Conditions: Acute Migraine
Keywords: Migraine
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 241
Healthy volunteers: no

Brief summary:
This trial is to evaluate the long-term safety and tolerability of Rimegepant 75mg ODT in Chinese subjects with migraine

Detailed description:

Arms:
arm 1: One rimegepant (BHV3000) 75mg orally disintegrating tablet (up to 1 tablet per day)

Interventions: intervention 1: Rimegepant 75mg Orally Disintegrating Tablets (ODT)
Intervention descriptions: intervention 1: One rimegepant (BHV3000) 75mg orally disintegrating tablet (up to 1 tablet per day) at the time of their migraine attack

Protocol document:
Prot_000.pdf: 
Rimegepant PF-07899801 (Formerly BHV3000)
Protocol BHV3000-318 (Pfizer C4951018)
Protocol Amendment 4 / Version 5 18 August 2023
PFIZER CONFIDENTIAL
Page 1 / 83
AN INTERVENTIONAL, PHASE 3, SINGLE ARM, OPEN LABEL STUDY TO 
INVESTIGATE LONG-TERM SAFETY OF RIMEGEPANT ORALLY 
DISINTEGRATING TABLETS FOR THE ACUTE TREATMENT OF 
MIGRAINE IN CHINESE PARTICIPANTS
Study Intervention Number: 
Rimegepant PF-07899801 (BHV3000)
IND Number: 
N/A
EudraCT Number: 
N/A
ClinicalTrials.gov ID:
NCT05371652
Protocol Number:
BHV3000-318 (C4951018)
Version Date:
18 August 2023
Sponsor Legal Address:
Pfizer Inc.
66 Hudson Boulevard East
New York, NY 10001
Brief Title:
A study to learn about the long-term safety of rimegepant for the acute treatment of migraine 
in Chinese 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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DOCUMENT HISTORY
Document 
Version Date
Amendment 4 – Version 5.0
18 August 2023
Amendment 3 – Version 4.0
28 June 2022
Amendment 2 – Version 3.0
07 Febury 2022
Amendment 1 – Version 2.0
05 November 2021
Original protocol – Version 1.0
27 August 2021
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any protocol administrative change 
letter(s).
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
Description of Change
Brief Rationale
Section #
Substantial Modification(s)
Referenced study number 
BHV3000-318 to Pfizer 
C4951018 and compound name 
BHV-3000 to PF-07899801 to 
reflect identification changes by 
sponsor.
Reflected change in sponsorship 
protocol and compound 
identification numbers
Title page
Headers 
Section 1.1
Section 2 
Section 7.1.1 
Sponsor name changed.
Reflected transfer of sponsorship 
from BioShin (Shanghai) 
Consulting Services Co., Ltd to 
Pfizer Inc.
Throughout the 
document
Updated benefit risk background 
information and added benefit 
risk assessment 
Updated benefit risk information. 
Capsuled the content of 
Pharmarceutical Development 
Background, and removed the 
detailed clinical study data which 
is referred to IB.
Section 2.2 
Pharmarceutical 
Development 
Background
Section 2.5 
Benefit Risk 
Assessment
Updated contraception 
requirement for WOCBP and 
removed contraception 
requirement for males and added 
sections for “Women of 
Childbearing Potential” and 
“Pregnancy”.
Aligned with Pfizer standard and 
processes.
Section 5.2 
Inclusion Criteria 
#3b
Section 5.6 
Contraception
Section 12.3 
Appendix 3 –
Contraceptive and 
Barrier Guidance
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Description of Change
Brief Rationale
Section #
Former Section 
5.6 Women of 
Childbearing 
PotentialRemoved
Updated requirement for 
duration of contraception use 
after last dose of study drug 
Aligned with Pfizer standard and 
processes
Section 5.3 
Exclusion Criteria 
#4a
Non-substantial Modification(s)
Modification of the wording of 
primary endpoints
1. Removed “physical 
examination” because physical 
examination abnormalities would 
be captured as AEs or medical 
history.
2. Modified “ECG, vital 
signs/physical measurements and 
clinical laboratory test data” to 
“ECG, vital signs/physical 
measurements and clinical 
laboratory test abnormalities”.
Section 1
Section 3.2.1
Section 10.5.2
Clarification of descriptive 
summary method and addition of 
the 95% confidence interval (CI) 
method for the secondary 
endpoint.  
1. Clarified that values, changes 
and percent changes from 
Observation Period would be 
descriptively summarized by total 
and severity. 
