n d P A R T- 6: S E. P A R T 1: S A D a n d - 2 : M A D will ev al u ate s afety, 
t oler a bility a n d P K of si n gle a n d m ulti ple esc al ati n g or al d oses of P F 0 7 8 1 7 8 8 3 i n he alt hy 
a d ult p artici p a nts. P A R T 2: M A D  of t he st u dy m ay als o ev al u ate t he s afety, t oler a bility 
a n d P K i n J a p a nese a n d C hi nese p artici p a nts. P A R T- 3: R B A/ F E  will ev al u ate rel ative 
bi o av ail a bility a n d f o o d effect of u p t o 2 ne w P F - 0 7 8 1 7 8 8 3 or al f or m ul ati o ns. P A R T 4 : 
M E  will ev al u ate t he met a b olis m a n d excreti o n of P F - 0 7 8 1 7 8 8 3. P A R T - 5: D DI will 
ev al u ate t he effect of ste a dy -st ate P F 0 7 8 1 7 8 8 3 o n P K of mi d az ol a m i n he alt hy 
p artici p a nts. P A R T - 6: S E  will assess s afety, t oler a bility, a n d P K of P F - 0 7 8 1 7 8 8 3 at S E i n 
he alt hy p artici p a nts . 
Res ults fr o m t his st u dy will i nf or m t he st u dy desi g n of t he P h ase 2/ 3 st u dies i n C O VI D - 1 9 
p atie nts.  
T his statistical a nal ysis pla n ( S A P) pr o vi des t he detaile d met h o d ol o g y f or s u m mar y a n d 
statistical a nal yses of t he data c ollecte d i n St u d y C 5 0 9 1 0 0 1. T his d oc u me nt ma y m o dif y 
t he pla ns o utli ne d i n t he pr ot oc ol; h o we ver, a n y maj or m o dificati o ns of t he pri mar y 
e n d p oi nt defi ni ti o n or its a nal ysis will als o be reflecte d i n a pr ot oc ol a me n d me nt. 
2. 1.  M o dific ati o ns t o t he A n al ysis Pl a n  Descri be d  i n t he Pr ot oc ol 
N ot a p plica ble.  
2. 2.  St u d y O bjecti ves , E n d p oi nts, a n d Esti m a n ds  
T here are n o esti ma n ds f or t his st u d y.  
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 9 of 5 5 
P A R T- 1: S A D 
T y pe  
O bjecti ves  
E n d p oi nts  
Esti m a n d  
 
Pri m ary:  
Pri m ary:  
 
Saf et y  
•  
T o assess t he s afety a n d 
t oler a bility f oll o wi n g si n gle 
asce n di n g d oses of 
P F - 0 7 8 1 7 8 8 3. 
•  
Assess me nt of T E A Es, 
cli nic al l a b or at ory 
a b n or m alities, vit al si g ns, 
a n d 1 2 -le a d E C Gs. 
N/ A  
 
Sec o n d ar y:  
Sec o n d ar y:  
 
P K  
•  
T o assess t he pl as m a P K 
pr ofile of P F - 0 7 8 1 7 8 8 3 
f oll o wi n g si n gle asce n di n g 
d oses of P F - 0 7 8 1 7 8 8 3. 
•  
Pl as m a P K p ar a meters of 
P F - 0 7 8 1 7 8 8 3:  
•  
C m ax , Tm ax , A U Cl ast, 
C m ax ( d n), 
A U C l ast( d n). 
•  
If d at a per mit, 
A U C i nf, A U Ci nf( d n), 
t½ , Vz/ F, a n d C L/ F.  
N/ A  
 
T erti ar y/ E x pl or at or y:  
T erti ar y/ E x pl or at or y:  
 
P K  
•  
T o ex pl ore met a b olites i n 
pl as m a, uri ne, a n d feces, if 
d at a per mit.  
•  
Q u alit ative 
c h ar acteriz ati o n of 
met a b olites of 
P F -0 7 8 1 7 8 8 3 i n p o ole d 
pl as m a, uri ne, a n d feces 
if d at a per mit. 
N/ A  
P K  
•  
T o deter mi ne t he exte nt of 
excreti o n of dr u g  rel ate d 
m ateri al i n uri ne a n d feces 
after a si n gle or al 
a d mi nistr ati o n of P F -
0 7 8 1 7 8 8 3. 
•  
T ot al rec overy of dr u g 
rel ate d m ateri al i n uri ne 
a n d feces  se p ar ately, a n d 
b ot h r o utes c o m bi ne d, 
ex presse d as a perce nt o f 
t ot al d ose a d mi nistere d. 
N/ A  
P K  
•  
T o ev al u ate t he effect of f o o d 
( hi g h f at me al) o n t he 
ex p os ure of P F - 0 7 8 1 7 8 8 3 
f oll o wi n g a si n gle or al d ose of 
P F -0 7 8 1 7 8 8 3, if ev al u ate d 
( O pti o n al). 
•  
T he r ati o of A U C l ast, 
A U C i nf (if d at a per mit) 
a n d C m ax  u n der fe d 
c o n diti o n a n d f aste d 
c o n diti o n. 
N/ A  
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 0 of 5 5 
P A R T- 2: M A D (i ncl u di n g o pti o n al J a p a nese a n d C hi nese c o h ort)  
T y pe  
O bjecti ves  
E n d p oi nts  
Esti m a n d  
 
Pri m ary:  
Pri m ary:  
 
Saf et y  
•  
T o assess t he s afety a n d 
t oler a bility f oll o wi n g m ulti ple 
asce n di n g d oses of P F -
0 7 8 1 7 8 8 3. 
•  
Assess me nt of T E A Es, 
cli nic al l a b or at ory 
a b n or m alities, vit al si g ns, 
a n d 1 2 -le a d E C Gs. 
N/ A  
 
Sec o n d ar y:  
Sec o n d ar y:  
 
P K  
•  
T o assess t he pl as m a P K 
pr ofile of P F -0 7 8 1 7 8 8 3 o n 
D ays 1, 5 a n d 1 0 f oll o wi n g 
m ulti ple asce n di n g d oses of 
P F - 0 7 8 1 7 8 8 3. 
•  
Pl as m a P K p ar a meters of 
P F - 0 7 8 1 7 8 8 3:  
•  
C m ax , Tm ax , A U Ct a u, C1 2, 
C m ax ( d n), A U Ct a u( d n), 
C a v, Rac, Rac, C m ax, 
P T R, C L/ F a n d V z/ F. 
•  
If d at a per mit, t½ . 
N/ A  
P K  
•  
T o assess t he re n al excr eti o n 
of P F -0 7 8 1 7 8 8 3 o n D ay  1 0 
f oll o wi n g m ulti ple asce n di n g 
d oses of P F - 0 7 8 1 7 8 8 3. 
•  
P F -0 7 8 1 7 8 8 3 uri n ary P K 
p ar a meters:  
•  
A e t a u a n d A e t a u%, C L
r. 
N/ A  
 
T erti ar y/ E x pl or at or y:  
T erti ar y/ E x pl or at or y:  
 
P K  
•  
T o ex pl ore P K by 
micr os a m pli n g tec h ni q ue(s), 
if ev al u ate d ( O pti o n al). 
•  
C o nce ntr ati o n of P F -
0 7 8 1 7 8 8 3, if ev al u ate d.  
N/ A  
P K  
•  
T o ex pl ore R B C p artiti o ni n g 
of P F -0 7 8 1 7 8 8 3 ( O pti o n al).  
•  
R ati o of P F -0 7 8 1 7 8 8 3 
c o nce ntr ati o n i n pl as m a t o 
t h at i n bl o o d. 
N/ A  
Bi o mar kers  
•  
T o ex pl ore t he effect of P F -
0 7 8 1 7 8 8 3 o n e n d o ge n o us 
pl as m a bi o m arkers . 
( O pti o n al) 
•  
R ati o of pl as m a 
c o nce ntr ati o ns of e n d o ge n o us 
bi o m arkers o n D ay 1 0 t o 
t h ose bef ore P F- 0 7 8 1 7 8 8 3 
d ose. 
N/ A  
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 1 of 5 5 
P A R T- 3: R B A/ F E   
T y pe  
O bjecti ves  
E n d p oi nts  
Esti m a n d  
 
Pri m ary:  
Pri m ary:  
 
P K  
•  
T o deter mi ne t he or al 
bi o av ail a bility of or al 
f or m ul ati o n(s) of P F-
0 7 8 1 7 8 8 3 rel ative t o 
s us pe nsi o n.  
•  
T h e r ati o of A U C l ast, 
A U C i nf a n d C m ax  of or al 
f or m ul ati o n(s) a n d 
s us p e nsi o n. 
N/ A  
 
Sec o n d ar y:  
Sec o n d ar y:  
 
P K  
•  
T o ev al u ate t he effect of 
f o o d ( hi g h-f at 
hi g h- c al orie me al) o n t he 
ex p os ure of 
P F -0 7 8 1 7 8 8 3 f oll o wi n g a 
si n gle or al d ose of P F-
0 7 8 1 7 8 8 3 t a blet 
f or m ul ati o n(s). 
•  
T he r ati o of A U C l ast, 
A U C i nf a n d C m a x  of t a blet 
f or m ul ati o n u n der fe d 
c o n diti o n a n d f aste d 
c o n diti o n. 
N/ A  
P K  
•  
T o deter mi ne t he 
p h ar m ac oki netics of 
P F -0 7 8 1 7 8 8 3 f oll o wi n g 
or al a d mi nistr ati o n of 
t a blet f or m ul ati o n(s) a n d 
s us pe nsi o n of 
P F - 0 7 8 1 7 8 8 3. 
•  
Pl as m a P K p ar a meters of 
P F -0 7 8 1 7 8 8 3: T m a x,  Cm ax,  
A U C l ast, if d at a per mit 
A U C i nf, t½ , C L/ F, Vz/ F.  
N/ A  
P K  
•  
T o deter mi ne t he s afety 
a n d t oler a bility of P F -
0 7 8 1 7 8 8 3 f oll o wi n g or al 
a d mi nistr ati o n of t a blet 
f or m ul ati o n(s) a n d 
s us pe nsi o n of P F-
0 7 8 1 7 8 8 3. 
•  
Assess me nt of T E A E s, 
cli nic al l a b or at ory 
a b n or m alities, vit al si g ns, 
a n d 1 2 -le a d E C Gs. 
N/ A  
 
T erti ar y/ E x pl or at or y:  
T erti ar y/ E x pl or at or y:  
 
Ot her  
•  
T o ev al u ate t he t aste 
attri b utes of t he 
P F - 0 7 8 1 7 8 8 3 f oll o wi n g 
or al a d mi nistr ati o n of 
or al f or m ul ati o n(s) a n d 
s us pe nsi o n of 
P F - 0 7 8 1 7 8 8 3, if 
ev al u ate d. 
•  
T aste Assess me nt S urvey 
Sc ori n g M etrics: m o ut h 
feel, bitter ness, 
t o n g ue/ m o ut h b ur n, 
t hr o at b ur n, over all 
liki n g. 
N/ A  
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 2 of 5 5 
P A R T- 4: M E  
T y pe  
O bjecti ves  
E n d p oi nts  
Esti m a n d  
 
Pri m ary:  
Pri m ary:  
 
O t h er 
•  
T o deter mi ne t he exte nt 
of excreti o n of dr u g 
rel ate d m ateri al i n 
uri ne a n d feces after a 
si n gle or al 
a d mi nistr ati o n of 
P F - 0 7 8 1 7 8 8 3. 
•  
T ot al rec overy of dr u g 
rel ate d m ateri al i n uri ne 
a n d feces se p ar ately, a n d 
b ot h r o utes c o m bi ne d, 
ex presse d as a perce nt of 
t ot al d ose a d mi nistere d. 
N/ A  
 
Sec o n d ar y:  
Sec o n d ar y:  
 
P K  
•  
T o deter mi ne t he 
p h ar m ac oki netics of 
P F - 0 7 8 1 7 8 8 3 
f oll o wi n g a si n gle or al 
a d mi nistr ati o n of P F -
0 7 8 1 7 8 8 3. 
•  
Pl as m a P K p ar a meters 
of P F -0 7 8 1 7 8 8 3: T m ax , 
C m ax , A U Cl ast, if d at a 
per mit A U C i nf, t½ , C L/ F, 
V z/ F.  
N/ A  
Saf et y  
•  
T o deter mi ne t he s afety 
a n d t oler a bility of 
P F - 0 7 8 1 7 8 8 3 after a 
si n gle or al 
a d mi nistr ati o n of P F -
0 7 8 1 7 8 8 3. 
•  
Assess me nt of T E A E s, 
cli nic al l a b or at ory 
a b n or m alities, vit al 
si g ns, a n d 1 2-le a d E C Gs. 
N/ A  
 
T erti ar y/ E x pl or at or y:  
T erti ar y/ E x pl or at or y:  
 
O t h er 
•  
T o c h ar acterize t he 
met a b olic pr ofile a n d 
i de ntify circ ul ati n g a n d 
excrete d met a b olites 
f oll o wi n g 
a d mi nistr ati o n of a 
si n gle or al d ose of P F-
0 7 8 1 7 8 8 3, if p ossi ble.  
•  
M et a b olic 
pr ofili n g/i de ntific ati o n 
a n d deter mi n ati o n of 
rel ative a b u n d a nce of 
P F -0 7 8 1 7 8 8 3 a n d t he 
met a b olites of 
P F -0 7 8 1 7 8 8 3 i n pl as m a, 
uri ne, a n d feces, if 
p ossi ble. 
N/ A  
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 3 of 5 5 
P A R T- 5: D DI  
T y pe  
O bjecti ves  
E n d p oi nts  
Esti m a n d  
 
Pri m ary O bjective:  
Pri m ary E n d p oi nt:  
 
P K  
•  
T o esti m ate t he effect of 
P F -0 7 8 1 7 8 8 3 o n t he P K  of 
mi d az ol a m. 
•  
Mi d az ol a m pl as m a P K 
p ar a meters: C m ax  a n d 
A U C i nf (if d at a per mit, 
ot her wise A U C l ast) wit h 
P F -0 7 8 1 7 8 8 3 (test) vers us 
wit h o ut P F - 0 7 8 1 7 8 8 3 
(refere nce). 
N/ A  
 
Sec o n d ary O bjective:  
Sec o n d ary E n d p oi nts:  
 
