General Investigation for PAXLOVID PAC
Conditions: SARS-CoV-2 Infection
Sponsor: Pfizer

PAXLOVID
C4671018 NON-INTERVENTIONAL STUDY PROTOCOL
Amended 2, 31 January 2023
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PAXLOVID® PACK General Investigation
FULL PROTOCOL
Pfizer Japan Inc.
This document contains confidential information belonging to Pfizer. Except as otherwise agreed 
to in writing, by accepting or reviewing this document, 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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C4671018 NON-INTERVENTIONAL STUDY PROTOCOL
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STUDY INFORMATION
Title
PAXLOVID® PACK General Investigation
Protocol number
C4671018
Protocol version identifier
Version 3
Date
31 January 2023
Active substance
Nirmatrelvir/ritonavir
Medicinal product
PAXLOVID® PACK
Research question and objectives
To assess the safety and effectiveness of 
PAXLOVID under actual status of use.
Author
PPD

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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................3
2. LIST OF ABBREVIATIONS................................................................................................6
3. RESPONSIBLE PARTIES....................................................................................................7
4. AMENDMENTS AND UPDATES.......................................................................................7
5. MILESTONES.......................................................................................................................8
6. RATIONALE AND BACKGROUND..................................................................................9
7. RESEARCH QUESTION AND OBJECTIVES ...................................................................9
7.1. Safety specifications..................................................................................................9
8. RESEARCH METHODS ....................................................................................................10
8.1. Study design ............................................................................................................10
8.2. Setting......................................................................................................................10
8.2.1. Registration criteria ....................................................................................10
8.2.2. Exclusion criteria........................................................................................10
8.2.3. Study sites...................................................................................................10
8.2.3.1. Site requirements.......................................................................10
8.2.4. Planned study period...................................................................................11
8.2.5. Study procedures ........................................................................................11
8.2.5.1. Study method.............................................................................11
8.2.5.2. Request for cooperation in the study and contract ....................11
8.2.6. Observation period......................................................................................11
8.3. Variables..................................................................................................................11
8.3.1. Patient characteristics .................................................................................12
8.3.2. Presence/absence of pregnancy (only for women).....................................15
8.3.3. Presence/absence of findings of pneumonia attributable to infections 
caused by SARS-CoV-2 at the start of administration ....................................15
8.3.4. Hospitalization status..................................................................................15
8.3.5. Targeted drug use record ............................................................................16
8.3.6. Concomitant therapy...................................................................................16
8.3.6.1. Drug therapy..............................................................................16

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8.3.6.2. Non-drug therapy ......................................................................16
8.3.7. Tests/clinical laboratory tests .....................................................................17
8.3.7.1. SARS-CoV-2 viral test..............................................................17
8.3.7.2. Vital signs..................................................................................17
8.3.8. End-of-study / Discontinuation record .......................................................17
8.3.9. Effectiveness evaluation (severity).............................................................18
8.3.10. Adverse events..........................................................................................18
8.4. Data sources ............................................................................................................19
8.5. Study size ................................................................................................................19
8.5.1. Planned sample size....................................................................................19
8.5.2. Rationale for sample size............................................................................19
8.6. Data management....................................................................................................20
8.6.1. Case report forms (CRFs)/ Electronic data record .....................................20
8.6.2. Record retention..........................................................................................20
8.6.3. Data collection method (EDC) ...................................................................20
8.6.4. Patient registration (EDC) ..........................................................................20
8.6.5. Points to consider for completion, revision, and submission of case 
report form (EDC)............................................................................................21
8.6.5.1. Data entry ..................................................................................21
8.6.5.2. Data revision .............................................................................21
8.6.5.3. Submission ................................................................................21
8.7. Data analysis ...........................................................................................................21
8.8. Quality control.........................................................................................................22
8.9. Limitations of the research methods .......................................................................22
8.10. Other necessary matters ........................................................................................22
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................23
9.1. Patient information..................................................................................................23
9.2. Patient consent.........................................................................................................23
9.3. Institutional review board (IRB)/Independent ethics committee (IEC)..................24
9.4. Ethical conduct of the study....................................................................................24

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10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................24
10.1. Requirements for recording and reporting ............................................................24
10.2. Reporting period....................................................................................................26
10.3. Causality assessment.............................................................................................26
10.4. Definitions of safety events...................................................................................26
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........32
12. NAME, AND ADDRESS OF CONTRACTOR AS WELL AS SCOPE OF WORK 
CONTRACTED..................................................................................................................33
13. ADDITIONAL MEASURES THAT MAY BE IMPLEMENTED BASED ON 
THE STUDY RESULTS AND CRITERIA FOR DETERMINATION OF THE 
INITIATION.......................................................................................................................33
14. SCHEDULED TIMING OF MILESTONES AND THEIR RATIONALES FOR 
EVALUATION OF STUDY IMPLEMENTATION STATUS AND RESULTS 
AND REPORTING TO THE PMDA.................................................................................34
15. OTHER NECESSARY MATTERS ..................................................................................34
16. CONTACT INFORMATION............................................................................................34
16.1. Contact information for inquiries about the study ................................................34
16.2. Contact information for inquiries about the EDC system (In the case of 
study using EDC) ......................................................................................................35
17. REFERENCES ..................................................................................................................35
18. LIST OF TABLES.............................................................................................................35
19. LIST OF FIGURES ...........................................................................................................35
ATTACHMENT 1. TABLE OF CONTENTS OF INDEPENDENT DOCUMENTS ...........35
ATTACHMENT 2. ADDITIONAL INFORMATION ...........................................................35

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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
3CL
3C-like protein
COVID-19
Coronavirus disease 2019
EDC
Electronic data capture
FDA
Food and drug administration (United States)
ICH
International conference on harmonisation
IEC
Independent ethics committee 
IRB
Institutional review board
N/A
Not applicable
SAP
Statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2