2. Added that two-sided 95% CI 
would be derived based on normal 
distribution.
Section 10.5.3
Re-organization of protocol 
summary
Sponsor-required template.
Section 1
Clarified that this amendment 
incorporates all revisions to date, 
including amendments made at 
the request of country health 
authorities and IRBs/ECs and 
any PACL.
Aligned with Pfizer protocol 
template.
Title page
Modification of exclusion 
criterion 2b
Added cerebrovascular disease in 
the exclusionary condition to keep 
consistent throughout the 
paragraph.
Section 1
Section 5.3
Clarification of secondary 
endpoint
Clarified the language for 
secondary endpoint by specifying 
that it was change from 
Observation Period and would be 
broken down by total and severity 
Section 1
Section 3.2.2
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Description of Change
Brief Rationale
Section #
to make it more accurate and 
clearer.
Modification of exploratory 
endpoints
Modification on language of 
exploratory endpoints by 
specifying the percentage for 
Satisfaction with Medication (SM) 
and Clinical Global Impression-
change (CGI-c) and total score for 
Migraine Disability Assessment 
(MIDAS) to make them more 
accurate and clearer.
Section 1
Section 3.2.3
Combined the sections of Study 
Objectives and Endpoints
Aligned with Pfizer protocol 
template
Section 3
Former section 4 
removed
Added one pregnancy test at 
each Phone Visit
Added one pregnancy test (urine) 
at each Phone Visit (Week 20, 24, 
32, 36, 44 and 48) to ensure the 
monthly pregnancy test for each 
WOCBP.
Section 4.3.2
Section 5.6
Section 6.1.4.2
Modified the description of 
study drug dispense.
Modified the description of  study 
drug dispense to keep it consistent 
with footnote 8 of SOA.
Section 4.3.2
Modified the description of End 
of Trial 
To clarify the definition of early 
termination and criteria of 
permenant termination. 
Section 4.3.6
Definition of wash-out period of 
prophylactic migraine 
medication
Definition of wash-out period of 
prophylactic migraine medication 
prior to Screening Visit.
Section 5.2 2f
Section 5.5
Changed term “non-migraine” to 
“non-headache”, and term “acute 
migraine” to “acute headache”. 
Clarified to include broader 
definition of headache which 
includes non-migraine and 
migraine headache 
Section 5.4 
Prohibited 
Concomitant 
Medications 
Modified the description of 
efficacy assessment 
Removed the sentence of analysis 
method, and added some texts 
about how daily migraine will be 
assessed via eDiary by total and 
severity.
Section 6.2.1
Change in study drug storage 
condition.
Removed humidity from study 
drug storage conditions.
Section 7.1.2
Clarified study drug destruction 
Updated destination for study drug 
destruction 
Section 7.5 
Change in follow up of 
AEs/SAEs
Each event should be followed.
Section 8.6
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Description of Change
Brief Rationale
Section #
Definition of mapping rule of 
AE causality
Definition of mapping rule of AE 
causality between the five-point 
method and binary method 
following the guideline of Health 
Authority.
Section 8.9
Change in SAE reporting 
destination and electronic 
reporting system.
Incorporation of non-substantial 
changes described in previous 
PACL dated 28 Apr 2023.
Section 8.10 
Section 8.11
Added Pfizer standard safety 
language for environmental 
exposure, exposure during 
pregnancy, exposure during 
breastfeeding, occupational 
exposure
Aligned with Pfizer protocol 
template
Section 8.11 
Deletion of texts about statistical 
test 
The texts “all statistical tests will 
use a test with α=0.05” was 
deleted as no hypothesis was 
planned in this study.
Section 10.1
Clarification of sample size 
rationale
The rationales for study sample 
size of 233 and interim analysis 
with 175 participants are added.
Section 10.2
Section 10.3
Modification to the analysis sets
The per protocol set was removed 
and efficacy analysis set was 
added
Section 10.4.2
Clarification of safety analysis 
method
1. Removed the analysis which 
says “Changes in safety 
parameters such as laboratory tests 
and physical examination from 
baseline will be summarized using 
cross-tabulations before and after 
treatment.”
2. Added the analyses for liver 
function test, and abnormality 
summaries for ECG, vital signs, 
and laboratory test.  
Section 10.5.2
Modification of analyses 
methods for the secondary 
endpoints
Added the sentence of analysis 
method.
Section 10.5.3
Modification of analyses 
methods for the exploratory 
endpoints
1. Removed the sentence 
mentioning appropriate descriptive 
statistics.