Saf et y  
•  
T o ev al u ate t he s afety a n d 
t oler a bility of 
P F -0 7 8 1 7 8 8 3 i n he alt hy 
p artici p a nts i n t he a bse nce 
a n d prese nce of 
mi d az ol a m.  
•  
Assess me nt of T E A E s, 
cli nic al l a b or at ory 
a b n or m alities, vit al si g ns, 
a n d 1 2- le a d E C Gs. 
N/ A  
P K  
•  
T o ev al u ate t he effects of 
P F -0 7 8 1 7 8 8 3 o n 
a d diti o n al P K p ar a meters 
of mi d az ol a m i n he alt hy 
p artici p a nts. 
•  
Mi d az ol a m pl as m a P K 
p ar a meters: T m a x , A U Cl ast, 
a n d if d at a per mit t½ , 
C L/ F, a n d V z/ F f or 
mi d az ol a m wit h a n d 
wit h o ut c o a d mi nistr ati o n 
of P F -0 7 8 1 7 8 8 3.  
N/ A  
 
T erti ary/ E x pl or at ory 
O bjectives:  
T erti ary/ E x pl or at ory 
E n d p oi nts:  
 
P K  
•  
T o assess t he pl as m a P K 
pr ofile of P F -0 7 8 1 7 8 8 3 o n 
D ays 1, 5 ( o pti o n al) a n d 
1 0 f oll o wi n g m ulti ple 
asce n di n g d oses of P F -
0 7 8 1 7 8 8 3. 
•  
Pl as m a P K p ar a meters of 
P F - 0 7 8 1 7 8 8 3:  
•  
C m ax , Tm ax , A U Ct a u, 
C 1 2, Cm ax ( d n), 
A U C t a u( d n), Ca v, Rac, 
R ac, C m ax, P T R, C L/ F 
a n d V z/ F. 
•  
If d at a per mit, t½ . 
N/ A  
P K  
•  
T o assess t he pl as m a P K 
pr ofile of P F -0 7 8 1 7 8 8 3 o n 
D ays 1, 5 ( o pti o n al) a n d 
1 0 f oll o wi n g m ulti ple 
asce n di n g d oses of P F -
0 7 8 1 7 8 8 3 i n C hi nese a n d 
J a p a nese p artici p a nts 
( O pti o n al). 
•  
Pl as m a P K p ar a meters of 
P F - 0 7 8 1 7 8 8 3:  
•  
C m ax , Tm ax , A U Ct a u, 
C 1 2, Cm ax ( d n), 
A U C t a u( d n), Ca v, Rac, 
R ac, C m ax, P T R, C L/ F 
a n d V z/ F. 
•  
If d at a per mit, t½ . 
N/ A  
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 4 of 5 5 
P A R T- 6: S E   
T y pe  
O bjecti ves  
E n d p oi nts  
Esti m a n d  
 
Pri m ary O bjective:  
Pri m ary E n d p oi nt:  
 
Saf et y  
•  
T o assess t he s afety a n d 
t oler a bility of a S E of P F -
0 7 8 1 7 8 8 3 a d mi nistere d 
as s plit d osi n g.  
•  
Assess me nt of T E A Es, 
cli nic al l a b or at ory  
a b n or m alities, vit al si g ns, 
a n d 1 2- le a d E C Gs. 
N/ A  
 
Sec o n d ary O bjective:  
Sec o n d ary E n d p oi nts:  
 
P K  
•  
T o assess t he pl as m a P K 
of P F -0 7 8 1 7 8 8 3 at a n  S E 
of P F - 0 7 8 1 7 8 8 3 
a d mi nistere d as s plit 
d osi n g. 
•  
Pl as m a P K p ar a meters of 
P F - 0 7 8 1 7 8 8 3: 
•  
C m ax , Tm ax , A U Cl ast 
•  
If d at a per mit, A U Ci nf, 
t½ . 
N/ A  
 
T erti ary/ E x pl or at ory 
O bjectives:  
T erti ary/ E x pl or at ory 
E n d p oi nts:  
 
P K  
•  
T o assess t he pl as m a P K 
of m oxifl ox aci n  
•  
Pl as m a m oxifl ox aci n 
p ar a meters C m a x , Tm a x  
a n d A U C l ast. 
N/ A  
Ot her  
•  
T o deter mi ne ass ay 
se nsitivity by c o m p ari n g 
t he effect of m oxifl ox aci n 
4 0 0 m g o n Q Tc F i nterv al 
wit h pl ace b o at hist oric al 
m oxifl ox aci n T m a x  of 3  
h o urs. 
•  
Ti me m atc he d me a n 
differe nces i n Q Tc F  
bet wee n m oxifl ox aci n 
a n d pl ace b o at t he  
hist oric al m oxifl ox aci n 
T m ax  of 3 h o urs.  
N/ A  
Ot her  
•  
T o deter mi ne ass ay 
se nsitivity by ex p os ur e-
res p o nse a n alysis of 
m oxifl ox aci n  
•  
B aseli ne c orrecte d 
Q Tc F  
N/ A  
Ot her  
•  
T o deter mi ne ex p os ure 
res p o nse a n alysis of P F -
0 7 8 1 7 8 8 3 
•  
B aseli ne c orrecte d 
Q Tc F  
N/ A  
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 5 of 5 5 
2. 3.  St u d y Desi g n  
2. 3. 1.  O ver all Desi g n  
T his 6 - p art, P h ase 1, FI H st u dy will c o m bi ne P A R T- 1: S A D, P A R T- 2: M A D (i ncl u di n g 
o pti o n al J a p a nese a n d C hi nese C o h orts), P A R T- 3: R B A/ F E, P A R T - 4: M E, P A R T-5: D DI  
a n d P A R T- 6: S E. P A R T- 1 a n d P A R T- 2 are a r a n d o mize d, d o u ble- bli n d, s p o ns or - o pe n, 
pl ace b o- c o ntr olle d st u dy t o ev al u ate s afety,  t oler ability, a n d P K of si n gle a n d m ulti ple 
esc al ati n g or al d oses of P F- 0 7 8 1 7 8 8 3 i n he alt hy  a d ult p artici p a nts, res pectively. P A R T - 2 
of t he st u dy m ay als o ev al u ate t he s afety,  t oler a bility, a n d P K i n J a p a nese a n d C hi nese 
p artici p a nts. P A R T - 3 is a r a n d o mize d, o pe n-l a bel, cr oss- over, st u dy t o ev al u ate R B A a n d 
F E of 2 ne w P F - 0 7 8 1 7 8 8 3 or al f or m ul ati o ns. P A R T - 4 is a n o pe n-l a bel, n o n-r a n d o mize d, 
si n gle peri o d t o ev al u ate t he M E of P F- 0 7 8 1 7 8 8 3. P A R T- 5 is a n o pe n-l a bel, r a n d o mize d, 
cr oss-over st u dy t o ev al u ate t he effect  of ste a dy-st ate P F- 0 7 8 1 7 8 8 3 o n P K of mi d az ol a m i n 
he alt hy a d ult p artici p a nts. P A R T - 6: S E is a s p o ns or- o pe n, r a n d o mize d, 3-tre at me nt, 3-
peri o d, 6- se q ue nce, cr oss- over, pl ace b o-a n d  p ositive -c o ntr olle d st u dy t o ev al u ate s afety, 
t oler a bility, a n d P K at S E i n he alt hy p artici p a nts. 
2. 3. 2.  P A R T - 1: S A D 
S A D will i ncl u de 2 i nterle avi n g c o h orts wit h a t ot al of a p pr oxi m ately 1 6 p artici p a nts 
pl a n ne d ( a p pr oxi m ately 8 p artici p a nts i n e ac h c o h ort – 6 active: 2 pl ace b o), wit h 3- peri o d, 
cr oss- over i n e ac h c o h ort. Peri o d 3 is a n o pti o n al peri o d w hic h m ay be use d t o f urt her 
ex pl ore P K at a d diti o n al d oses or assess f o o d effect ( hi g h-f at hi g h-c al orie me al), b ase d o n 
e mer gi n g s afety, t oler a bility a n d P K assess me nts.  T here will be a w as h o ut i nterv al of ≥5 
d ays bet wee n d osi n g t o a give n p artici p a nt. 
2. 3. 3.  P A R T - 2: M A D 
T he first M A D c o h ort m ay st art after a t ot al d aily d ose, w hic h pr ovi des c o m p ar a ble or 
hi g her t ot al d aily ex p os ure ( 2 4 h) i n S A D t o t he pr ojecte d t ot al d aily ste a dy -st ate ex p os ure 
( over 2 4 h) at t he st arti n g d ose i n M A D, is f o u n d s afe a n d well t oler ate d i n t he P A R T - 1 of 
t he st u dy. T he pr o p ose d M A D st u dy desi g n will be p ar allel c o h orts, wit h 1 0 d ays of d osi n g. 
P A R T- 2  will c o nsist of a p pr oxi m ately 2 t o 6 c o h orts i ncl u di n g u p t o 4 o pti o n al c o h orts 
( C o h orts 5, 6, 7 a n d 8) wit h a p pr oxi m ately 6 p artici p a nts i n e ac h c o h ort ( 4 active: 2 
pl ace b o). C o h orts 7 a n d 8 are o pti o n al J a p a nese a n d C hi nese p artici p a nts, res pectively. 
D ose esc al ati o n t o s u bse q ue nt d ose levels i n M A D c o h orts will be b ase d o n a mi ni m u m of 6 
d ays s afety d at a a n d P K over a p p r oxi m ately ≥6 h o urs o n D ay 5 i n a mi ni m u m of 4 
p artici p a nts ( 3 active a n d 1 pl ace b o) at previ o us d ose levels. 
2. 3. 4.  P A R T - 3: R B A/ F E  
T his c o h ort will be a n o pe n-l a bel, r a n d o mize d, 4- peri o d, 6-se q ue nce cr oss- over si n gle d ose 
c o h ort ev al u ati n g t he R B A of 2 ne w P F - 0 7 8 1 7 8 8 3 or al f or m ul ati o n(s) c o m p are d t o P F-
0 7 8 1 7 8 8 3 or al s us pe nsi o n a n d t o ev al u ate t he effect of f o o d o n t he bi o av ail a bility of t he 
P F - 0 7 8 1 7 8 8 3 or al f or m ul ati o n(s) i n he alt hy a d ult p artici p a nts. A n ex pl or at ory assess me nt 
of t he t aste m ay be c o n d ucte d.  A p pr oxi m ately 1 2 p artici p a nts m ay be  e nr olle d i n P A R T- 3 of 
t he st u dy wit h a p pr oxi m ately e q u al n u m ber of p artici p a nts r a n d o mize d t o 1 of 6 se q ue nces. 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 6 of 5 5 
I n t his p art, t here will be a w as h o ut i nterv al of at le ast 3 d ays bet wee n d osi n g t o a give n 
p artici p a nt i n  e ac h peri o d. 
 
T a ble 2. 
Tre at me nt Se q ue nces i n P A R T - 3: R B A/ F E 
Se q ue nce  
P eri o d 1  
P eri o d 2  
P eri o d 3  
P eri o d 4  
1  
A  
B  
C  
D  
2  
B  
C  
A  
D  
3  
C  
A  
B  
D  
4   
B  
A  
C  
E  
5   
A  
C  
B  
E  
6  
C  
B  
A  
E  
Tr eat me nt A = P F -0 7 8 1 7 8 8 3 6 0 0 m g or al s us pe nsi o n S D Faste d; 
Tr eat me nt B = P F -0 7 8 1 7 8 8 3 6 0 0 m g F or m ulati o n 1
Faste d  
Tr eat me nt C = P F -0 7 8 1 7 8 8 3 6 0 0 m g F or m ulati o n 2
Faste d  
Tr eat me nt D = P F -0 7 8 1 7 8 8 3 6 0 0 m g F or m ulati o n 1
 Fe d ( hi g h-f at meal) 
Tr eat me nt E = P F -0 7 8 1 7 8 8 3 6 0 0 m g F or m ulati o n 2
Fe d ( hi g h -f at meal) 
2. 3. 5.  P A R T - 4: M E 
T his p art will i ncl u de a si n gle c o h ort of a p pr oxi m ately 6 m ale p artici p a nts. T he d ose of t his 
c o h ort will be deci de d b ase d o n t he e mer gi n g P K a n d s afety d at a.  T he selecte d d ose will  
n ot excee dt he hi g hest d ose dee me d s afe i n P A R T - 1. E ac h p artici p a nt will receive a si n gle 
d ose of P F- 0 7 8 1 7 8 8 3 at 0 hr o n D ay 1 after at le ast 1 0 hr of f asti n g. T he p artici p a nts will 
be disc h ar ge d o n D ay 1 1. 
2. 3. 6.  P A R T -5: D DI  
T his p art m ay c o nsist of u p t o 2 c o h orts ( C o h ort 1 1 a n d o pti o n al C o h ort 1 2). B ase d o n t he 
d at a fr o m t he C o h ort 1 1, a n o pti o n al C o h ort 1 2 m ay be i niti ate d at a d ose l o wer t h a n t he 
6 0 0 m g BI D. B ot h  c o h orts will h ave 2 tre at me nts, 2 se q ue nces, a n d 2 peri o ds wit h a cr oss-
over desi g n t o ev al u ate t he  effect of ste a dy-st ate P F- 0 7 8 1 7 8 8 3 o n t he P K of mi d az ol a m i n 
he alt hy a d ult p artici p a nts. T he d ose of P F - 0 7 8 1 7 8 8 3 i n C o h ort 1 1 is 6 0 0 m g BI D a n d t he 
d ose of C o h ort 1 2 will be deci de d b ase d o n t he e mer gi n g P K d at a fr o m C o h ort 1 1. E ac h 
e nr olle d  p artici p a nt will be r a n d o mly assi g ne d t o 1 of 2 se q ue nces t o receive 2 tre at me nts 
i n 2 peri o ds. T h e 2 tre at me nts  i n t his p art will be: si n gle or al d ose of 5 m g mi d az ol a m 
al o ne ( Tre at me nt A) a n d m ulti ple or al d oses of P F- 0 7 8 1 7 8 8 3 i n c o m bi n ati o n wit h a si n gle 
or al d ose of 5 m g mi d az ol a m ( Tre at me nt B). A t ot al of a p pr oxi m ately 1 4 he alt hy 
p artici p a nts will be e nr olle d i n  e ac h c o h ort t o  e ns ure at le ast 1 2 p artici p a nts will c o m plete 
t h at c o h ort. 
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 1 7 of 5 5 
T a ble 3.  
Tre at m e nt Se q ue nces i n P A R T -5: D DI  
 
P eri o d 1  
P eri o d 2  
Se q ue nce 1 ( n = 7)  
Tre at me nt A  
Tre at me nt B  or  
Tre at me nt C  
Se q ue nce 2 ( n = 7)  
Tre at me nt B  or  
Tre at me nt C  
Tre at me nt A  
•  
Tre at me nt A: Si n gle or al d ose of 5 m g mi d az ol a m wit h at le ast 2 -d ay w as h o ut ( Tre at me nt A peri o d 
d ur ati o n: D ay 1 t o D ay 3).  
•  
Tre at me nt B: P F -0 7 8 1 7 8 8 3 a d mi nistere d or ally f or 1 0 d ays: D ay 1 m or ni n g t o D ay 1 0 m or ni n g. O n 
D ay 1 0 m or ni n g, p artici p a nts will receive a si n gle or al d ose of 5 m g mi d az ol a m a d mi nistere d wit h 
P F -0 7 8 1 7 8 8 3, f oll o we d by a 7 -d ay w as h o ut ( Tre at me nt B peri o d d ur ati o n: D ay 1 t o D ay 1 7).  
•  
Tre at me nt C: P F -0 7 8 1 7 8 8 3 a d mi nistere d or ally f or 1 0 d ays: D ay 1 m or ni n g t o D ay 1 0 m or ni n g. O n 
D ay 5 m or ni n g a n d D ay 1 0 m or ni n g, p artici p a nts will receive a si n gle or al d ose of 5 m g mi d az ol a m 
a d mi nistere d wit h P F -0 7 8 1 7 8 8 3. A 7 -d ay w as h o ut t o f oll o w after l ast P F -0 7 8 1 7 8 8 3 a d mi nistr ati o n 
( Tre at me nt C peri o d d ur ati o n: D ay 1 t o D ay 1 7). 
 