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3. RESPONSIBLE PARTIES
The Japan Good Post-marketing Study Practice officer
4. AMENDMENTS AND UPDATES
Amendment 
number
Date
Protocol
Section(s)
Changed
Summary of
Amendment(s)
Reason
Amended 2
31 January 
2023
5. MILESTONES
Addition of items and update of 
contents
Administrative 
changes
6. RATIONALE 
AND 
BACKGROUND
Update of ministerial ordinances, 
notifications, etc.
Due to the partial 
revision of the 
ministerial 
ordinance
8.9. Limitations of 
the research 
methods
9.4. Ethical conduct 
of the study
Terminology changes, etc.
Administrative 
changes
10. 
MANAGEMENT 
AND REPORTING 
OF ADVERSE 
EVENTS/ADVERS
E REACTIONS
Changes in Japanese translation, etc., 
and maintenance of descriptions
Due to changes in 
association with a 
revision of the 
in-house form
12. NAME, AND 
ADDRESS OF 
CONTRACTOR AS 
WELL AS SCOPE 
OF WORK 
CONTRACTED
Maintaining address information
Administrative 
changes
16.2. Contact 
information for 
inquiries about the 
EDC system (In the 
case of study using 
EDC)
Changes in contact information for 
inquiries
Due to changes in 
the information 
concerning contact 
information
Amended 1
28 June 
2022
7.1. Safety 
specifications
Added anaphylaxis to important 
identified risks
Due to the 
revision of safety 
specification in 
the Risk 
Management Plan
8.7. Data analysis
1. Definition of analysis set
Change before:
The effectiveness
analysis set was 
not a subset of 
safety populations, 

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•Effectiveness Analysis Set 1: A 
population of patients in the SAS 
excluding patients for whom 
effectiveness evaluation is not reported 
at all or whose disease is not subject to 
the study
After change:
•Effectiveness Analysis Set 1: A 
population of patients in which 
effectiveness can be evaluated among 
patients in which this drug was 
administered
but effectiveness
evaluable among 
all patients with 
administration
10. 
MANAGEMENT 
AND REPORTING 
OF ADVERSE 
EVENTS/ADVERS
E REACTIONS
Changes in Japanese translation, etc., 
and maintenance of descriptions
Due to changes in 
association with a 
revision of the 
in-house form
12. 
ORGANIZATION
AL SYSTEM FOR 
STUDY 
IMPLEMENTATIO
N
Item Removal
(Subsequent section numbers moved 
up)
Administrative 
changes associated 
with the 
Notification 
"Formulation and 
Publication of 
Risk Management 
Plans" dated 18 
March 2022
FINAL
08
February
2022
N/A
N/A
N/A
5. MILESTONES
Milestone
Planned date
Start of investigation period
February 2022
Start of data collection (registration date of the first 
subject)
31 March 2022
End of investigation period
April 2024
End of data collection (release date of the database)
November 2024
Interim report
28 September 2022
Final study report
October 2025

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6. RATIONALE AND BACKGROUND
PAXLOVID® PACK (generic name: nirmatrelvir tablets and ritonavir tablets) (hereinafter, 
this drug) is a combination of nirmatrelvir, an inhibitor of SARS-CoV-2 3CL protease, and 
ritonavir, a potent inhibitor of CYP3A4. The combination of the 2 drugs will maintain 
exposure to nirmatrelvir to inhibit viral replication throughout the treatment period. The 
marketing authorization of this drug was obtained in February 2022 in Japan for the 
indication of “Disease caused by SARS-CoV-2 infection (COVID-19).”
The objective of the “PAXLOVID® PACK General Investigation” (hereinafter, this study) is 
to assess the safety and effectiveness of this drug under post-marketing actual status of use.
This study shall be conducted in strict compliance with the “MHLW Ordinance on the 
Standard for Post-Marketing Studies and Clinical Trials of Medical Products” (MHLW 
Ordinance No. 171, dated December 20, 2004) , the “Enforcement of the MHLW Ordinance 
on the Standard for Post-marketing Studies and Clinical Trials of Medical Products” (PFSB 
Notification No. 1220008, dated December 20, 2004), “MHLW Ordinance on the Standard 
for Post-marketing Safety Control of Medical Products, Quasi-medical Products, Cosmetics, 
Medical Devices and Regenerative Medical Products” (MHLW Ordinance No. 135, dated 
September 22, 2004), the “Enforcement of the MHLW Ordinance on the Standard for Post-
marketing Safety Control of Medical Products, Quasi-medical Products, Cosmetics, and 
Medical Devices, Regenerative Medical Products” (PFSB Notification No. 0812-4, dated 
August 12, 2014), “MHLW Ordinance to Partially Amend the MHLW Ordinance on the 
Standard for Post-marketing Studies and Clinical Trials of Medical Products” (MHLW 
Ordinance No. 116, dated October 26, 2017), and “Announcement of the MHLW Ordinance 
to Partially Amend the MHLW Ordinance on the Standard for Post-marketing Studies and 
Clinical Trials of Medical Products (Regarding the MHLW Ordinance on the Standard for 
Post-Marketing Studies and Clinical Trials of Medical Products)” (PSEHB Notification No. 
1026-1, dated October 26, 2017).
7. RESEARCH QUESTION AND OBJECTIVES
The objective of this study is to assess the safety and effectiveness of this drug under post-
marketing actual status of use in patients receiving this drug.
7.1. Safety specifications
Important Identified Risks: Toxic epidermal necrolysis/oculomucocutaneous syndrome,
hepatic function disorder and anaphylaxis
Important Potential Risks: Hyperglycemia/diabetes mellitus and bleeding tendencies