2. Clarified that the normal 
distribution would be used to 
Section 10.5.4
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Description of Change
Brief Rationale
Section #
construct the 95% CIs for 
continuous endpoints.
3. Added exact Clopper-Pearson 
method to construct the 95% CIs 
for categorical endpoints. 
Reorganized the section numbers 
of Supporting Documentation 
And Operational Considerations
Aligned with Pfizer protocol 
template.
Former Section 
11-Section 17
Added Pfizer standard text for 
Data Protection.
Aligned with Pfizer protocol 
template.
Section 11.2.3
Added Pfizer standard text for 
Dissemination of Clinical Study 
Data. 
Aligned with Pfizer protocol 
template.
Section 11.4 
Added definition of Sponsor's 
Medically Qualified Individual.
Aligned with Pfizer protocol 
template.
Section 11.4
Removed the contact 
information of sponsor.
Removed the redundant 
information.
Former Section 
17.5.1
Addition of Brief Title 
As required by Sponsor Template 
and in scope of posting on 
clinicaltrials.gov, 
pfizerclinicaltrials.com and on 
advocacy and other websites that 
potential participants may visit as 
they consider clinical trial 
participation. 
Page 1
Update of List of Abbreviations
Editorial
List of 
Abbreviations
Update of references
Editorial
Section 13
Removed PI declaration page  
Aligned with Pfizer protocol 
template 
Former PI 
declaration page 
removed.
Removed protocol approval 
form
This page is not required by the 
relevant Sponsor’s SOPs.
Former Protocol 
approval form
removed.
Updated document header and 
footer
Updated to align with Pfizer 
protocol template
Header and 
Footer
Administrative edits and 
correction of typos
Some administrative 
edits/clarifications were made and
typographical errors were
corrected.
Throughout the 
document.
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TABLE OF CONTENTS
DOCUMENT HISTORY...........................................................................................................2
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE......................................2
LIST OF TABLES...................................................................................................................11
LIST OF FIGURES .................................................................................................................11
LIST OF ABBREVIATIONS..................................................................................................12
1. PROTOCOL SUMMARY...................................................................................................16
1.1. Synopsis ..................................................................................................................16
1.2. Study Schematic......................................................................................................20
2. INTRODUCTION AND RATIONALE..............................................................................21
2.1. Therapeutic Area Background ................................................................................21
2.2. Pharmaceutical Development Background .............................................................21
2.3. Study Rationale .......................................................................................................22
2.3.1. Study Design Rationale ..............................................................................23
2.3.2. Dose Selection Rationale............................................................................23
2.4. Study Hypothesis.....................................................................................................23
2.5. Risk and Benefit Assessment ..................................................................................23
3. STUDY OBJECTIVES AND ENDPOINTS.......................................................................25
3.1. Study Objectives .....................................................................................................25
3.1.1. Primary Objectives .....................................................................................25
3.1.2. Secondary Objectives .................................................................................25
3.1.3. Exploratory Objectives ...............................................................................25
3.2. Study Endpoints ......................................................................................................25
3.2.1. Primary Endpoints ......................................................................................25
3.2.2. Secondary Endpoints ..................................................................................25
3.2.3. Exploratory Endpoints................................................................................26
4. STUDY PLAN.....................................................................................................................26
4.1. Overall Design and Duration...................................................................................26
4.2. Study Schematic......................................................................................................27
4.3. Schedule of Activities .............................................................................................28
4.3.1. Screening Visit, Observation Period (30 days ±2 days).............................33
4.3.2. Long-term Treatment Period (52 weeks)....................................................34
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4.3.3. End of Treatment (Week 52)......................................................................36
4.3.4. Safety Follow-up ........................................................................................36
4.3.5. Unplanned Visit..........................................................................................37
4.3.6. End of Trial.................................................................................................37
4.4. COVID-19 Emergencies .........................................................................................38
4.5. Post-Study Treatment..............................................................................................38
5. PARTICIPANT POPULATION .........................................................................................38
5.1. Number of Participants............................................................................................38
5.2. Inclusion Criteria.....................................................................................................38
5.3. Exclusion Criteria....................................................................................................39
5.4. Prohibited Concomitant Medications......................................................................42
5.5. Prophylactic and Standard of Care Migraine Medications .....................................43
5.6. Contraception ..........................................................................................................44
6. STUDY CONDUCT AND DESCRIPTION OF STUDY PROCEDURES........................45
6.1. Safety Assessments .................................................................................................45
6.1.1. Vital Signs and Physical Measurements.....................................................45
6.1.2. Physical Examination .................................................................................45
6.1.3. Electrocardiogram (ECG)...........................................................................45
6.1.4. Clinical Laboratory Tests ...........................................................................45