2. 3. 7.  P A R T - 6: S E 
T his is a si n gle -d ose, r a n d o mize d, 3 -tre at me nt, 3-peri o d, cr oss -over, 6 -se q ue nce, 
s p o ns or o pe n, pl ace b o- a n d p ositive-c o ntr olle d st u dy t o be c o n d ucte d i n a p pr oxi m ately 2 4 
a d ult he alt hy p artici p a nts. E ac h p artici p a nt will be r a n d o mly assi g ne d t o o ne of t he  
re at me nt se q ue nces s h o w n i n T a ble 4. T he p artici p a nts r a n d o mize d t o tre at me nt will 
receive 6 0 0 0 m g as 2 s plit d oses of P F- 0 7 8 1 7 8 8 3 3 0 0 0 m g a d mi nistere d at 0 a n d 1 h. T he 
p artici p a nt r a n d o mize d t o pl ace b o will receive pl ace b o at 0 a n d 1 h. T he p artici p a nts 
r a n d o mize d t o m oxifl ox aci n will receive m oxifl ox aci n 4 0 0 m g a n d pl ace b o at 0 a n d 1 h, 
res pectively. Tre at me nt assi g n me nts t o P F - 0 7 8 1 7 8 8 3 a n d pl ace b o will be bli n de d t o t he 
p artici p a nts, i nvesti g at or a n d C R U st aff (exce pt p h ar m acy st aff) b ut o pe n t o t he s p o ns or. 
A d mi nistr ati o n  of m oxifl ox aci n a n d pl ace b o i n p artici p a nts r a n d o mize d t o m oxifl ox aci n 
tre at me nt will be o pe n l a bel. E ac h peri o d will be se p ar ate d by at le ast 7 d ays of w as h- o ut 
i nterv al. Se nti nel d osi n g will be i m ple me nte d i n t his c o h ort.  
T a ble 4. 
Tre at me nt Se q ue nces i n P A R T - 6: S E 
 
 
P eri o d 1  
P eri o d 2  
P eri o d 3  
Se q ue nce 1 ( n = 4 ) 
A  
B  
C  
Se q ue nce 2 ( n = 4 ) 
B  
C  
A  
Se q ue nce 3  ( n =4 ) 
C  
A  
B  
Se q ue nce 4  ( n =4 ) 
B  
A  
C  
Se q ue nce 5  ( n =4 ) 
A 
C 
B  
Se q ue nce 6  ( n =4 ) 
C 
B 
A  
Tre at me nt A: P F -0 7 8 1 7 8 8 3 6 0 0 0 m g or al s us pe nsi o n a d mi nistere d as 2 s plit -d oses of 3 0 0 0 m g at 0 a n d 1 h i n 
f aste d st ate. 
Tre at me nt B: Pl ace b o or al s us pe nsi o n.  
Tre at me nt C: M oxifl ox aci n 4 0 0 m g S D at 0 h a n d pl ace b o at 1 h i n f aste d st ate.  
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Protocol C5091001 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 18 of 55
2.3.8. Number of Participants
A total of up to 122 participants (16 in PART-1: SAD, up to 36 [with 2 cohorts and 4 
optional cohorts] in PART-2: MAD, 12 in PART-3: RBA/FE cohort, 6 in PART-4: ME, up 
to 28 [with 2 cohorts of 14 each] in PART-5: DDI and 24 in PART-6: SE) are planned to
be enrolled in this study.
Figure 1. PART-1: SAD 
090177e19d8c50d2\Final\Final On: 24-May-2023 13:18 (GMT)


Protocol C5091001 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 19 of 55
Figure 2. PART-2: MAD 
090177e19d8c50d2\Final\Final On: 24-May-2023 13:18 (GMT)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 0 of 5 5 
Fi g ure 3 . P A R T- 3: R B A/ F E   
C o h ort 9: 
 
 
F or m ul ati o n 1:  
 
F or m ul ati o n 2:  
 
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI
C CI


Protocol C5091001 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 21 of 55
Figure 4. PART-4: ME
Cohort 10:
Figure 5. PART-5: DDI
Cohort 11:
Cohort 12 (Optional):
Washout duration may be modified based on emerging data.
090177e19d8c50d2\Final\Final On: 24-May-2023 13:18 (GMT)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 2 of 5 5 
Fi g ure 6 . P A R T- 6: S E  
C o h ort 1 3: 
 
3.  E N D P OI N T S  A N D B A S E LI N E V A RI A B L E S:  D E FI NI TI O N S A N D 
C O N V E N TI O N S  
3. 1.  Pri m ar y E n d p oi nt(s) 
As liste d i n Secti o n 2. 2  t he pri mar y e n d p oi nts i n P A R T - 1, P A R T - 2 a n d P A R T - 6 are 
relate d t o safet y/t olera bilit y a n d are descri be d i n Secti o n 3. 5 .  
T he pri mar y e n d p oi nts i n P A R T - 3 are t he P F - 0 7 8 1 7 8 8 3 plas ma P K e n d p oi nts w hic h are 
descri be d i n Secti o n 3. 3 .  
T he pri mar y e n d p oi nts i n P A R T - 4 are t otal  rec o ver y of dr u g-relate d material i n uri ne, 
feces a n d b ot h r o utes c o m bi ne d, deter mi ne d base d o n t otal a d mi nistere d d ose. Perce nt 
rec o ver y of dr u g-relate d material i n uri ne a n d feces will be deter mi ne d base d o n t otal 
a d mi nistere d d ose. 
T he pri mar y e n d p oi nts i n P A R T - 5 are Mi daz ola m plas ma P K e n d p oi nts: C ma x  a n d A U C i nf 
(if data per mit, ot her wise A U Clast) wit h P F- 0 7 8 1 7 8 8 3 (test) vers us wit h o ut P F - 0 7 8 1 7 8 8 3 
(refere nce). 
3. 2.  Sec o n d ar y E n d p oi nt(s)  
T he sec o n dar y e n d p oi nts i n P A R T- 1 , P A R T - 2 a n d P A R T - 6 are relate d t o P K are 
descri be d i n Secti o n 3. 3 . T he sec o n dar y e n d p oi nts i n P A R T - 3, P A R T - 4 a n d P A R T - 5 are 
relate d t o P K descri be d i n Secti o n 3. 3  a n d safet y/t olera bilit y are descri be d i n Secti o n 3. 5 . 
3. 3.  Ot her E n d p oi nt(s)  
3. 3. 1.  P h ar m ac o ki netic ( P K) E n d p oi nts  
Bl o o d a n d uri ne sa m ples f or t he P K a nal ysis of P F - 0 7 8 1 7 8 8 3/ mi daz ola m/ m o xifl o xaci n will 
be ta ke n acc or di n g t o t he S o A gi ve n i n t he pr ot oc ol.  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 3 of 5 5 
T he P K para meters of P F - 0 7 8 1 7 8 8 3, mi daz ola m ( P A R T - 5) a n d m o xifl o xaci n (P A R T - 6) 
will  be deri ve d (if data per mit) fr o m t he c o nce ntrati o n-ti me data usi n g sta n dar d 
n o nc o m part me ntal met h o ds defi ne d i n Ta ble  5 (si n gle oral d ose) a n d Ta ble 6 ( m ulti ple oral 
d oses). Uri ne P F- 0 7 8 1 7 8 8 3 P K para meters are descri be d i n . Act ual P K sa m pli n g ti mes 
will be use d i n t he deri vati o n of P K para meters. I n t he case t hat act ual P K sa m pli n g ti mes 
are n ot a vaila ble, n o mi nal P K sa m pli n g ti me will be u se d i n t he deri vati o n of P K 
para meters.  
 
T a ble 5.  
Pl as m a P F- 0 7 8 1 7 8 8 3 P K P ar a meters f or P A R T- 1: S A D, P A R T - 3: R B A/ F E, P A R T-
4: M E a n d P A R T- 6: S E, Mi d az ol a m P K P ar a meters i n P A R T - 5: D DI, a n d 
M o xifl o x aci n P K P ar a meters i n P A R T - 6: S E  
P ar a m et er  
P art of t he St u d y  
A n al ysis Sc ale  
P F -0 7 8 1 7 8 8 3 / 
Mi d az ol a m/ M o xifl o x aci n  
A U C last† a 
1, 3, 4, 5, 6  
l n 
D, A  
A U C i nf*  ¶ 
1, 3, 4, 5, 6  
l n 
D, A  
C m a x a 
1, 3, 4, 5, 6  
l n 
D, A  
 
T ma x a 
 
1, 3, 4, 5, 6  
R  
D  
t½ *  ¶ 
1, 3, 4, 5, 6  
R  
D  
C L/ F * 
1, 3, 4, 5, 6  
l n 
D  
V z/ F*   
1, 3, 4, 5, 6  
l n 
D  
A U C last( d n) ‡  
1  
l n 
D  
A U C i nf( d n)* ‡  
1  
l n 
D  
C m a x ( d n) ‡  
1  
l n 
D  
Ke y:  
D = dis pla ye d wit h descri pti ve statistics,  
 
l n = nat ur al-l o g tr a nsf or me d, R =r a w ( u ntr a nsf or me d), A =a nal yse d 
* =if data per mits, d n = n or malize d t o a 1 m g P F -0 7 8 1 7 8 8 3 d ose,  
† = I n P A R T-3, pr e -d ose ( 0 h) sa m ple fr o m Peri o ds 2 a n d 3 will als o be c o nsi der e d as 4 8 h P K sa m ple f or Peri o ds 
1 a n d 2, r es pecti vel y,  
‡ = N ot r e q uir e d e xce pt P A R T - 1, 
a O nl y selecte d P K par a meters t o be calc ulate d f or m o xifl o xaci n i n P A R T - 6 
 
 
I n P A R T - 3, pre-d ose ( 0 h) sa m ple fr o m Peri o ds 2 a n d 3 will als o be c o nsi dere d as 4 8 h P K 
sa m ple f or Peri o ds 1 a n d 2, res pecti vel y.  I n P A R T-5, Se q ue nce 1, Da y 1, 0 h sa m ple of 
mi daz ola m i n Peri o d 2 will be c o nsi dere d as 4 8 h P K f or Peri o d 1. 
T last will als o be pr o vi de d  as a s u p p ort para meter f or A U Clast. Tlast val ues will o nl y be liste d 
a n d n ot s u m marize d. 
T a ble 6.  
N o nc o m p art me nt al P K P ar a meters f or P A R T- 2: M A D a n d P A R T - 5: D DI  (f or P F -
0 7 8 1 7 8 8 3) 
P ar a m et er  
D a y(s) a 
A n al ysis Sc ale  
P F -0 7 8 1 7 8 8 3  
Pl as m a  
A U C τ 
1, 5, 1 0  
l n 
D  
C m a x  
1, 5, 1 0  
l n 
D  
T ma x  
1, 5, 1 0  
R  
D  
C 1 2 
5, 1 0  
l n 
D  
P T R  
5, 1 0  
l n 
D  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 4 of 5 5 
T a ble 6.  
N o nc o m p art me nt al P K P ar a meters f or P A R T- 2: M A D a n d P A R T - 5: D DI  (f or P F -
0 7 8 1 7 8 8 3) 
P ar a m et er  
D a y(s) a 
A n al ysis Sc ale  
P F -0 7 8 1 7 8 8 3  
R a c 
5, 1 0  
l n 
D  
R a c, C m a x 
5, 1 0  
l n 
D  
C L/ F  
5, 1 0  
l n 
D  
t½ * 
1 0  
R  
D  
V z/ F* 
1 0  
l n 
D  
A U C τ( d n) 
1, 5, 1 0  
l n 
D  
C m a x ( d n) 
1, 5, 1 0  
l n 
D   
C a v 
1, 5, 1 0  
l n 
D  
Uri ne b  
Ae τ 
1 0  
l n 
D  
Ae τ%  
1 0  
l n 
D  
C L r 
1 0  
l n 
D  
Ke y:  
D = dis pla ye d wit h descri pti ve statistics,  
 
l n = nat ur al-l o g tr a nsf or me d, R =r a w ( u ntr a nsf or me d),  
* =if data per mits, d n = n or malize d t o a 1 m g P F -0 7 8 1 7 8 8 3 d ose.  
a. Da y 5 o pti o nal f or P A R T - 5. 
b. Uri ne par a meters ar e n ot a p plica ble f or P A R T -5.  
 