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8. RESEARCH METHODS
8.1. Study design
This study is an open-label, multi-center, one arm prospective observational cohort study of 
patients receiving this drug. The investigators complete the CRF based on the information 
extracted from the medical record created in daily medical practice. 
8.2. Setting
Patients who satisfy all of the registration criteria are subject to this study.
8.2.1. Registration criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in this 
study:
Patients who receive this drug for the first time.
In principle, data will be collected prospectively. However, in order to collect data at an early 
stage after approval as much as possible, patients who started to receive this drug before 
conclusion of the contract may be enrolled in this study.
Refer to the latest package insert of this drug for “indications” and “dosage and 
administration” when this drug is administered.
[Indications]
Disease caused by SARS-CoV-2 infection (COVID-19)
[Dosage and administration]
The usual dosage in adults and pediatric patients (≥12 years of age weighting ≥40 kg) is 300
mg of nirmatrelvir and 100 mg of ritonavir all taken together orally twice daily for 5 days.
8.2.2. Exclusion criteria
There are no exclusion criteria for this study.
8.2.3. Study sites
Plan to conduct this study at 400 sites including the Department of Infectious Diseases, 
Department of Internal Medicine, etc.
8.2.3.1. Site requirements
Sites where patients can be followed up at the time of the site visit or by telephone, home 
visit, etc. after administration of this drug.

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8.2.4. Planned study period
The planned period covered by this study is as follows.
Investigation period: February 2022 to April 2024 (from the start of the registration period to 
the completion of the observation period of the last patient.)
Registration period: February 2022 to February 2024
The registration is terminated if the target number of the patients has been collected, even 
before the end of the registration period.
8.2.5. Study procedures
8.2.5.1. Study method
Continuous registration system: This study will be conducted with continuous registration 
system that patients who meet the registration criteria of this study will be registered 
sequentially until data are collected on a target number of patients for each investigation 
sites.
8.2.5.2. Request for cooperation in the study and contract
1. The site staff will explain the outline of this study to the physicians who are registered at 
PAXLOVID® PACK Registration Center and plan to use this drug.
2. If the site is selected as a study site, the site staff will conclude a contract for this study 
with the site.
8.2.6. Observation period
From the start date of administration to 28 days after the completion of administration (The 
day after the completion of administration is Day 1.)
8.3. Variables
This study will be conducted according to the following schedule of observation.

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Table 1.
Variables and schedule of observation
Variable
Registration 
form
CRF
Until 28 days after the 
completion of 
administration of this 
drug
ID number

*
Gender

*
Birth year and month/age

*
Eligibility

Start date of treatment with this drug

*
Height/body weight

History of smoking

Presence/absence of symptoms of the target disease, 
severity, and date of onset

Presence/absence of liver functional impairment and 
renal functional impairment, severity

Disease history

Prior medications for infections caused by SARS-CoV-2

History of SARS-CoV-2 vaccination

Presence/absence of pregnancy (only for women)

Presence/absence of findings of pneumonia attributable 
to infections caused by SARS-CoV-2 at the start of 
administration

Hospitalization status

Targeted drug use record

Concomitant therapy (Drug therapy/ Non-drug therapy)

Tests (virus/vital signs)

End-of-study/Discontinuation record (reason)

Effectiveness evaluation

Adverse events

Informed consent for publication of results

* Some elements in the Registration Form are automatically reflected in the CRF. The investigators 
should check and update the CRF as needed.
8.3.1. Patient characteristics
1. Enter the information at the start of administration of this drug into the registration form

ID number

Gender

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
Birth year and month/age (if birth year and month cannot be disclosed, age at the start 
of administration of this drug)

Start date of treatment with this drug

Eligibility
2. The following will be recorded in CRF at the start of administration of this drug:
(ID number, gender, and birth year and month/age in the Registration Form are automatically 
reflected in the CRF. The investigators should check and update the CRF as needed.

ID number

Gender

Birth year and month/age

Height (cm)

Weight (kg)

History of smoking

Presence/absence of symptoms of the target disease (disease for which this drug is 
used), severity, and date of onset 
The presence/absence of symptoms will be judged based on the clinical symptoms 
related to infections caused by SARS-CoV-2, including but not limited to the 
symptoms shown below.
Cough, shortness of breath or dyspnea, feeling hot, chills or shivering, fatigue 
(decreased energy or feeling tired), muscle pain or body pain, diarrhea (loose or 
watery stools), nausea (queasy), vomiting, headache, sore throat, stuffy or runny 
nose, dysosmia, dysgeusia, and findings of pneumonia
Severity should follow the severity classification in the “Clinical Practice Guidance 
for New Coronavirus Infection COVID-19” (see Table 2). 

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Table 2.
Severity classification
Severity 
Oxygen saturation 
Clinical status
Mild
SpO2≥96%
No respiratory symptoms, or cough alone 
with no dyspnea
No finding of pneumonia in either case
Moderate I
No respiratory failure
93%<SpO2<96%
Dyspnea, pneumonia findings
Moderate II 
Respiratory failure 
present
SpO2≤93%
Oxygen required
Severe
Admitted to ICU or requiring mechanical 
ventilation
Note
• It is desirable to measure SpO2 and objectively judge the state of oxygenation.
• In order to confirm the presence/absence of pneumonia, it is desirable to take measures 
against nosocomial infection and take chest CT scans to the extent possible.
• If there is a difference in severity between oxygen saturation and the clinical status, the 
higher severity should be assigned.
Excerpted from the Clinical Practice Guidance for New Coronavirus Infection COVID-19 
Version 6.2 (27 January 2022)

Presence/absence of liver impairment/renal impairment*, severity
*Liver impairment/renal impairment are not transient laboratory abnormalities but 
represent events that require clinical consideration and follow-up.
Reference
[Severity of hepatic impairment: Child-Pugh classification]
1 point
2 points
3 points
Hepatic encephalopathy
None
Mild (I/II)
Coma (III or 
higher)
Ascites
None
Mild 
Moderate or 
higher
Serum albumin level
>3.5 g/dL
2.8 to 3.5 g/dL
<2.8 g/dL
Prothrombin time
>70%
40% to 70%
<40%
Serum total bilirubin
<2.0 mg/dL
2.0 to 3.0 mg/dL
>3.0 mg/dL
A (mild), 5 to 6 points; B (moderate), 7 to 9 points; C (severe), 10 to 15 points

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[Severity of renal impairment]
Severe: eGFR [mL/min/1.73 m2] < 30
Moderate: 30 ≤ eGFR [mL/min/1.73 m2] < 60
Mild: 60 ≤ eGFR [mL/min/1.73 m2] < 90

Clinical history (past history and concurrent illness)
Enter complications that are risk factors for increasing severity.