3. 4.  B aseli ne V ari a bles  
Baseli ne f or la b orat or y data, vital si g ns a n d E C G are defi ne d i n Secti o ns 3. 5. 2 , 3. 5. 3  a n d 
3. 5. 4  res pecti vel y. 
3. 5.  S afet y E n d p oi nts 
3. 5. 1.  A d verse E ve nts 
A n a d verse e ve nt is c o nsi dere d a Treat me nt -E mer ge nt A d verse E ve nt ( T E A E) if t he e ve nt 
starte d d uri n g t he effecti ve d urati o n of treat me nt. All e ve nts t hat start o n or after t he first 
d osi n g da y a n d ti me /start ti me, if c ollecte d, b ut bef ore t he e n d of t he st u d y will be fla g ge d 
as T E A Es. T he al g orit h m will n ot c o nsi der a n y e ve nts t hat starte d pri or t o t he first d ose 
date.  
3. 5. 2.  L a b or at or y D at a 
Safet y la b orat or y tests will be perf or me d as descri be d i n t he pr ot oc ol.  
F or P A R T - 1, P A R T - 3, P A R T - 5 a n d P A R T - 6, baseli ne will be t he last pre- d ose 
meas ure me nt pri or t o a d mi nistrati o n of P F - 0 7 8 1 7 8 8 3, place b o, mi daz ola m or m o xifl o xaci n 
(as a p plica ble) i n eac h st u d y peri o d. F or P A R T - 2, baseli ne will be t he last pre- d ose 
meas ure me nt. F or P A R T - 4, baseli ne will be t he last pre- d ose meas ure me nt pri or t o 
a d mi nistrati o n of P F - 0 7 8 1 7 8 8 3.  
T o deter mi ne if t here are a n y cli nicall y si g nifica nt la b orat or y a b n or malities, t he 
he mat ol o gical, cli nical  c he mistr y (ser u m) a n d uri nal ysis safet y tests will be assesse d 
a gai nst t he criteria s pecifie d i n t he s p o ns or re p orti n g sta n dar ds. T he assess me nt will ta ke 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 5 of 5 5 
i nt o acc o u nt w het her eac h partici pa nt’s baseli ne test res ult is wit hi n or o utsi de t he 
la b orat or y refere nce ra n ge f or t he partic ular  la b orat or y para meter. 
F or P A R T - 1, P A R T - 2, P A R T - 5 a n d P A R T - 6 cha n ge fr o m baseli ne a n d perce nt c ha n ge 
fr o m baseli ne will be calc ulate d f or eac h p ost-baseli ne ti me p oi nt. T his will be f or all 
he mat ol o g y  a n d c he mistr y  safet y la bs will be i ncl u de d pl us a P T T, P T, I N R, A m ylase a n d 
Li pase.  
3. 5. 3.  Vit al Si g ns 
Si n gle s u pi ne bl o o d press ure, res pirat or y rate a n d p ulse meas ure me nts will be ta ke n at 
ti mes detaile d i n t he S o A  gi ve n i n t he pr ot oc ol.  
F or P A R T - 1, P A R T - 3 P A R T - 5 a n d P A R T - 6, baseli ne will be defi ne d as t he last pre - d ose 
meas ure me nt  i m me diatel y pri or t o first a d mi nistrati o n of st u d y i nter ve nti o n  i n eac h st u d y 
peri o d.  U n pla n ne d meas ure me nts will be use d w here a p plica ble.  
F or P A R T - 2, baseli ne will be t he last pre-d ose meas ure me nt.  
F or P A R T - 4 baseli ne will be t he last pre -d ose meas ure me nt pri or t o a d mi nistrati o n of P F -
0 7 8 1 7 8 8 3. 
T he f oll o wi n g vital si g ns e n d p oi nts will be deter mi ne d:  
 
•  C ha n ge fr o m baseli ne i n s u pi ne s yst olic a n d diast olic bl o o d press ure, p ulse rate a n d 
res pirat or y rate. 
 
•  T he ma xi m u m decrease fr o m baseli ne o ver all meas ure me nts ta ke n p ost - d ose f or 
s u pi ne s yst olic a n d diast olic bl o o d press ures a n d res pirat or y rate.  
 
•  T he ma xi m u m i ncrease fr o m baseli ne o ver all meas ure me nt s ta ke n p ost- d ose f or 
s u pi ne p ulse rate.  
 
T he ma xi m u m i ncrease fr o m baseli ne will be calc ulate d b y first s u btracti n g t he baseli ne 
val ue fr o m eac h p ost- d ose meas ure me nt t o gi ve t he c ha n ge fr o m baseli ne. T he ma xi m u m 
of t hese val ues o ver t he res pecti ve peri o d will t he n be selecte d, e xce pt i n t he case  w here a 
partici pa nt d oes n ot s h o w a n i ncrease. I n s uc h a n i nsta nce, t he mi ni m u m decrease s h o ul d be 
ta ke n.  
Si milarl y, t he ma xi m u m decrease fr o m baseli ne will be deter mi ne d b y selecti n g t he 
mi ni m u m val ue of t he c ha n ges fr o m baseli ne.  I n cases w here a part ici pa nt d oes n ot s h o w a 
decrease, t he mi ni m u m i ncrease s h o ul d be ta ke n.  
If 3 of m ore partici pa nts ha ve a n u n pla n ne d meas ure me nts at t he sa me ti mep oi nt t hese ma y 
be s u m marize d  i n a d diti o n t o t he pla n ne d ti me p oi nts. 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 6 of 5 5 
3. 5. 4.  E C G  
A 1 2 -lea d E C G will be o btai ne d o n all partici pa nts at scree ni n g. 1 2- lea d E C Gs will be 
rec or de d o n all partici pa nts at ti mes detaile d i n t he S o A  gi ve n i n t he pr ot oc ol. Tri plicate 
meas ure me nts will be perf or me d i n P A R T - 1, P A R T - 2 a n d P A R T - 6, a n d si n gle 
meas ure me nts i n P A R T - 3, P A R T - 4 a n d P A R T - 5. T he Q T, heart rate, Q Tc F, P R a n d Q R S 
will be rec or de d at eac h assess me nt ti me. T he a vera ge of t he tri plicate rea di n gs c ollecte d 
( w here a p plica ble) at eac h assess me nt ti me will be calc ulate d f or eac h E CG para meter.  
F or P A R T - 1 a n d P A R T - 6 baseli ne will be defi ne d as t he a vera ge of t he 
tri plicate meas ure me nts  at 3 ti me p oi nts (- 1 h o ur, - 0. 5 h o ur, a n d 0 h o urs) pri or t o 
a d mi nistrati o n of st u d y treat me nt i n eac h st u d y peri o d.  
F or P A R T - 2, baseli ne will be defi ne d as t he a vera ge of t he tri plicate meas ure me nts pri or t o 
a d mi nistrati o n of st u d y treat me nt.  
F or P A R T - 3 a n d P A R T - 5, baseli ne will be defi ne d t he last meas ure me nt pri or t o 
a d mi nistrati o n of st u d y treat me nt i n eac h st u d y peri o d.  
F or  P A R T - 4, baseli ne will be defi ne d as t he last meas ure me nt pri or t o a d mi nistrati o n of 
P F - 0 7 8 1 7 8 8 3. 
T he f oll o wi n g E C G e n d p oi nts will be deter mi ne d: 
•  C ha n ge fr o m baseli ne i n Q T i nter val, heart rate, Q Tc F i nter val, P R i nter val, a n d 
Q R S c o m ple x . 
  
•  T he ma xi m u m a b s ol ute val ue ( p ost- d ose) will be calc ulate d f or Q Tc F, P R a n d Q R S.  
 
•  T he ma xi m u m i ncrease fr o m baseli ne o ver all meas ure me nts ta ke n p ost -d ose will 
be calc ulate d f or Q Tc F.  
T he ma xi m u m i ncrease fr o m baseli ne will be calc ulate d b y first s u btracti n g t he baseli ne 
val ue  fr o m  eac h  tri plicate -a vera ge  p ost -d ose  meas ure me nt  t o  gi ve  t he  c ha n ge  fr o m  
baseli ne. T he ma xi m u m of t hese val ues o ver t he res pecti ve peri o d will t he n be selecte d, 
e xce pt i n t he case w here a partici pa nt d oes n ot s h o w a n i ncrease. I n s uc h a n i nsta nce, t he 
mi ni m u m decrease s h o ul d be ta ke n.  
3. 6.  Ot her E n d p oi nt(s)  
If d o ne, t he d at a c ollecte d f or t aste assess me nt (i n P A R T - 3) usi n g t he s p o ns or- pr ovi de d 
t aste q uesti o n n aire will be n u meric ally derive d by me as uri n g le n gt h ( usi n g a sc ale wit h 
gr a d ati o ns of at le ast 0. 1 ce nti meter) of t he “x ” m arke d by t he p artici p a nt rel ative t o t he 
“ g o o d tr ait ”.  
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 7 of 5 5 
If perf or me d, bl o o d sa m ples f or t he meas ure me nt of 4β - h y dr o x yc h olester ol, c h olester ol, 
rati o of 4β - h y dr o x yc h olester ol:c h olester ol a n d ot her P K bi o mar kers will be c ollecte d at 
ti mes s pecifie d i n t he S o A gi ve n i n t he pr ot oc ol i n P A R T - 2. Baseli ne will be t he sa m ple o n 
Da y 1 , pri or t o m or ni n g d osi n g a n d t he rati os of Da y 1 0 t o Da y 1  will be calc ulate d.  
I n P A R T- 2: M A D p orti o n of t he st u dy c o n d ucte d at N H C R U o nly, ex pl or at ory 
micr os a m pli n g P K bl o o d s a m ples   f or t he me as ure me nt of P F- 0 7 8 1 7 8 8 3 c o nce ntr ati o ns 
m ay be c ollecte d.  
4.  A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S ) 
Data f or all partici pa nts will be assesse d t o deter mi ne if partici pa nts meet t he criteria f or 
i ncl usi o n i n eac h a nal ysis p o p ulati o n pri or t o u n bli n di n g a n d releasi n g t he data base a n d 
classificati o ns will be d oc u me nte d per sta n dar d o perati n g pr oce d ures. 
T he st u d y part referre d t o bel o w ca n be eit her P A R T - 1: S A D, P A R T - 2: M A D, P A R T - 3: 
R B A / F E, P A R T - 4: M E, P A R T -5: D DI , or  P A R T - 6: S E. 
 
P o p ul ati o n  
Descri pti o n  
E nr olle d  
" E nr olle d" me a ns a p artici p a nt's, a gree me nt t o p artici p ate i n a 
cli nic al st u dy f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt 
pr ocess a n d assi g n me nt t o st u dy i nterve nti o n. A p artici p a nt 
will be c o nsi dere d e nr olle d if t he i nf or me d c o nse nt is n ot 
wit h dr a w n pri or t o p artici p ati n g i n a ny st u dy activity. P ote nti al 
p artici p a nts w h o are scree ne d f or t he p ur p ose of deter mi ni n g 
eli gi bility f or t he st u dy, b ut d o n ot p artici p ate i n t he st u dy, are 
n ot c o nsi dere d e nr olle d, u nless ot her wise s pecifie d by t he 
pr ot oc ol. 
Ev al u a ble 
All p artici p a nts r a n d o mly assi g ne d t o st u dy i nterve nti o n a n d 
w h o t ake at le ast 1 d ose of st u dy i nterve nti o n f or t he give n p art 
of t he st u dy .  
S afety  
All p artici p a nts r a n d o mly assi g ne d t o st u dy i nterve nti o n a n d 
w h o t ake at le ast 1 d ose of st u dy i nterve nti o n. P artici p a nts will 
be a n alyze d acc or di n g t o t he pr o d uct t hey act u ally receive d . 
P K C o nce ntr ati o n Set  
All p artici p a nts r a n d o mly assi g ne d t o st u dy i nterve nti o n a n d 
w h o t ake at le ast 1 d ose of st u dy i nterve nti o n a n d i n w h o m at 
le ast 1 c o nce ntr ati o n v al ue is re p orte d f or t he give n p art of t he 
st u dy. 
P K P ar a meter Set  
A ll p artici p a nts r a n d o mly assi g ne d t o st u dy i nterve nti o n a n d 
w h o t ake at le ast 1 d ose of st u dy i nterve nti o n a n d i n w h o m at 
le ast 1 of t he P K p ar a meters of i nterest are re p orte d f or t he 
give n p art of t he st u dy.  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 8 of 5 5 
P o p ul ati o n  
Descri pti o n  
P K Bi o mar ker Set 
All partici pa nts ra n d o ml y ass i g ne d t o st u d y i nter ve nti o n a n d 
w h o ta ke at least 1 d ose of st u d y i nter ve nti o n a n d i n w h o m at 
least 1 of t he P K bi o mar kers of i nterest a n d b ot h pre a n d p ost 
P F - 0 7 8 1 7 8 8 3 d ose meas ure me nts are re p orte d f or P A R T - 2: 
M A D.  
5.  G E N E R A L M E T H O D O L O G Y  A N D C O N V E N TI O N S  
5. 1.  H y p ot heses a n d Decisi o n R ules  
T here is n o statistical h y p ot hesis testi n g pla n ne d f or t his st u d y a n d n o statistical decisi o n 
r ules will be a p plie d. 
5. 2.  Ge ner al Met h o ds  
U nless ot her wise state d, all s u m maries a n d pl ots will be prese nte d b y treat me nt.  
5. 2. 1.  A n al yses f or C o nti n u o us E n d p oi nts  
C o nti n u o us varia bles will be prese nte d usi n g s u m mar y statistics: n u m ber of o bser vati o ns, 
arit h metic mea n, sta n dar d de viati o n, c v %, me dia n, mi ni m u m a n d ma xi m u m val ues.  
L o g tra nsf or me d c o nti n u o us varia bles will be prese nte d usi n g s u m mar y statistics: n u m ber 
of o bser vati o ns, arit h metic mea n, me dia n, c v %, sta n dar d de viati o n, mi ni m u m, ma xi m u m, 
ge o metric mea n a n d ge o metric c v %.  
5. 2. 2.  A n al yses f or C ate g oric al E n d p oi nts 
Cate g orical varia bles will be prese nte d usi n g s u m mar y statistics: n u m ber of o bser vati o ns 
a n d perce nta ges.  
5. 3.  Met h o ds t o M a n a ge Missi n g D at a 
F or t he a nal ysis of safet y e n d p oi nts, t he s p o ns or data sta n dar d r ules f or i m p utati o n will be 
a p plie d. 
I n all P K data prese ntati o ns (e xce pt listi n gs), c o nce ntrati o ns bel o w t he li mit of 
q ua n tificati o n ( B L Q) will be set t o zer o.  
I n listi n gs, B L Q val ues will be re p orte d as “ < L L Q”, w here L L Q will be re place d wit h t he 
val ue f or t he l o wer li mit of q ua ntificati o n ( L L Q).  
F or P K s u m mar y ta bles a n d pl ots of mea n/ me dia n pr ofiles, statistics will be calc ulate d 
ha vi n g set c o nce ntrati o ns t o missi n g if 1 of t he f oll o wi n g cases is tr ue:  
1.  A c o nce ntrati o n has bee n c ollecte d as N D (ie n ot d o ne) or N S (ie n o sa m ple),  
2.  A de viati o n i n sa m pli n g ti me is of s ufficie nt c o ncer n or a c o nce ntrati o n has bee n 
fla g ge d a n o mal o us b y t he p har mac o ki neticist/statisticia n.  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 2 9 of 5 5 
If a P K para meter ca n n ot be d eri ve d fro m a partici pa nt ’s co n ce ntr ati o n data , t he parameter 
w ill be c o de d a s N C ( ie n ot calcul ate d). ( Note t h at N C val ues w ill n ot be gene rated be y o n d 
t he da y t ha t a partici pa nt dis c o nti n ues) . I n s u m mar y tabl es, statistics w ill be calc ulate d b y 
setti n g N C va l ue s t o missi n g; a n d statistics w ill be present e d for  a pa rticul ar d ose wit h ≥3 
e val ua ble m ea s ure me nts.  
 
If a n i n di vi d ual partici pa nt  has a k n o w n biase d esti mate of a PK p ar a meter ( d u e f or 
e xa m ple to an u ne x p ec te d e v ent  s uc h as v o miti n g b efor e all t he  c o m p o u n d is a de q uat el y 
a bs o r be d i n t he b o d y), t his will be  f o ot n ote d i n s um m ar y ta bles a n d will n ot be i nclu d e d i n 
t he ca lc ulatio n of s u m mar y sta tistics or stat istical a nal ys es. 
 
6.  A N A L Y S E S A N D S U M M A RI E S  
Se parate ta bles will be pr o d uce d f or P A R T -1: S A D, P A R T - 2: M A D, P A R T - 3: R B A/ F E, 
P A R T - 4: M E, P A R T - 5: DDI , a n d P A R T - 6: S E u nless ot her wise s pecifie d. Place b o will 
be a se parate  treat me nt gr o u p. I n P A R T - 2, Ja pa nese a n d C hi nese will be se parate treat me nt 
gr o u ps. If t he n u m ber of C hi nese or J a p a nese p artici p a nts i n P A R T- 5  are ≥3, t he pl as m a 
c o nce ntr ati o n, P K p ar a meters of P F- 0 7 8 1 7 8 8 3 a n d safet y data m ay als o be s u m m arize d 
se p ar ately f or C hi nese, J a p a nese a n d Wester n p o p ul ati o n. Ta bles i n P A R T- 5 will be pa ge d 
b y p o p ulati o n e. g. Ja pa nese, N o n- Ja pa nese a n d All. 
6. 1.  Pri m ar y E n d p oi nt(s) 
T he pri mar y e n d p oi nts i n P A R T - 1, P A R T - 2 a n d P A R T - 6 are relate d t o safet y/t olera bilit y 
a n d t heir a nal yses are descri be d Secti o n 6. 6 .  
T he pri mar y e n d p oi nts i n P A R T - 3 a n d P A R T - 5 are t he plas ma P K e n d p oi nts w h ose 
a nal yses are descri be d i n Secti o n 6. 2 . 
T he pri mar y e n d p oi nts i n P A R T - 4 are perce nt rec o ver y a n d c u m ulati ve rec o ver y of dr u g-
relate d material i n uri ne, feces a n d b ot h ro utes c o m bi ne d  base d o n t otal a d mi nistere d d ose. 
T his ma y  be calc ulate d a n d re p orte d se paratel y.  
6. 2.  Sec o n d ar y E n d p oi nt(s)  
T he sec o n dar y e n d p oi nts i n P A R T - 1, P A R T - 2, P A R T - 4 a n d P A R T - 6, as well as t he 
pri mar y e n d p oi nts i n P A R T - 3 a n d P A R T - 5, are relate d t o P K a n d are descri be d herei n. 
N o f or m al i nfere nti al st atistics will be a p plie d t o t he pl as m a P K d at a a p art fr o m t he 
c o m p aris o ns of f or m ul ati o n a n d f o o d effect i n eit her P A R T- 1  or P A R T - 3 a n d t he 
esti m ati o n of t he effect of ste a dy -st ate P F- 0 7 8 1 7 8 8 3 o n t he P K of mi d az ol a m i n P A R T - 5. 
T he P K d at a f or P F- 0 7 8 1 7 8 8 3 a n d Mi d az ol a m (P A R T- 5 ) will be re p orte d se p ar ately.  
T he P K para meters detaile d i n Secti o n 3. 3. 1  will be liste d a n d s u m marize d f or partici pa nts 
i n t he P K Para meter Set (as defi ne d i n Secti o n 4 ). Missi n g val ues will be ha n dle d as 
detaile d i n Secti o n 5. 3 . Eac h P K para meter will be s u m marize d b y matri x ( plas ma or 
uri ne), treat me nt a n d d ose. Eac h s u m mar y will i ncl u de t he set of s u m mar y statistics as 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 0 of 5 5 
s pecifie d i n Ta ble  7. S u m maries will be perf or me d se paratel y f or P A R T - 1, P A R T - 2, 
P A R T - 3, P A R T - 4, P A R T - 5 a n d P A R T - 6. 
T a ble 7. 
P K P ar a meters t o be S u m m arize d Descri pti vel y   
 
P ar a meter  
S u m m ar y St atistics  
A U C last, A U Ci nf, Cma x , , 
A U C last( d n), A U Ci nf ( d n), 
C ma x ( d n), A U Cτ, C L/ F, Vz/ F , 
C a v, C1 2, Rac, Rac, C ma x, P T R, 
A U C τ ( d n), Aeτ, Aeτ%, a n d 
C L r 
N, arit h metic mea n, me dia n, c v %, sta n dar d de viati o n, 
mi ni m u m, ma xi m u m, ge o metric mea n a n d ge o metric 
c v %. 
T ma x  
N, me dia n, mi ni m u m, ma xi m u m.  
t1/ 2 ,  
N, arit h metic mea n, me dia n, sta n dar d de viati o n, 
mi ni m u m, ma xi m u m.  
T o assess t he relati o ns hi p bet wee n t he P K para meters a n d d ose, d ose n or malize d C ma x , 
A U C last, a n d A U Ci nf  (P A R T - 1) a n d Cma x  a n d A U C τ (P A R T - 2) of P F- 0 7 8 1 7 8 8 3 will be 
pl otte d a gai nst d ose ( usi n g a l o garit h mic scale), a n d will i ncl u de i n di vi d ual partici pa nt 
val ues a n d t he ge o metric mea ns f or eac h d ose. Ge o metric mea ns will ha ve a differe nt 
s y m b ol t ha n t he i n di vi d ual val ues. I n P A R T - 2, t he data fr o m t he Ja pa nese a n d C hi nese 
s u bjects will be i de ntifie d b y differe nt s y m b ols/c ol o urs. T he val ues will be d ose n or malize d 
(t o a 1 m g d ose) b y di vi di n g t he i n di vi d ual val ues a n d ra w ge o metric mea ns b y d ose. A 
f o ot n ote will be a d de d t o t he pl ots t o i n dicate t hat ge o metric mea ns are prese nte d. All d ose 
n or malize d para meters will be liste d al o n g wit h ot her i n di vi d ual P K para meters.  
F or P A R T - 5, b o x a n d w his ker pl ots f or i n di vi d ual partici pa nt para meters ( A U C i nf, A U Clast 
a n d C ma x ) will be prese nte d b y treat me nt a n d o verlai d wit h ge o metric mea ns. 
S u p p orti n g data fr o m t he esti mati o n of t ½ will be liste d b y treat me nt a n d d ose w here 
a p plica ble: ter mi nal p hase rate c o nsta nt ( k el); g o o d ness of fit statistic fr o m t he l o g-li near 
re gressi o n (r2); t he perce nt of A U Ci nf base d o n e xtra p olati o n ( A U Ce xtra p %); a n d t he first, 
last, a n d n u m ber of ti me p oi nts use d i n t he esti mati o n of kel. T hese data ma y be i ncl u de d i n 
t he C S R.  
Prese ntati o ns f or P F- 0 7 8 1 7 8 8 3/ mi daz ola m  c o nce ntrati o ns will be prese nte d usi n g 
partici pa nts i n t he P K C o nce ntrati o n Set (as defi ne d i n Secti o n 4 ) a n d will i ncl u de: 
•  a listi n g of all c o nce ntrati o ns s orte d b y partici pa nt I D, d ose, matri x a n d n o mi nal ti me 
p ost- d ose.  T he c o nce ntrati o n listi n g will als o i ncl u de t he act ual ti mes. De viati o ns fr o m 
t he n o mi nal ti me will be gi ve n i n a se parate listi n g. 
•  a s u m mar y of c o nce ntrati o ns b y d ose a n d n o mi nal ti me p ost- d ose, w here t he set of 
statistics will i ncl u de n, mea n, me dia n, sta n dar d de viati o n, c oefficie nt of variati o n (c v), 
mi ni m u m, ma xi m u m a n d t he n u m ber of c o nce ntrati o ns a b o ve t he l o wer li mit of 
q ua ntificati o n. 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 1 of 5 5 
•  i n di vi d ual c o nce ntrati o n-ti me pl ots b y d ose ( o n b ot h li near a n d se mi-l o g scales) a gai nst 
act ual ti me p ost -d ose (t here will be se parate s pa g hetti pl ots f or eac h d ose per scale).  
•  i n di vi d ual c o nce ntrati o n-ti me pl ots b y partici pa nt ( o n b ot h li near a n d se mi-l o g scales) 
a gai nst act ual ti me p ost - d ose (t here will be se parate s pa g hetti pl ots f or eac h d ose per 
scale). 
•  me dia n c o nce ntrati o n -ti me pl ots ( o n b ot h li near a n d se mi-l o g scales) a gai nst n o mi nal 
ti me p ost- d ose b y d ose (all d oses o n t he sa me pl ot per scale, base d o n t he s u m mar y of 
c o nce ntrati o ns b y d ose a n d ti me p ost- d ose). 
•  mea n c o nce ntrati o n -ti me pl ots ( o n b ot h li near a n d se mi-l o g scales) a gai nst n o mi nal 
ti me p ost- d ose b y d ose (all d oses o n t he sa me pl ot per scale, base d o n t he s u m mar y of 
c o nce ntrati o ns b y d ose a n d ti me p ost- d ose). 
T he scale use d f or t he x- a xis (ti me) of t hese pl ots will be deci de d o n re vie w of t he data, a n d 
will  de pe n d  o n  h o w  l o n g  P F - 0 7 8 1 7 8 8 3/mi daz ola m  c o nce ntrati o n  is  q ua ntifia ble  i n  t he  
matri x.  
F or s u m mar y statistics, me dia n a n d mea n pl ots b y sa m pli n g ti me, t he n o mi nal P K sa m pli n g 
ti me will be use d. F or i n di vi d ual partici pa nt pl ots b y ti me, t he act ual P K sa m pli n g ti me will 
be use d. 
F or P A R T - 2 a n d P A R T - 5, uri ne a m o u nts of P F- 0 7 8 1 7 8 8 3 as liste d i n Ta ble  6 will be 
liste d a n d s u m marize d descri pti vel y, if data per mit. 
F or P A R T- 3 , n at ur al l o g tr a nsf or me d A U Cl ast, Cm ax , a n d A U Ci nf (if d at a per mit) f or P F-
0 7 8 1 7 8 8 3 will be a n alyze d usi n g a mixe d effec t m o del wit h se q ue nce, peri o d, a n d tre at me nt 
i ncl u de d as fixe d effects a n d p artici p a nt neste d wit hi n se q ue nce as a r a n d o m effect. T he 
Ke n war d - R o ger a dj ust me nt f or t he de grees of free d o m will be use d. Esti m ates of t he 
a dj uste d me a n differe nces ( Test -Refere n ce) a n d c orres p o n di n g 9 0 % CIs will be o bt ai ne d 
fr o m t he m o del. T he a dj uste d me a n differe nces a n d 9 0 % CIs f or t hese differe nces will be 
ex p o ne nti ate d t o pr ovi de esti m ates of t he r ati o of a dj uste d ge o metric me a ns 
( Test/ Refere nce) a n d 9 0 % CIs f or t hese r ati os. Only t he first 3 peri o ds will be use d i n t his 
a n alysis (ie, Fe d f or m ul ati o ns excl u de d).  
T o c o m p are t he Fe d a n d F aste d f or m ul ati o ns, n at ur al l o g tr a nsf or me d A U C l ast, Cm ax , a n d 
A U C i nf (if d at a per mit) f or P F- 0 7 8 1 7 8 8 3 fr o m t hese t w o f or m ul ati o ns will be a n alyze d 
se p ar ately usi n g a p aire d t-test. Res ulti n g esti m ates of t he me a n differe nces ( Test - 
Refere nce) a n d c orres p o n di n g 9 0 % CIs fr o m t he t- test will be ex p o ne nti ate d t o pr ovi de 
esti m ates of t he r ati o of ge o metric me a ns ( Test/ Refere nce) a n d  9 0 % CIs f or t he r ati os. 
F or m ul ati o n F aste d is t he Refere nce tre at me nt a n d F or m ul ati o n Fe d is  t he Test tre at me nt. 
 