Prior medications for infections caused by SARS-CoV-2 (within 1 month prior to the 
start of administration of this drug)

Drug name

Period of administration

Reason for discontinuation

History of SARS-CoV-2 vaccination (date of vaccination and name of vaccine)
8.3.2. Presence/absence of pregnancy (only for women)
The presence/absence of pregnancy from the start date of administration to the end of the 
observation period should be recorded.
8.3.3. Presence/absence of findings of pneumonia attributable to infections caused by 
SARS-CoV-2 at the start of administration
The presence/absence of findings of pneumonia attributable to infections caused by SARS-
CoV-2 before the start of administration (including the start date of administration) should be 
recorded.
1.
Date of evaluation
2.
Presence/absence of findings of pneumonia
8.3.4. Hospitalization status
Regarding the status of hospitalization during the observation period, the following 
information should be recorded.
1.
Presence/absence of hospitalization during the observation period
2.
Date of admission (reason for admission)/date of discharge

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8.3.5. Targeted drug use record
Regarding the status of use of this drug during the observation period, the following 
information should be recorded.
1. Dose per administration
2. Number of doses per day
3. Period of administration
4. Reason for change/interruption
5. Reason for discontinuation of administration (adverse events, other)
8.3.6. Concomitant therapy
8.3.6.1. Drug therapy
For all drugs used during the observation period, the following information should be 
recorded. If an adverse event is noted, the drugs used during the period from the start date of 
administration to the onset of the adverse event and medications used for treatment of the 
adverse event should also be recorded.
1. Drug name (product name)
2. Route of administration
3. Period of administration
4. Reasons for administration (infections caused by SARS-CoV-2, complications, adverse 
events, other)
8.3.6.2. Non-drug therapy
Regarding non-drug therapy for infections caused by SARS-CoV-2 performed during the 
observation period, the following information should be recorded. If an adverse event is 
observed, non-drug therapy used for the treatment of the adverse event should also be 
recorded.
1. The name of the therapy (oxygen administration, etc.)
2. Period of the therapy
3. Reason for the therapy (infections caused by SARS-CoV-2, adverse events, other)

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8.3.7. Tests/clinical laboratory tests
8.3.7.1. SARS-CoV-2 viral test
Results of tests performed before administration (including the start date of administration) 
and during observation period should be recorded.
1.
Date of tests
2.
Sampling site
3.
Test method (PCR/antigen test)
4.
Results (viral load, etc.)
5.
Type of variant of virus (wild type, Beta variant, Gamma variant, Delta variant, Omicron 
variant, etc.)
8.3.7.2. Vital signs
Results of tests performed before administration (including the start date of administration) 
and during observation period should be recorded.
1.
Date of tests
2.
Items of tests
Body temperature and percutaneous arterial oxygen saturation (SpO2)
8.3.8. End-of-study / Discontinuation record
The end date of the observation period (date of medical examination on or after Day 28 after 
the completion of administration) should be recorded. If the patient cannot be followed up 
until Day 28 after the completion of administration (including Day 28), record date of 
discontinuation and select only one of the following items that corresponds to the primary 
reason. If the primary reason corresponds to patient death, necessary information should be 
recorded in the adverse event field.
1.
End date of the observation period (date of examination on or after Day 28 after the 
completion of administration or date of discontinuation)
2.
Status at the end
Completed
Symptoms improved
Death

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Transferred to other hospital
Lost to follow-up
Other
However, if the patient does not return for follow-up visit after the start of administration 
(including confirmation by telephone, etc.), the information should be recorded in the “lost to 
follow-up.”
8.3.9. Effectiveness evaluation (severity)
The presence/absence of worsening of the severity of infections caused by SARS-CoV-2 
after administration of this drug during the observation period (until Day 28 after the 
completion of administration [including Day 28]), highest severity, and presence/absence and 
severity of symptoms on the end date of the observation period (date of medical examination 
on or after Day 28 after the completion of administration) should be entered. For cases 
discontinuing observation in less than 28 days after the completion of administration, the 
highest severity by that point and the severity as of the date of discontinuation of the 
observation period should be recorded (see Table 2 for severity).
1. Worsening of severity after administration
Presence/absence of worsening of symptoms
Date of highest severity
Highest severity
2. Severity on the end date of the observation period
Date of evaluation
Presence/absence of symptoms of infections caused by SARS-CoV-2
Severity
8.3.10. Adverse events
Occurrence of adverse events from the start date of administration of this drug to the end date 
of the observation period should be confirmed and the following information should be 
recorded.
Also, further investigation should be separately conducted, if deemed necessary by Sponsor 
for patients who experienced a serious adverse reaction, an unexpected adverse reaction or 
other adverse reactions not listed in the package insert.

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
Presence/absence of adverse event

Name of adverse event

Date of occurrence

Intervention

Seriousness

Outcome

Causal relationship to this drug
If the adverse event is associated with abnormal laboratory values, i.e., clinical laboratory 
tests, the following information should also be recorded.

Date of tests

Name of laboratory test

Site reference value

Site unit

Test results
8.4. Data sources 
In this study, the investigators transcribe the necessary information from the medical record 
under daily medical practice in accordance with the full protocol.
8.5. Study size
8.5.1. Planned sample size
Target sample size: 3000 subjects (for safety analysis set)
8.5.2. Rationale for sample size
The incidence of adverse reactions to this drug in the phase 2/3 study (Study 4671005) was 
7.8%. Assuming that the incidence of adverse reactions under the actual status of use in 
Japan is the same, adverse reactions will be detected in at least 214 patients with a 
probability of 90% with a sample size of 3000 patients. In order to detect, with a probability 
of 95%, at least 1 patient with an unknown adverse reaction occurring at a frequency of 0.1% 
or more, 3000 patients are required.

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8.6. Data management
8.6.1. Case report forms (CRFs)/ Electronic data record
As used in this full protocol, the term CRF should be understood to refer to an electronic data 
record, depending on the data collection method used in this study.
A CRF is required and should be completed for each included patient. The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. The investigator shall ensure that the 
CRFs are securely stored at the study site in encrypted electronic form and will be password 
protected or secured in a locked room to prevent access by unauthorized third parties.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete,
consistent, legible, timely (contemporaneous), enduring, and available when required. The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed (or stamped “correction seal”), and explained (if 
necessary) and should not obscure the original entry.
The source documents are the hospital or the physician’s chart. In these cases, data collected 
on the CRFs must match those charts.
8.6.2. Record retention
The records related to this study should be retained at the study site until the End of Study 
Letter by Pfizer is received or during the period defined by the study site, whichever is 
longer.
8.6.3. Data collection method (EDC)
The data for this study will be collected and confirmed by using the electronic system on the 
internet designed for collecting post-marketing survey data (Electronic Data Capture, EDC).
8.6.4. Patient registration (EDC)
The investigator will enter information on the patient registration screen of EDC (the 
registration form) and save the data. Patient registration will be performed immediately after 
the first administration of this drug.
If information in the registration form requires confirmation, the investigator may be 
requested to perform follow-up survey and respond to the query. Registration will be fixed 
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In this study, patients after the start of supply of this drug will also be registered regardless of 
the date of contract conclusion.
8.6.5. Points to consider for completion, revision, and submission of case report form 
(EDC)
8.6.5.1. Data entry
The investigator should confirm the survey items and enter the data into EDC based on 
medical records.
8.6.5.2. Data revision
Upon receiving query from Sponsor on the contents of the CRF (follow-up survey), the 
investigator will again confirm the contents of medical records, and as required, correct 
relevant sections and save the data.
8.6.5.3. Submission
After data entry and revision are completed, CRFs should be signed electrically by the 
investigator following confirmation of entry and follow-up survey.
8.7. Data analysis
1. Definition of analysis set
The safety analysis set (SAS) consists of a full analysis set (FAS) that is as closer as 
possible to all patients who received this drug. Three effectiveness analysis sets are 
defined as follows.

Effectiveness Analysis Set 1: A population of patients in which effectiveness can be 
evaluated among patients in which this drug was administered

Effectiveness Analysis Set 2: A population of patients in Effectiveness Analysis Set 1 
who are outpatients at the start of administration of this drug

Effectiveness Analysis Set 3: A population of patients in Effectiveness Analysis Set 2 
who have risk factors for increased severity at the start of administration of this drug
2. Method of analysis

Analysis for safety evaluation
Events possibly related to this drug are considered as adverse reactions. The number of 
patients with adverse reactions and the proportion [(%): number of patients with adverse 
reactions / number of patients included in the safety analysis set] will be calculated.

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
Analysis for effectiveness evaluation
For Effectiveness Analysis Sets 1, 2, and 3, the number of patients by highest severity 
after administration of this drug and the number of patients by severity on the end date of 
the observation period will be tabulated.
For Effectiveness Analysis Set 1, the number of patients who died for any reason during 
the period from the start date of administration to Day 28 will be tabulated.
For Effectiveness Analysis Sets 2 and 3, the number of patients who have been 
hospitalized for treatment of infections caused by SARS-CoV-2 or died for any cause 
during the period from the start date of administration to Day 28 will be tabulated. The 
number of respective patients will also be tabulated. The number of these patients will 
also be tabulated in the subgroup of patients with no history of treatment with drugs for 
infections caused by SARS-CoV-2.
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in the SAP, which will be dated and retained by Pfizer. The SAP may 
modify the plans outlined in the full protocol; however, any significant modifications of 
definitions or analyses of endpoints will also be reflected in a protocol amendment.
8.8. Quality control
Prior to conducting the study, the site staff will explain to the investigator about the contents 
of the protocol, etc. and ask the investigator for completion of a case report form based on 
medical records.
8.9. Limitations of the research methods
There may be potential limitations in this study:
1. Since no control group is included in the study, there is a limitation in determining 
whether or not a risk of developing adverse events and adverse reactions increases with 
administration of this drug.
2. Due consideration may not be given to confounding factors due to insufficient 
background information collected.
3. Since this study collects the information described in medical records, specified data may 
not be collected or may be missing.
8.10. Other necessary matters
Not applicable

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9. PROTECTION OF HUMAN SUBJECTS
9.1. Patient information
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of patient personal data. Such 
measures will include omitting patient names or other directly identifiable data in any 
reports, publications, or other disclosures, except where required by applicable laws. The 
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 shall be responsible for determining 
whether a personal data breach has in fact occurred and, if so, providing breach notifications 
as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer and other authorized 
parties, patient names will be removed and will be replaced by a single, specific, numerical 
code, based on a numbering system defined by Pfizer. All other identifiable data transferred 
to Pfizer or other authorized parties will be identified by this single, patient-specific code. 
The investigator site will maintain a confidential list of patients who participated in the study, 
linking each patient’s numerical code to his or her actual identity. In case of data transfer, 
Pfizer will maintain high standards of confidentiality and protection of patients’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
9.2. Patient consent
As this study does not involve data subject to privacy laws according to applicable legal 
requirements, or it is an information provision based on the law (even though that involve 
data subject to privacy laws according to applicable legal requirements), obtaining informed 
consent from patients by Pfizer is not required with regard to the personal information 
provision from the study site to Pfizer. Also, because the report of information or results 
collected in this study to the local regulatory authority or healthcare providers by Pfizer as 
needed is an information provision based on the law, obtaining informed consent from 
patients by Pfizer is not required.
In this study, Pfizer will collect information that cannot identify specific patients from the 
institutions. The results of this study, which are prepared not to identify specific patients, 
may be reported to Pfizer Inc., which is the corporate parent of the sponsor of this study, or 
group companies, or regulatory authorities in other countries, as needed, or published it as a 
presentation at academic conferences or manuscript for the purpose of providing proper use 
information for this drug. If these information falls under personal information of the 
Personal Information Protection Act, these actions may not be based on the laws or 
regulations, and therefore, may correspond to provision to the third party and using the 