T he f oll o wi n g c o m p aris o ns will be m a de ( w here a p plic a ble): 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 2 of 5 5 
C o m p aris o n  
T est  
Ref ere nce  
F or m ul ati o n  P F -0 7 8 1 7 8 8 3 Or al F or m ul ati o n 1 i n F aste d 
st ate 
P F -0 7 8 1 7 8 8 3 Or al S us pe nsi o n i n F aste d st ate ( A) 
 
P F -0 7 8 1 7 8 8 3 Or al F or m ul ati o n 2 i n F aste d 
st ate 
P F -0 7 8 1 7 8 8 3 Or al S us pe nsi o n i n F aste d st ate ( A) 
F o o d  Effect  P F -0 7 8 1 7 8 8 3 Or al F or m ul ati o n 1 i n F e d 
( hi g h f at hi g h- c al orie me al ) st ate 
P F -0 7 8 1 7 8 8 3 Or al F or m ul ati o n 1 i n F aste d st ate  
 
P F -0 7 8 1 7 8 8 3 Or al F or m ul ati o n 2 i n F e d 
( hi g h f at hi g h- c al orie me al ) st ate 
P F -0 7 8 1 7 8 8 3 Or al F or m ul ati o n 2 i n F aste d st ate  
 
F or P A R T- 5 , n at ur al l o g tr a nsf or me d A U Cl ast, Cm ax  a n d A U Ci nf (if d at a per mit) of mi d az ol a m 
will be a n alyze d usi n g a mixe d effect m o del wit h se q ue nce, peri o d a n d tre at me nt as fixe d 
effects a n d p artici p a nt neste d wit hi n se q ue nce as a r a n d o m effect. Esti m ates of t he a dj uste d 
me a n differe nces ( Test -Refere nce) a n d c orre s p o n di n g 9 0 % CIs will be o bt ai ne d fr o m t he 
m o del. T he a dj uste d me a n differe nces a n d 9 0 % CIs f or t he differe nces will be ex p o ne nti ate d 
t o pr ovi de esti m ates of t he r ati o of a dj uste d ge o metric me a ns ( Test/ Refere nce) a n d 9 0 % CIs 
f or t he r ati os. Mi d az ol a m al o ne is t he Refere nce tre at me nt w hilst mi d az ol a m + P F- 0 7 8 1 7 8 8 3 
is t he Test tre at me nt. 
If  t he  n u m ber  of  C hi nese  or  J a p a nese  p artici p a nts  i n  P A R T- 5  are  ≥3,  t he  pl as m a 
c o nce ntr ati o n a n d P K p ar a meters of P F -0 7 8 1 7 8 8 3 m ay als o be s u m m arize d se p ar ately f or 
C hi nese, J a p a nese a n d Wester n p o p ul ati o n.  
6. 3.  Ot her E n d p oi nts  
6. 3. 1.  F o o d Effect i n P A R T- 1 : S A D 
If perf or me d, t o assess a n y effect of f o o d/f or m ulati o n i n P A R T - 1, nat ural l o g tra nsf or me d 
A U C last, Cma x , a n d A U Ci nf (if data per mit) f or P F-0 7 8 1 7 8 8 3 will be a nal yze d usi n g a mi xe d 
effects m o del wit h treat me nt as a fi xe d effect a n d partici pa nt as a ra n d o m e ffect usi n g 
partici pa nts wit h data fr o m rele va nt  peri o ds o nl y. 
6. 3. 2.  P K Bi o m ar k er i n P A R T- 2: M A D 
A bs ol ute val ues a n d  t he rati os of Da y 1 0 t o Da y 1 f or P K bi o mar kers i ncl u di n g plas ma 4β -
h y dr o x yc h olester ol/c h olester ol rati o will be s u m marize d descri pti vel y b y treat me nt a n d 
ti me p oi nt, as descri be d i n Secti o n 5. 2. 1 . T he P K bi o mar ker a nal ysis set (as defi ne d i n 
Secti o n 4 ) will be use d. I n di vi d ual pl ots will be create d b y partici pa nt a gai nst act ual ti me 
p ost- d ose (t here will be se parate s pa g hetti pl ots f or eac h treat me nt) o verlai d wit h t he 
me dia n.  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 3 of 5 5 
6. 3. 3.  T aste Assess me nt  i n P A R T - 3: r B A/ F E 
I n P A R T - 3, the t aste attri b utes fr o m t he t aste q uesti o n n aires ( A p pe n dix 1 ) will be liste d 
a n d descri ptively s u m m arize d a n d a p pr o pri ate pl ots m ay be ge ner ate d. T he s u m m ary a n d 
a n alysis of t he t aste assess me nts m ay n ot be re p orte d i n t he C S R.  T he mea n val ue f or eac h 
taste assess me nt sc ore calc ulate d at eac h ti me p oi nt will be re p orte d i n a ra dial pl ot (e g 1 
ra dial pl ot i ncl u di n g all  ti me p oi nts, wit h se parate ra dial pl ots f or eac h treat me nt ). Paire d t-
tests will be perf or me d c o m pari n g treat me nts b y ti me.   
 
6. 3. 4.  Met a b olic Pr ofili n g i n P A R T- 4: M E  
Q ualitati ve c haracterizati o n of meta b olites of P F - 0 7 8 1 7 8 8 3, q ua ntitati ve e xcreti o n of dr u g 
relate d material usi n g 1 9F- N M R s pectr osc o p y, meta b olic pr ofili n g/i de ntificati o n a n d 
deter mi nati o n of relati ve a b u n da nce of P F - 0 7 8 1 7 8 8 3 a n d its meta b olites will be a nal yse d 
se paratel y a n d ma y be i ncl u de d i n t he C S R i n a n a p pe n di x.  
6. 3. 5.  P K b y Micr os a m pli n g  i n P A R T- 2: M A D 
At eac h n o mi nal ti me  p oi nt wit h c o nc urre nt micr osa m pli n g a n d ve ni p u nct ure plas ma 
sa m ple, bl o o d t o plas ma ( B/ P) rati o will be calc ulate d b y di vi di n g w h ole bl o o d P F-
0 7 8 1 7 8 8 3 c o nce ntrati o n wit h t he plas ma P F - 0 7 8 1 7 8 8 3 c o nce ntrati o n. A ge o metric mea n 
B/ P rati o of all sa m ples  will be calc ulate d  f or eac h i n di vi d ual as well f or t he p o p ulati o n.  
T he plas ma P F - 0 7 8 1 7 8 8 3 c o nce ntrati o n b y micr osa m pli n g  (referre d as Tass o P K) will be 
calc ulate d b y di vi di n g w h ole bl o o d c o nce ntrati o n wit h i n di vi d ual ge o metric mea n B/ P 
rati o. As a se nsiti vit y a nal ysis, t he Tass o P K  will als o be calc ulate d usi n g p o p ulati o n 
ge o metric mea n B/ P rati o. S u m mar y statistics ( N, ge o metric mea n, ge o metric C V, me dia n, 
arit h metic mea n, C V, mi ni m u m, ma xi m u m) of  t he w h ole bl o o d c o nce ntrati o ns, plas ma 
c o nce ntrati o ns b y micr osa m pli n g usi n g i n di vi d ual B/ P rati o a n d plas ma c o nce ntrati o n b y 
micr osa m pli n g usi n g ge o metric mea n B/ P rati o  at n o mi nal ti me of c ollecti o n as defi ne d i n 
S o A f or eac h treat me nt ar m will be calc ulate d.  
T he c o nc or da nce a nal yses bet wee n plas ma P K sa m ple a n d b ot h sets of Tass o P K sa m ple 
(calc ulate d usi n g i n di vi d ual or p o p ulati o n ) as descri be d bel o w will be perf or me d. 
Bla n d- Alt ma n pl ots will be pr o d uce d t o l o o k at t he c o nsiste nc y bet wee n P K sa m ple a n d 
Tass o P K sa m ple . Pl ots of t he differe nce bet wee n t he t w o sa m ples  ( o n Y-a xis) as a f u ncti o n 
of t he a vera ge of t he t w o sa m ples ( o n X-a xis). T hese pl ots will be c ol o ure d b y partici pa nt 
i n a d diti o n t o b y ti me p oi nt.  I n a d diti o n, a c orrelati o n pl ot of t he P K sa m ple ( o n X-a xis) a n d 
Tass o P K sa m ple ( o n Y- a xis) will be create d i ncl u di n g a li ne of e q ualit y Y = X. 
6. 3. 6.  E x pl or at or y A n al ysis fr o m P A R T- 6 : S E 
6. 3. 6. 1.  P K of M o xifl o x aci n 
T he M o xifl o xaci n P K para meters detaile d i n Secti o n 3. 3. 1  will be liste d a n d s u m marize d 
f or partici pa nts i n t he P K Para meter Set (as defi ne d i n Secti o n 4 ). Missi n g val ues will be 
ha n dle d as detaile d i n Secti o n 5. 3 . Eac h s u m mar y will i ncl u de t he set of s u m mar y statistics 
as s pecifie d i n Ta ble  7. 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 4 of 5 5 
F or P A R T- 6 - prese ntati o ns  f or m o xifl o xaci n c o nce ntrati o ns will be prese nte d  usi n g 
partici pa nts i n t he P K C o nce ntrati o n Set (as defi ne d i n Secti o n  4 ) a n d will i ncl u de: 
•  a listi n g of all c o nce ntrati o ns s orte d b y partici pa nt I D, n o mi nal ti me p ost- d ose.  T he 
c o nce ntrati o n lis ti n g will als o i ncl u de t he act ual ti mes. De viati o ns fr o m t he n o mi nal 
ti me will be gi ve n i n a se parate listi n g. 
•  a s u m mar y of c o nce ntrati o ns b y n o mi nal ti me p ost- d ose, w here t he set of statistics will 
i ncl u de n, mea n, me dia n, sta n dar d de viati o n, c oefficie nt of variati o n (c v), mi ni m u m, 
ma xi m u m a n d t he n u m ber of c o nce ntrati o ns a b o ve t he l o wer li mit of q ua ntificati o n.  
•  me dia n c o nce ntrati o n -ti me pl ots ( o n b ot h li near a n d se mi-l o g scales) a gai nst n o mi nal 
ti me p ost- d ose . 
T he scale use d f or t he x -a xis (ti me) of t hese pl ots will be deci de d o n re vie w of t he data, a n d 
will de pe n d o n h o w l o n g m o xifl o xaci n  c o nce ntrati o n is q ua ntifia ble i n t he matri x.  
F or s u m mar y statistics, me dia n a n d mea n pl ots b y sa m pli n g ti me, t he n o mi nal P K sa m pli n g 
ti me will be use d. F or i n di vi d ual partici pa nt pl ots b y ti me, t he act ual P K sa m pli n g ti me will 
be use d. 
6. 3. 6. 2.  C o nce ntr ati o n- Q Tc M o dels  ( P A R T- 6: S E o nl y) 
P K/ P D m o del will be esta blis he d t o c haracterize t he relati o ns hi p bet wee n a nal yte (eit her 
P F - 0 7 8 1 7 8 8 3 or m o xifl o xaci n) plas ma c o nce ntrati o n a n d c ha n ge fr o m baseli ne i n heart 
rate-c orrecte d Q T i nter val ( Δ Q Tc) i n t his st u d y. C ha n ge fr o m baseli ne i n Fri derici a’s heart -
rate c orrecte d Q T i nter val ( Δ Q Tc F) will be defa ult de pe n de nt varia ble. Base d o n t he 
rec o m me n dati o n i n t he W hite Pa per 2 p u blis he d rece ntl y o n c o nce ntrati o n-Q Tc ( C -Q Tc) 
m o deli n g, t he li near mi xe d effect m o del is preferre d, it is pre -s pecifie d as 
∆𝑸𝑸𝑻𝑻𝑻𝑻𝒊𝒊𝒊𝒊𝒊𝒊= ( 𝜽𝜽0 + 𝜼𝜼𝟎𝟎,𝒊𝒊)  + 𝜽𝜽1 𝑻𝑻𝑻𝑻𝑻𝑻𝒊𝒊+ ( 𝜽𝜽2 + 𝜼𝜼𝟐𝟐,𝒊𝒊)𝑪𝑪𝒊𝒊𝒊𝒊𝒊𝒊+ �
𝜽𝜽𝟑𝟑𝒊𝒊
𝑲𝑲
𝒊𝒊= 𝟏𝟏
𝑻𝑻𝑻𝑻𝑻𝑻𝑻𝑻𝑘𝑘
+ 𝜽𝜽4 �𝑸𝑸𝑻𝑻𝑻𝑻𝒊𝒊𝒊𝒊𝟎𝟎−𝑸𝑸𝑻𝑻𝑻𝑻𝟎𝟎
��������+ 𝜺𝜺𝒊𝒊𝒊𝒊𝒊𝒊 
Δ Q Tc ij k is t he c ha n ge fr o m baseli ne i n Q Tc f or partici pa nt i, i n treat me nt j, at ti me k; j = 1 
f or acti ve dr u g/ m o xifl o xaci n a n d 0 f or place b o; Cij k is 0 f or place b o; θ0 is t he p o p ulati o n 
mea n i nterce pt i n t he a bse nce of a treat me nt effect; θ 0,i is t he ra n d o m effect ass ociate d wit h 
t he i nterce pt ter m θ0; θ1 is t he fi xe d effect ass ociate d wit h treat me nt T R Tj; θ2 is t he 
p o p ulati o n mea n sl o pe of t he ass u me d li near ass ociati o n bet wee n c o nce ntrati o n a n d 
Δ Q Tc ij k; ƞ2,i is t he ra n d o m effect ass ociate d wit h t he sl o pe θ2; θ3 k is t he fi xe d effect 
ass ociate d wit h ti me k a n d TI M E k is a n i n dicat or varia ble f or t he n o mi nal ti me k 
( k = 1, 2, … K); a n d θ4 is t he fi xe d effect ass ociate d wit h baseli ne Q Tc ij 0; 𝑄𝑄𝑄𝑄𝑐𝑐0
������� is o verall 
mea n of Q Tc ij 0, ie, mea n of all t he baseli ne ( = ti me 0) Q Tc val ues; Ass u m pti o ns f or ra n d o m 
effect ter ms a n d resi d uals: ( ƞ 0,i, ƞ2,i)’ ~ n or mal distri b uti o n wit h mea n ( 0, 0) a n d 
u nstr uct ure d c o varia nce matri x, w hereas t he resi d uals ε ij k are n or mall y distri b ute d wit h 
mea n 0 a n d varia nce σ 2. 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 5 of 5 5 
It f oll o ws fr o m t he W hite Pa per
2 o n c o nce ntrati o n -Q Tc m o deli n g t hat f o ur basic 
ass u m pti o ns will be e val uate d usi n g si m ple gra p hics. Details of t hese gra p hics are 
descri be d i n Secti o n 6. 6. 4. 1. 2 . 
6. 3. 6. 3.  E v al u ati o n of Ass u m pti o ns - Li ne ar Mi xe d Effect M o del  ( P A R T- 6: S E o nl y) 
Acc or di n g t o t he W hite Pa per
3 o n c o nce ntrati o n- Q Tc m o deli n g, t he f oll o wi n g ass u m pti o ns 
f or t he li near mi xe d effect m o del will be e val uate d usi n g e x pl orat or y pl ots. 
o 
Ass u m pti o n 1 : n o dr u g effect o n H R. 
T he ti me c o urse of mea n c ha n ge fr o m baseli ne i n H R a n d / or place b o-a dj uste d 
c ha n ge fr o m baseli ne H R b y treat me nt will be pl otte d t o e val uate t he p ote ntial 
effect of P F- 0 7 8 1 7 8 8 3 / m o xifl o xaci n o n H R. 
o 
Ass u m pti o n 2 : Q Tc F i nter val is i n de pe n de nt of H R. 
A scatter pl ot of Q Tc F vs. R R i nter vals b y treat me nt a n d a Q Tc F - R R q ua ntile pl ot 
will be ge nerate d t o c o nfir m t he a p pr o priate ness o f Fr idericia’s  heart-rate c orrecti o n 
met h o d. 
o 
Ass u m pti o n 3 : N o ti me dela y bet wee n dr u g c o nce ntrati o n a n d Δ Q Tc F. P K/ P D 
h ysteresis will e val uate d usi n g f oll o wi n g e x pl orat or y pl ots: 
L o n git u di nal pl ot of mea n a n d 9 0 % CI f or Δ Q Tc F a n d/ or place b o -a dj uste d Δ Q Tc F 
( Δ Δ Q Tc F) a n d c o nce ntrati o n of P F- 0 7 8 1 7 8 8 3/ m o xifl o xaci n. 
Pl ot of mea n Δ Δ Q Tc a n d c o nce ntrati o n c o n necte d i n te m p oral or der f or P F -
0 7 8 1 7 8 8 3/ m o xifl o xaci n.  
Scatter pl ot of paire d Δ Δ Q Tc F a n d c o nce ntrati o n of P F - 0 7 8 1 7 8 8 3/ m o xifl o xaci n. 
o 
Ass u m pti o n 4 : Li near C o nce ntrati o n- Δ Q Tc F relati o ns hi p.  
T he li nearit y will be assesse d b y a scatter pl ot of paire d Δ Δ Q Tc F a n d c o nce ntrati o n 
b y treat me nt i nc or p orati n g a tre n d li ne (e. g. l oess s m o ot h or li near re gressi o n). 
If e x pl orat or y pl ots i n dicate t he m o deli n g ass u m pti o ns f or t he li near m o del are n ot met, 
a d diti o nal m o deli n g ste ps will be perf or me d t o deter mi ne a n a p pr o priate C -Q Tc m o del.  
o 
If t here is a p ote ntial dela y bet wee n P F- 0 7 8 1 7 8 8 3/ m o xifl o xaci n c o nce ntrati o n a n d 
t he effect o n Q Tc F, a n alter nati ve m o del wit h a dela ye d effect will be c o nsi dere d t o 
acc o u nt f or t he dela y. 
o  
If a li near relati o ns hi p bet wee n P F- 0 7 8 1 7 8 8 3 c o nce ntrati o n a n d t he effect o n Q Tc F 
is n ot s u p p orte d b y e x pl orat or y pl ots, or li near m o dels ca n n ot descri be t he o bser ve d 
data well, n o nli near  m o dels will be a da pte d. E ma x m o dels descri be d i n Secti o n 0  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 6 of 5 5 
ma y be use d , h o we ver, ot her t y pes of P D m o dels ma y be e x pl ore d t o o pti mize t he 
m o del fit.  
o  
If a p pare nt relati o ns hi p bet wee n Q Tc F a n d R R i nter val a n d/ or differe nces 
distri b uti o n of H R bet wee n o n- a n d off- dr u g c o n diti o ns are o bser ve d i n e x pl orat or y 
pl ots, ot her a p pr oac hes t o e val uate Q T/ Q Tc ma y be c o nsi dere d as s u m marize d i n 
t he met h o d ol o g y pa per b y Gar nett et al 3. 
6. 3. 6. 4.  C o nce ntr ati o n- Q Tc Q u a ntile Pl ot ( P A R T - 6: S E o nl y) 
A c o nce ntrati o n- Δ Q Tc q ua ntile pl ot of o bser ve d data o verlai d wit h t he m o del pre dicti o ns 
is a vis ual assess me nt of h o w well t he m o del fits t he data. I n t his pl ot, t he o bser ve d P F -
0 7 8 1 7 8 8 3/ m o xifl o xa ci n c o nce ntrati o ns are cate g orize d i nt o t heir deciles (e. g. 1 0 bi ns of 
e q ual size) a n d t he mea n c ha n ge fr o m baseli ne Q Tc F i nter vals ( Δ Q Tc F) are calc ulate d f or 
eac h bi n, al o n g wit h t heir 5t h a n d 9 5t h perce ntiles, as well as t he 9 0 % c o nfi de nce i nter val 
f or the mea n.  
6. 3. 6. 5.  M o del Selecti o n a n d E v al u ati o n ( P A R T- 6: S E o nl y) 
T he dr u g effect m o dels  r o uti nel y teste d are t he li near a n d E ma x m o dels. If t he li near 
m o del clearl y d oes n ot ca pt ure t he tre n d of t he data i n t he c o nce ntrati o n -Q Tc F  q ua ntile 
pl ot, t he E ma x m o del s pecifie d bel o w will be fitte d a n d assesse d:  
 