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information for purposes other than business that require consent from the patient. Therefore, 
the study institutions will obtain written or verbal consent from the patients to be included in 
this study so that Pfizer can use the results of this study to report to Pfizer Inc., group 
companies or regulatory authorities in other countries, or to present it at academic 
conferences or publish manuscript, etc. Whether consent is obtained from patients or not is 
described in the CRF. The original of the written informed consent form should be retained 
by the study investigator. 
In general, the investigator must obtain consent from a patient personally. However, if the 
investigator determines that a patient’s decisional capacity is so limited that he or she cannot 
reasonably be consulted or he or she is a minor, consent is obtained from legally acceptable 
representative or parent(s). In this case, every effort should be made to obtain the patient’s 
assent as far as possible after obtaining consent from legally acceptable representative or 
parent(s) if a minor. If the study patient does not provide his or her own consent, the source 
documents must record the relationship of the person signing the consent and the patient 
(e.g., parent(s), spouse). If a minor registered in the study reaches adulthood during the study, 
the consent will be reacquired as far as possible from the patient at the time of adulthood 
according to Japanese law.
At the time of obtaining informed consent, the investigator must use informed consent form 
and other materials and ensure that each study patient[, or his or her legally acceptable 
representative, or parent(s) if a minor,] is fully informed about the information provided to 
Pfizer and the objectives of use and possible risks associated with consent.
9.3. Institutional review board (IRB)/Independent ethics committee (IEC)
In this study, review by the Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) is not required.
9.4. Ethical conduct of the study
This study will be conducted in compliance with the MHLW Ordinances in the section 6. 
RATIONALE AND BACKGROUND. Also, the study will be conducted in accordance with 
legal and regulatory requirements, as well as with scientific purpose, value and rigor.
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS
10.1. Requirements for recording and reporting
The table below summarizes the requirements for recording safety events on the CRFs and 
for reporting safety events on the non-interventional study (NIS) adverse event monitoring 
(AEM) Report Form to Pfizer Safety. These requirements are delineated for three types of 
events: (1) serious adverse events (SAEs); (2) non-serious AEs (as applicable); and (3) 
scenarios involving drug exposure, including exposure during pregnancy, exposure during 

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breast feeding, medication error, overdose, misuse, extravasation, lack of efficacy, and 
occupational exposure. These events are defined in the section “Definitions of safety events.”  
Safety event
Recorded on the CRF
Reported on the NIS 
AEM Report Form to 
Pfizer Safety within 24 
hours of awareness
SAE
All
All
Non-serious AE
All
None
Scenarios involving exposure to a 
drug under study, including 
exposure during pregnancy, 
exposure during breast feeding, 
medication error, overdose, 
misuse, extravasation, lack of 
efficacy, and occupational 
exposure
All (regardless of whether 
associated with an AE), except 
occupational exposure
All (regardless of 
whether associated with 
an AE)
Note: Any associated AE 
is reported together with 
the exposure scenario.
For each AE, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a SAE 
(refer to section “Serious Adverse Events” below).
Safety events listed in the table above must be reported to Pfizer within 24 hours of 
awareness of the event by the investigator regardless of whether the event is determined 
by the investigator to be related to this drug. In particular, if the SAE is fatal or life-
threatening, notification to Pfizer must be made immediately, irrespective of the extent of 
available event information. This timeframe also applies to additional new (follow-up) 
information on previously forwarded safety event reports. In the rare situation that the 
investigator does not become immediately aware of the occurrence of a safety event, the 
investigator must report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the events.
For safety events that are considered serious or that are identified in the far-right column of 
the table above that are reportable to Pfizer within 24 hours of awareness, the investigator is
obligated to pursue and to provide any additional information to Pfizer in accordance with 
this 24-hour timeframe. In addition, an investigator may be requested by Pfizer to obtain 
specific follow-up information in an expedited fashion. This information is more detailed 
than that recorded on the CRF. In general, this will include a description of the AE 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 patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative.

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10.2. Reporting period
For each patient, the safety event reporting period begins at the time of the patient’s first dose 
of this drug and lasts through the end of the observation period of the study, which must 
include at least 28 calendar days following the last administration of a drug under study; a 
report must be submitted to Pfizer Safety (or its designated representative) for any of the 
types of safety events listed in the table above occurring during this period. If a patient was 
administered a drug under study on the last day of the observation period, then the reporting 
period should be extended for 28 calendar days following the end of observation.
If the investigator becomes aware of a SAE occurring at any time after completion of the 
study and s/he considers the SAE to be related to this drug, the SAE also must be reported to 
Pfizer Safety.
10.3. Causality assessment
The investigator is required to assess and record the causal relationship. For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of 
each AE. For AEs with a causal relationship to this drug, follow-up by the investigator is 
required until the event and/or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment.  
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that this drug caused or contributed to an AE. If the investigator’s final 
determination of causality is “unknown” and s/he cannot determine whether this drug caused
the event, the safety event must be reported within 24 hours.  
If the investigator cannot determine the etiology of the event but s/he determines that this
drug did not cause the event, this should be clearly documented on the CRF and the NIS 
AEM Report Form. 
10.4. Definitions of safety events
Adverse events
An AE is any untoward medical occurrence in a patient administered a medicinal product. 
The event need not necessarily have a causal relationship with the product treatment or 
usage. Examples of AEs include but are not limited to:  