∆𝑸𝑸𝑻𝑻𝑻𝑻𝒊𝒊𝒊𝒊𝒊𝒊= ( 𝜽𝜽0 + 𝜼𝜼𝟎𝟎,𝒊𝒊)  + 𝜽𝜽1 𝑻𝑻𝑻𝑻𝑻𝑻𝒊𝒊+
(𝜽𝜽𝜼𝜼𝟐𝟐+ 𝒊𝒊𝑪𝑪,𝒊𝒊)𝒊𝒊𝒊𝒊𝜽𝜽𝟑𝟑
𝒊𝒊𝑲𝑲𝒊𝒊+ 𝟏𝟏𝑻𝑻𝑻𝑻𝑻𝑻
+ �
𝑻𝑻𝑘𝑘𝜽𝜽
𝑸𝑸
𝑻𝑻= 𝑻𝑻
𝒊𝒊𝒊𝒊𝟎𝟎𝑸𝑸k
+ 𝑻𝑻4 �𝑻𝑻𝟎𝟎𝜺𝜺𝒊𝒊𝒊𝒊𝒊𝒊−𝑄𝑄𝑄𝑄𝑐𝑐𝟎𝟎
��������+ 𝛆𝛆𝐢𝐢𝐢𝐢𝐢𝐢 
 