Abnormal test findings (see below for circumstances in which an abnormal test finding 
constitutes an AE);

Clinically significant signs and symptoms;

Changes in physical examination findings;

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
Hypersensitivity;

Progression/worsening of underlying disease;

Lack of efficacy;

Drug abuse;

Drug dependency.
Additionally, for medicinal products, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse;

Off-label use;

Drug interactions;

Extravasation;

Exposure during pregnancy;

Exposure during breast feeding;

Medication error;

Occupational exposure.
Abnormal test findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

Test result is associated with accompanying symptoms, and/or

Test result requires additional diagnostic testing or medical/surgical intervention, and/or

Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy, and/or

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
Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
Serious adverse events
A SAE is any untoward medical occurrence in a patient administered a medicinal or 
nutritional product (including pediatric formulas) at any dose that:

Results in death;

Is life-threatening;

Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute AEs);

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization. However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above, the important medical event should be reported as serious.
Examples of such events are 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.
Additionally, any suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious. The event may be suspected from 
clinical symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product. The terms “suspected transmission” and “transmission” are considered 
synonymous. These cases are considered unexpected and handled as serious expedited cases 
by pharmacovigilance (PV) personnel. Such cases are also considered for reporting as 
product defects, if appropriate.

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Hospitalization
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission. Admission also 
includes transfer within the hospital to an acute/intensive care unit (e.g., from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, an event leading to an emergency room visit should be assessed for medical
importance.
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. 
For example, the following reports of hospitalization without a medical AE are not to be 
reported.

Social admission (e.g., patient has no place to sleep)

Administrative admission (e.g., for yearly exam)

Optional admission not associated with a precipitating medical AE (e.g., for elective 
cosmetic surgery)

Hospitalization for observation without a medical AE

Admission for treatment of a pre-existing condition not associated with the development 
of a new AE or with a worsening of the pre-existing condition (e.g., for work-up of 
persistent pre-treatment lab abnormality)
Scenarios necessitating reporting to Pfizer Safety within 24 hours
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication 
error, overdose, misuse, extravasation, lack of efficacy, and occupational exposure are 
described below.
Exposure during pregnancy
An exposure during pregnancy (EDP) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed to (e.g., environmental) this drug, or the female becomes, or is found to be, 
pregnant after discontinuing and/or being exposed to this drug (maternal exposure).
An example of environmental exposure would be a case involving direct contact with a 
Pfizer product in a pregnant woman (e.g., a nurse reports that she is pregnant and has been 
exposed to chemotherapeutic products).

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2. A male has been exposed, either due to treatment or environmental exposure to this drug 
prior to or around the time of conception and/or is exposed during the partner pregnancy 
(paternal exposure).
For exposure during pregnancy in studies of pregnant women, data on the exposure to drug
during pregnancy, are not reportable unless associated with serious or non-serious adverse 
events.
As a general rule, prospective and retrospective exposure during pregnancy reports from any 
source are reportable irrespective of the presence of an associated AE and the procedures for 
SAE reporting should be followed, with the exception of those studies conducted in pregnant 
women (as described in above), for which data on the exposure are not reportable unless
associated with serious or non-serious adverse events.
If a study participant or study participant’s partner becomes, or is found to be, pregnant 
during the study participant’s treatment with this drug, this information must be submitted to 
Pfizer, irrespective of whether an AE has occurred using the NIS AEM Report Form and the 
EDP Supplemental Form.
In addition, the information regarding environmental exposure to this drug in a pregnant 
woman (e.g., a patient reports that she is pregnant and has been exposed to a cytotoxic 
product by inhalation or spillage) must be submitted using the NIS AEM Report Form and 
the EDP Supplemental Form. This must be done irrespective of whether an AE has occurred.
Information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy; in addition, follow-
up is conducted to obtain information on EDP outcome for all EDP reports with pregnancy
outcome unknown. A pregnancy is followed until completion or until pregnancy termination 
(e.g., induced abortion) and Pfizer is notified of the outcome. This information is provided as 
a follow up to the initial EDP report. In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth. In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (e.g., ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
procedures for reporting SAEs should be followed.
Additional information about pregnancy outcomes that are reported as SAEs follows:

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
Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs. In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure
to investigational product.
Additional information regarding the exposure during pregnancy may be requested. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (e.g., follow-up on 
preterm infants to identify developmental delays).
In the case of paternal exposure, the study participant will be provided with the Pregnant 
Partner Release of Information Form to deliver to his partner. It must be documented that the 
study participant was given this letter to provide to his partner.
Exposure during breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated AE. An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (e.g., vitamins) is administered in 
accord with authorized use. However, if the infant experiences an AE associated with such a 
drug’s administration, the AE is reported together with the exposure during breastfeeding.
Medication error
A medication error is any unintentional error in the prescribing, dispensing, or administration 
of a medicinal product that may cause or lead to inappropriate medication use or patient harm 
while in the control of the health care professional, patient, or consumer. Such events may be 
related to professional practice, health care products, procedures, and systems including: 
prescribing; order communication; product labeling, packaging, and nomenclature; 
compounding; dispensing; distribution; administration; education; monitoring; and use.  
Medication errors include:

Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or prescription 
on the part of the healthcare provider or the patient/consumer);

Confusion with regard to invented name (e.g., trade name, brand name).
The investigator must submit the following medication errors to Pfizer, irrespective of the 
presence of an associated AE/SAE:

Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE.