T he para meter θ 2 1 is t he p o p ulati o n mea n of E C 5 0. T he para meter θ2 2 is t he p o p ulati o n 
mea n  of ma xi m u m effect ( E ma x) wit h a n ass ociate d ra n d o m effect of ƞ 2,i. T he treat me nt 
effect (θ 1) ma y or ma y n ot be i ncl u de d i n t he E ma x m o del. Ass u m pti o ns f or ra n d o m effect 
ter ms a n d resi d uals: (ƞ 0,i, ƞ 2,i)’ ~ n or mal distri b uti o n wit h mea n ( 0, 0) a n d u nstr uct ure d 
c o varia nce  matri x, w hereas t he resi d uals ε ij k are n or mall y distri b ute d wit h mea n 0 a n d 
varia nce σ 2. T he g o o d ness - of-fit of t he E ma x m o del will be c o m pare d wit h t he li near 
mi xe d effect m o del  t hr o u g h re vie w of t he AI C criteria, t he para meter esti mates, resi d ual 
pl ots, c o nce ntrati o n- Δ Q Tc  q ua ntile pl ots a n d ot her dia g n ostic pl ots.  
6. 3. 6. 6.  M o del -b ase d Esti m ati o n of Δ Δ Q Tc F at C o nce ntr ati o n of I nterest ( P A R T - 6: 
S E o nl y) 
T he fi nal C -Q Tc m o del will be use d t o c o m p ute t he Δ Δ Q Tc F at c o nce ntrati o ns of i nterest. 
T he place b o a dj uste d c ha n ge fr o m baseli ne Q Tc F ( Δ Δ Q Tc F) is t he differe nce bet wee n t he 
m o del- esti mate d Δ Q Tc F at c o nce ntrati o n of i nterest a n d t he m o del -esti mate d Δ Q Tc F f or 
place b o (e g. c o nce ntrati o n = 0).  
T he fi nal C -Q Tc m o del para meters will be prese nte d i n ta b ular f or mat s h o wi n g t he 
esti mate, sta n dar d err or of t he esti mate, p - val ue a n d 9 5 % c o nfi de nce i nter val. G o o d ness- of-
fit pl ots will be prese nte d f or t he fi nal C-Q Tc m o del.   A vis ualizat i o n dis pla yi n g t he m o del 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 7 of 5 5 
pre dicte d mea n a n d t he 9 0 % c o nfi de nce i nter val f or t he mea n f or place b o- a dj uste d mea n 
c ha n ge fr o m baseli ne Q Tc F i nter vals ( Δ Δ Q Tc F)  will als o be create d.  
Res ults of t he m o del - base d C- Q Tc a nal yses a n d e x pl orat or y pl ots (as liste d i n Seci o ns 
6. 3. 6. 2 t hr o u g h 6. 3. 6. 6) , m o del selecti o n a n d e val uati o ns, a n d m o del fitti n g statistics, will 
be d oc u me nte d i n a se parate re p ort a n d ma y be i ncl u de d as a n A p pe n di x t o t he C S R. 
6. 3. 6. 7.  Ass a y Se nsiti vit y ( P A R T- 6: S E o nl y) 
C ha n ge fr o m baseli ne i n Q Tc F will be  m o delle d usi n g a re peate d meas ures mi xe d effect 
( M M R M) m o del. All pla n ne d p ost- d ose ti me  p oi nts fr o m t he safet y a nal ysis set u p t o 1 2 0 h 
will be i ncl u de d i n t he m o del. T he m o del will i ncl u de treat me nt, peri o d, ti me (as a fact or), 
treat me nt- b y-ti me i nteracti o n a n d i n di vi d ual baseli ne (f or eac h peri o d) as fi xe d effects, 
s u bject as a ra n d o m effect, a n d ti me re peate d wit hi n eac h partici pa nt * peri o d as a re peate d 
effect. T he Ke n war d - R o ger a dj ust me nt f or t he de grees of free d o m will be use d. A 
c o m p o u n d s y m metr y c ova ria nce matri x will be fitte d t o t he re peate d ti mes wit hi n 
partici pa nt ( ot her c o varia nce matrices will be c o nsi dere d if necessar y, e. g. if t he m o del 
d oes n ot c o n ver ge). 
T he Least S q uares ( L S) mea ns (a n d sta n dar d err ors, 9 0 % c o nfi de nce i nter vals a n d 2- si ded 
p- val ues) will be o btai ne d f or eac h treat me nt at eac h ti me p oi nt. Differe nces (a n d sta n dar d 
err ors, 9 0 % c o nfi de nce i nter vals a n d 2- si de d p-val ues) bet wee n L S mea ns will als o be 
o btai ne d, c o m pari n g eac h treat me nt vers us place b o.  
T he st u d y will be dee me d a de q uatel y se nsiti ve t o detect Q T/ Q Tc pr ol o n gati o n if t he l o wer 
b o u n d of t he 2-si de d 9 0 % CI f or t he L S mea n differe nce bet wee n m o xifl o xaci n a n d place b o 
is greater t ha n 5 ms at 3 h o urs p ost- d ose of m o xifl o xaci n ( hist oric p o p ulati o n Tma x ). 
A d diti o nall y, e x p os ure- res p o nse a nal ysis of baseli ne c orrecte d Q Tc F of m o xifl o xaci n will 
be c o n d ucte d i n a se parate re p ort a n d ma y n ot be i ncl u de d i n t he t he C S R. 
E xa m ple S A S c o de is pr o vi de d i n A p pe n di x 4 . 
Statistical M o del Dia g n ostics  
T he prese nce of o utliers will be i n vesti gate d f or t his m o del. A n o utlier will be defi ne d as 
a n y res p o nse data val ue wit h a st u de ntize d (c o n diti o nal) resi d ual greater t ha n 3, or less t ha n  
3. A listi n g will be prese nte d of a n y partici pa nts meeti n g t hese criteria a n d will be i ncl u de d 
wit h sta n dar d S A S o ut p ut. T he ass u m pti o ns of n or malit y will be verifie d gra p hicall y usi n g 
resi d ual pl ots. F or eac h fitte d m o del, a set of c o n diti o nal st u de ntize d resi d ual pl ots will be 
pr o d uce d, i ncl u di n g resi d ual pl ot, hist o gra m of n or malit y, q uartile- q uartile ( Q Q) pl ot a n d 
s u m mar y of fit statistics. T he resi d ual pl ots will n ot be i ncl u de d i n t he C S R.  
If t here are o utliers or maj or de viati o ns fr o m n or malit y, t he n t he effect of t hese o n t he 
c o ncl usi o ns ma y be i n vesti gate d t hr o u g h alter nati ve tra nsf or mati o ns a n d/ or a nal yses 
e xcl u di n g o utliers. J ustificati o n f or a n y alter nati ve t o t he pla n ne d a nal ysis will be gi ve n i n 
t he re p ort of t he st u d y. 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 8 of 5 5 
6. 4.  S u bset A n al yses  
N o s u bset a n alyses will be perf or me d.  
6. 5.  B aseli ne a n d Ot her S u m m aries a n d A n al yses  
6. 5. 1.  St u d y C o n d uct a n d P artici p a nt Dis p ositi o n  
Partici pa nt e val uati o n gr o u ps will s h o w partici pa nt dis p ositi o n b y treat me nt. Fre q ue nc y 
c o u nts a n d perce nta ges will be s u p plie d f or partici pa nt disc o nti n uati o n(s) b y treat me nt. 
Data will be re p orte d i n acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds. 
6. 5. 2.  De m o gr a p hic D at a 
De m o gra p hic data (a ge, bi ol o gical se x, race, et h nicit y, wei g ht, b o d y mass i n de x a n d hei g ht) 
will be s u m marise d b y c o h ort f or P A R T - 1, P A R T - 3, P A R T - 5 a n d P A R T - 6, b y treat me nt 
f or P A R T - 2 a n d P A R T - 4 a nd o verall (if a p plica ble) i n acc or da nce wit h t he s p o ns or 
re p orti n g sta n dar ds.  
6. 5. 3.  C o nc o mit a nt Me dic ati o ns a n d N o n dr u g Tre at me nts 
All c o nc o mita nt me dicati o n(s) as well as n o n - dr u g treat me nt(s) will be re p orte d acc or di n g 
t o c urre nt s p o ns or re p orti n g sta n dar ds.  
6. 5. 4.  Ot her Scree ni n g D at a  
T hese data will n ot be rec or de d i n t he st u d y data base, a n d t heref ore will n ot be liste d.  
6. 6.  S afet y S u m m aries a n d A n al yses 
I n all 5 parts of t he st u d y, all safet y a nal yses will be perf or me d o n t he Safet y A nal ysis Set.  
6. 6. 1.  A d verse E ve nts 
A d verse e ve nts will be re p orte d i n acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds. 
6. 6. 2.  L a b or at or y D at a  
La b orat or y data will be liste d a n d s u m marize d b y treat me nt i n acc or da nce wit h t he s p o ns or 
re p orti n g sta n dar ds. Baseli ne is as defi ne d i n Secti o n 3. 5. 2 . 
I n di vi d ual partici pa nt pr ofiles will be create d f or t h ose partici pa nts meeti n g t he s p o ns or 
a b n or malit y criteria – i ncl u di n g a bs ol ute val ues, c ha n ge fr o m baseli ne a n d perce nt c ha n ge 
fr o m baseli ne. 
F or P A R T - 1, P A R T - 2, P A R T - 5 a n d  P A R T - 6, cha n ge fr o m baseli ne a n d perce nt c ha n ge 
fr o m baseli ne will be s u m marize d descri pti vel y b y treat me nt a n d ti me p oi nt, as descri be d i n 
Secti o n 5. 2. 1 . T he safet y a nal ysis set (as defi ne d i n Secti o n 4 ) will be use d. Mea n c ha n ge 
fr o m baseli ne a n d perce nt c ha n ge fr o m baseli ne will be pl otte d a gai nst ti me p ost- d ose. O n 
eac h pl ot t here will be o ne li ne f or eac h treat me nt a n d 9 0 % CIs.   
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 3 9 of 5 5 
6. 6. 3.  Vit al Si g ns 
A bs ol ute val ues a n d c ha n ges fr o m baseli ne i n s u pi ne s yst olic a n d diast olic bl o o d press ure, 
p ulse rate  a n d res pirat or y rate will be s u m marize d b y treat me nt a n d ti me p ost - d ose, 
acc or di n g t o s p o ns or re p orti n g sta n dar ds. Ta bles will be pa ge d b y para meter. Baseli ne is as 
defi ne d i n Secti o n 3. 5. 3 . 
Mea n c ha n ges fr o m baseli ne f or s u pi ne s yst olic a n d diast olic bl o o d press ure, p ulse rate, 
te m perat ure a n d res pirat or y rate will be pl otte d a gai nst ti me p ost - d ose. Eac h part will ha ve 
its o w n o ut p ut wit h 1 li ne f or eac h treat me nt. Place b o will be p o ole d i n t he pl ots f or 
P A R T - 1 a n d P A R T - 2, alt h o u g h t he Fe d , Ja pa nese a n d C hi nese place b o i n P A R T - 2 (if 
a p plica ble) will be treate d as se parate treat me nt  gr o u ps. C orres p o n di n g i n di vi d ual pl ots of 
c ha n ges fr o m baseli ne will als o be pr o d uce d f or eac h treat me nt.  
Ma xi m u m decrease fr o m baseli ne f or s u pi ne s yst olic a n d diast olic bl o o d press ures a n d 
res pirat or y rate a n d ma xi m u m i ncrease fr o m baseli ne f or s u pi ne p ulse rate a n d te m perat ure 
will be s u m marize d b y treat me nt, acc or di n g t o s p o ns or re p orti n g sta n dar ds. 
Mi ni m u m a n d/ or ma xi m u m a bs ol ute val ues a n d c ha n ges fr o m baseli ne f or s u pi ne vital 
si g ns will als o be s u m marize d descri pti vel y b y treat me nt usi n g cate g ories as defi ne d i n 
A p pe n di x 2 . N u m bers a n d perce nta ges of partici pa nts meeti n g t he cate g orical criteria will 
be pr o vi de d. All pla n ne d a n d u n pla n ne d p ost- d ose ti me p oi nts will be c o u nte d i n t hese 
cate g orical s u m maries.   
I n di vi d ual partici pa nt pr ofiles will be create d f or t h ose participa nts meeti n g t he s p o ns or 
a b n or malit y criteria – i ncl u di n g a bs ol ute val ues, c ha n ge fr o m baseli ne a n d perce nt c ha n ge 
fr o m baseli ne. 
6. 6. 4.  E C G  
A bs ol ute val ues a n d c ha n ges fr o m baseli ne i n Q T, heart rate, Q Tc F, P R a n d Q R S will be 
s u m marize d b y treat me nt a n d ti me p ost- d ose usi n g s p o ns or re p orti n g sta n dar ds. Ta bles will 
be pa ge d b y para meter. Baseli ne is as defi ne d i n Secti o n 3. 5. 4 . 
Mea n c ha n ges fr o m baseli ne i n Q T, heart rate a n d Q Tc F will be pl otte d a gai nst ti me p ost -
d ose. Eac h part will ha ve its o w n o ut p ut wit h 1 li ne f or eac h treat me nt. Place b o will be 
p o ole d i n t he pl ots f or P A R T - 1, P A R T- 6 a n d P A R T - 2, alt h o u g h t he Fe d, Ja pa nese a n d 
C hi nese place b o  i n P A R T - 2 (if a p plica ble) will be treate d as se parate treat me nt gr o u ps. 
C orres p o n di n g i n di vi d ual pl ots of c ha n ges fr o m baseli ne will als o be pr o d uce d f or eac h 
treat me nt. 
Ma xi m u m i ncrease fr o m baseli ne f or Q Tc F will be s u m marize d b y treat me nt, acc or di n g t o 
s p o ns or re p orti n g sta n dar ds.  
E C G e n d p oi nts a n d c ha n ges fr o m baseli ne ( Q Tc F, P R a n d Q R S) will als o be s u m marize d 
descri pti vel y b y treat me nt usi n g cate g ories as defi ne d i n A p pe n di x 2  (f or Q Tc F t hese 
c orres p o n d t o t he Pfizer G ui da nce 1 i n Secti o n 8 ). N u m bers a n d perce nta ges of partici pa nts 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 0 of 5 5 
meeti n g t he cate g orical criteria will be pr o vi de d. All pla n ne d a n d u n pla n ne d p ost d ose ti me 
p oi nts will be c o u nte d i n t hese cate g orical s u m maries.   
I n di vi d ual partici pa nt pr ofiles will be create d f or t h ose partici pa nts meeti n g t he 
s p o ns or’sa b n or malit y criteria – i ncl u di n g a bs ol ute val ues, c ha n ge fr o m baseli ne a n d 
perce nt c ha n ge fr o m baseli ne.  
7.  LI S TI N G S O F P A R TI CI P A N T S WI T H A N Y SI N G L E P O S T - D O S E V A L U E > 5 0 0 
M S E C WI L L A L S O B E P R O D U C E D F O R Q T C F. I N T E RI M A N A L Y S E S  
7. 1.  I ntr o d ucti o n 
N o f or m al i nteri m a n alysis will be c o n d ucte d f or t his st u dy. As t his is a s p o ns or o pe n st u dy, 
t he s p o ns or will c o n d uct u n bli n de d revie ws of t he d at a d uri n g t he c o urse of t he st u dy f or 
t he p ur p ose of s afety assess me nt, f acilit ati n g d ose esc al ati o n decisi o ns, f acilit ati n g P K 
m o deli n g, a n d/ or s u p p orti n g cli nic al devel o p me nt. U n bli n de d res ults will be revie we d by a 
desi g n ate d li mite d n u m ber of s p o ns or c olle a g ues wit hi n t he st u dy te a m. 
7. 2.  I nteri m A n al yses a n d S u m m aries 
N/ A  
8.  R E F E R E N C E S  
1.  Pfizer G ui da nce f or E val uati o n of Q T / Q Tc I nter val Pr ol o n gati o n a n d 
Pr oarr h yt h mic P ote ntial f or N o n- a ntiarr h yt h mic Dr u gs; Me m bers of t he 
Car di o vasc ular Safet y & A d vis or y C o u ncil ( C V S A C); Ja n uar y 2 6, 2 0 1 8 
2.  Gar nett C., et al. Scie ntific w hite pa per o n c o nce ntrati o n -Q Tc  m o deli n g. J o ur nal of 
P har mac o ki net a n d P har mac o d y n Dece m ber 2 0 1 7; htt ps:// d oi. or g/ 1 0. 1 0 0 7/s 1 0 9 2 8-
0 1 7- 9 5 5 8- 5  
3.  Gar nett C., et al. Met h o d ol o gies t o c haracteriz e t he Q T/c orrecte d Q T i nter val i n t he 
prese nce of dr u g -i n d uce d heart  rate c ha n ges or ot her a ut o n o mic effects. A m Heart J 
1 6 3( 6): 9 1 2 - 3 0 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 1 of 5 5 
A P P E N DI C E S  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 2 of 5 5 
 
  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 3 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 4 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 5 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 6 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 7 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 8 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 4 9 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 5 0 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 5 1 of 5 5 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 5 2 of 5 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 5 3 of 5 5 
A p pe n di x  2. Cate g orical Classes f or E C G a n d Vital Si g ns of P ote ntial Cli nical C o ncer n  
C at e g ori es f or Q Tc F  
 
Mil d ( msec)  
M o der ate ( msec)  
Se vere (msec)  
A bs ol ute  val ue  of  
Q T c F  ( msec) 
> 4 5 0  a n d ≤4 8 0  
> 4 8 0  a n d ≤5 0 0  
> 5 0 0  
I ncr ease fr o m baseli ne  
i n Q T c F  ( msec) 
> 3 0  a n d ≤6 0  
> 6 0  
 
 
C at e g ori es f or P R a n d Q R S  
P R ( ms)  
ma x. ≥3 0 0  
 
 
P R ( ms) i ncr ease 
fr o m baseli ne 
Baseli ne > 2 0 0 
a n d ma x. 
≥2 5 % i ncr ease  
Baseli ne ≤2 0 0 a n d 
ma x. ≥5 0 % 
i ncr ease 
Q R S ( ms)  
ma x. ≥1 4 0  
Q R S ( ms) 
i ncr ease fr o m 
baseli ne  
≥5 0 % i ncr ease  
 
C at e g ori es f or Vit al Si g ns  
S yst olic B P ( m m H g)  
mi n. < 9 0  
 
S yst olic B P ( m m H g) 
c ha n ge fr o m baseli ne  
ma x. decr ease ≥3 0  
ma x. i ncr ease ≥3 0  
Diast olic B P ( m m H g)  
mi n. < 5 0  
 
Diast olic B P ( m m H g) 
c ha n ge fr o m baseli ne  
ma x. decr ease ≥2 0  
ma x. i ncr ease ≥2 0  
S u pi ne p ulse r ate ( b p m)  
mi n. < 4 0  
ma x. > 1 2 0  
 
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 5 4 of 5 5 
A p pe n di x  3. List of A b bre vi ati o ns 
A b bre vi ati o n  
Ter m  
A E  
a d verse e ve nt 
A U C  
area u n der t he c ur ve  
B A  
B i oa vaila bilit y 
B L Q  
bel o w t he li mit of q ua ntitati o n 
B P  
bl o o d press ure  
CI  
c o nfi de nce i nter val 
C ma x  
ma xi m u m o bser ve d c o nce ntrati o n  
C R F  
case re p ort f or m 
C S R  
cli nical st u d y re p ort 
D DI  
dr u g -dr u g i nteracti o n  
E C G  
electr ocar di o gra m 
F E  
f o o d effect 
G C P  
G o o d Cli nical Practice  
I C D 
i nf or me d c o nse nt d oc u me nt 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n 
L L O Q  
l o wer li mit of q ua ntitati o n 
L S  
least-s q uares 
M A D  
m ulti ple asce n di n g d ose  
M E  
Meta b olis m a n d E xcreti o n  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
M M R M  
mi xe d -effects m o del wit h re peate d meas ures  
N/ A  
n ot a p plica ble  
P D  
p har mac o d y na mic(s)  
P K  
p har mac o ki netic(s)  
P T  
preferre d ter m  
Q Tc F  
c orrecte d Q T ( Fri dericia met h o d)  
R B A  
relati ve bi oa vaila bilit y 
S A D  
si n gle asce n di n g d ose 
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S D  
sta n dar d de viati o n 
S E  
s u prat hera pe utic e x p os ure 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
 
 
 
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)


Pr ot oc ol C 5 0 9 1 0 0 1 ( P F - 0 7 8 1 7 8 8 3) Statistical A nal ysis Pla n 
 
 
D M B 0 2 -G S O P - R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate  3 1-Ja n- 2 0 2 2 
P FI Z E R  C O N FI D E N TI A L   
T M F D oc I D: 9 8. 0 3  
Pa ge 5 5 of 5 5 
A p pe n di x  4. E x a m ple S A S c o de f or St atistic al A n al yses 
M M R M f or Q Tc F a nal yses:  
Base 1 is t he a vera ge baseli ne f or eac h partici pa nt, base 2 is t he peri o d -a dj uste d baseli ne.  
p r o c  m i x e d  d a t a = p d  m e t h o d = r e m l  o r d e r = d a t a ;  
  
t i t l e 1  " S A S  o u t p u t  M M R M  E n d p o i n t  =  & e n d p o i n t _ n a m e " ;  
  
c l a s s  s u b j i d  t r e a t t x t  t i m e  p e r i o d ;  
  
m o d e l  & v a r = b a s e 1  b a s e 2  p e r i o d  t r e a t t x t  t i m e  
  
t r e a t t x t * t i m e  /  d d f m = k r  r e s i d u a l ;  
  
r e p e a t e d  t i m e  /  s u b j e c t = s u b j i d * p e r i o d  t y p e = u n ;  
  
l s m e a n s  t r e a t t x t  / d i f f  c l  ;  
  
l s m e a n s  t r e a t t x t * t i m e  / d i f f  c l  a l p h a  =  0 . 1 ;  
r u n ;  
0 9 0 1 7 7 e 1 9 d 8 c 5 0 d 2\ Fi n al\ Fi n al O n: 2 4- M a y- 2 0 2 3 1 3: 1 8 ( G M T)