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
Medication errors that do not involve a patient directly (e.g., potential medication errors 
or near misses). When a medication error does not involve patient exposure to the 
product the following minimum criteria constitute a medication error report:

An identifiable reporter;

A suspect product;

The event medication error.
Overdose, Misuse, Extravasation
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product are 
reported to Pfizer by the investigator, irrespective of the presence of an associated AE/SAE.
Lack of Efficacy
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE or the indication for use of the Pfizer 
product.
Occupational Exposure
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the 
investigator, irrespective of the presence of an associated AE/SAE.
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
Information collected in this study will be used for reporting purposes to report Ministry of 
Health, Labour and Welfare (MHLW), Pharmaceuticals and Medical Devices Agency 
(PMDA), Pfizer Inc. which is the corporate parent of the sponsor of this study, and the group 
companies, or regulatory agency in other countries. Also, it will be used for submitting 
application of re-examination (including Periodic Safety Update Report), re-evaluation, 
preparation of material for proper use information of this drug, publications and activities for 
information provision. In addition, Pfizer may disclose the study results to provide 
information for proper use, as needed, on www.clinicaltrials.gov (ClinicalTrials.gov), as 
presentations at academic conferences, or as manuscripts, etc. 
Data obtained from the patients registered in this Study will be reported to the MHLW 
pursuant to the Pharmaceutical and Medical Device Act. In this case, the data may be 
publicly posted in MHLW’s “Pharmaceutical and Medical Device Safety Information” and 
“Pharmaceuticals and Medical Devices Information Website (http://www.info.pmda.go.jp)”
as a listing of patients, which will include the names of drugs, adverse reactions, gender, age 
(increment of 10 years), and other relevant information. Furthermore, data collected may also 
be disclosed if the MHLW is required to disclose such information in accordance with the 

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“Act on Access to Information Held by Administrative Organs” (Law No. 42 dated May 14, 
1999); provided that in no event will the names of physicians, medical institutions, and other 
personal information be subject to such disclosure, nor will it be posted or disclosed. 
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable 
Competent Authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of a Pfizer 
product, Pfizer should be informed immediately. 
12. NAME, AND ADDRESS OF CONTRACTOR AS WELL AS SCOPE OF WORK 
CONTRACTED

Company name: Pfizer R&D Japan
Address: 3-22-7, Yoyogi, Shibuya-ku, Tokyo
Scope of work contracted: Works related to planning of study, drafting of plan,
implementation of study, monitoring, etc.

Company name: Medidata Solutions
Address: 2-7-2, Marunouchi, Chiyoda-ku, Tokyo
Scope of work contracted: Establishment, operation and maintenance of the EDC system, 
etc.

Company name: A2 Healthcare Corporation
Address: 1-4-1, Koishikawa, Bunkyo-ku, Tokyo
Scope of work contracted: Registration operations, etc.

Company name: EPS Corporation
Address: 2-23 Shimomiyabicho, Shinjuku-ku, Tokyo
Scope of work contracted: Establishment of the EDC system, data management, 
statistical analysis, monitoring, etc.
13. ADDITIONAL MEASURES THAT MAY BE IMPLEMENTED BASED ON THE 
STUDY RESULTS AND CRITERIA FOR DETERMINATION OF THE INITIATION
Review the risk management plan including the following contents at the scheduled timing of 
milestones.
1. Review the necessity for changing the contents of risk minimization activities for the 
current safety specifications.
2. Review the necessity for changing the contents of this study plan including the presence 
or absence of new safety specifications (continuation of the study, implementation of 
additional study, etc.).

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3. Review the necessity for formulating risk minimization measures for new safety 
specifications.
14. SCHEDULED TIMING OF MILESTONES AND THEIR RATIONALES FOR
EVALUATION OF STUDY IMPLEMENTATION STATUS AND RESULTS AND 
REPORTING TO THE PMDA

At the time of the report at 6 months after the start of the study or when the number of 
study subjects exceeds 1000, whichever comes first

At the time of submission of periodic safety reports

At the time of the final report
To comprehensively examine safety information, etc.
15. OTHER NECESSARY MATTERS
1. Amendment of the full protocol
Based on new findings obtained according to the progress of this study, the necessity of 
amendment of the full protocol will be examined and the full protocol will be amended as 
necessary. Also, the need for amendment of the full protocol will be examined and the full 
protocol will be amended when the partial change in the dosage and administration or 
indication is approved during the reexamination period (except when the reexamination period 
is newly designated), etc.
2. Actions to be taken for any problem or issue
Revision of the package insert and conduct of a new Post-marketing surveillance or new
Post-marketing Clinical Trial should be considered for the following cases: any serious and 
unknown adverse reaction is suggested; a significant increase in the frequency of adverse 
reactions; any effectiveness or safety concern compared to pre-approval; rare adverse 
reaction is suggested.
16. CONTACT INFORMATION
16.1. Contact information for inquiries about the study
Name
PMS Affairs, Pfizer R&D Japan
Address
Shinjuku Bunka Quint Building, 3-22-7, Yoyogi, Shibuya-ku, Tokyo 151-8589
FAX
03-5309-9186
E-mail address
PAX_DRPMS@pfizer.com

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16.2. Contact information for inquiries about the EDC system (In the case of study 
using EDC)
Name
Medidata Helpdesk
Business Hours
Weekdays: 9:00 - 20:00 (excluding Saturday/Sunday, Holidays and New Year 
Holidays)
TEL
(Dedicated dial for Pfizer)
E-mail address
japanhelpdesk@mdsol.com
17. REFERENCES
Clinical Practice Guidance for New Coronavirus Infection COVID-19 Version 6.2 (27 
January 2022)
18. LIST OF TABLES

Page12. Table 1. Variables and schedule of observation

Page14.  Table 2 Severity classification
19. LIST OF FIGURES
Not applicable
ATTACHMENT 1. TABLE OF CONTENTS OF INDEPENDENT DOCUMENTS
Not applicable
ATTACHMENT 2. ADDITIONAL INFORMATION
Not applicable
PPD