6.1.4.1. Safety Laboratory Testing.........................................................45
6.1.4.2. Pregnancy Test ..........................................................................46
6.2. Efficacy Assessments..............................................................................................46
6.2.1. Daily Migraine Assessment by Severity.....................................................46
6.3. Urine Drug Screening..............................................................................................46
6.4. Serum Virology Testing..........................................................................................47
6.5. Other Assessments ..................................................................................................47
6.5.1. Migraine Quality of Life Questionnaire .....................................................47
6.5.2. Migraine Preference of Medicine ...............................................................47
6.5.3. Satisfaction with Medication Questionnaire...............................................47
6.5.4. Migraine Disability Assessment Questionnaire (MIDAS).........................47
6.5.5. Clinical Global Impression-Change (CGI-c)..............................................47
6.5.6. Demographic Information ..........................................................................47
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6.6. Early Termination of Treatment..............................................................................48
6.7. Early Withdrawal Criteria .......................................................................................48
7. STUDY DRUG MANAGEMENT......................................................................................49
7.1. Overview of Study Drug .........................................................................................49
7.1.1. Basic Information .......................................................................................49
7.1.2. Packaging, Labeling and Storage ...............................................................49
7.2. Dosage and Administration.....................................................................................49
7.2.1. Method of Assigning Participant Numbers ................................................49
7.2.2. Dosage and Administration ........................................................................49
7.2.3. Dose Modification ......................................................................................50
7.3. Blind and Unblinding..............................................................................................50
7.4. Treatment Compliance ............................................................................................50
7.5. Investigational Product Management......................................................................50
8. ADVERSE EVENTS...........................................................................................................52
8.1. Definition of Adverse Events..................................................................................52
8.2. Definition of Serious Adverse Events.....................................................................53
8.3. Definition of Suspected and Unexpected Serious Adverse Reactions....................54
8.4. Method of Collection of Adverse Events and/or Serious Adverse Events .............54
8.5. Time Periods for Collection of Adverse Events and/or Serious Adverse 
Events ........................................................................................................................54
8.6. Follow-up of Adverse Events..................................................................................54
8.7. Recording of Adverse Events..................................................................................55
8.8. Severity of Adverse Events.....................................................................................55
8.9. Indicators for Judging Causality of Adverse Events...............................................56
8.10. Reporting of Serious Adverse Events ...................................................................56
8.11. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, 
and Occupational Exposure.......................................................................................57
8.11.1. Exposure During Pregnancy.....................................................................57
8.11.2. Exposure During Breastfeeding................................................................59
8.11.3. Occupational Exposure.............................................................................60
9. RISK CONTROL AND MANAGEMENT.........................................................................60
10. STATISTICAL CONSIDERATIONS ..............................................................................61
10.1. General Consideration...........................................................................................61
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10.2. Sample Size...........................................................................................................61
10.3. Interim Analysis (IA) ............................................................................................62
10.4. Analysis Populations.............................................................................................62
10.4.1. Full Analysis Set (FAS)............................................................................62
10.4.2. Efficacy Analysis Set (EAS) ....................................................................62
10.4.3. Safety Set (SS)..........................................................................................62
10.5. Statistical Methods ................................................................................................62
10.5.1. Demographic and Baseline Characteristics ..............................................62
10.5.2. Safety Analysis .........................................................................................63
10.5.3. Secondary Endpoints ................................................................................63
10.5.4. Exploratory Endpoints..............................................................................63
11. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................64
11.1. Ethical Conduct and Informed Consent ................................................................64
11.1.1. Review and Approval by Ethics Committee ............................................64
11.1.2. Informed Consent .....................................................................................64
11.2. Data Management and Storage .............................................................................65
11.2.1. Source Data and Source Documents.........................................................65
11.2.2. Data Management.....................................................................................66
11.2.3. Data Protection .........................................................................................67
11.2.4. Preservation of Data .................................................................................68
11.3. Dissemination of Clinical Study Data...................................................................68
11.3.1. Data sharing..............................................................................................69
11.4. Sponsor’s Medically Qualified Individual ............................................................69
11.5. Clinical Monitoring...............................................................................................70
11.6. Quality Control and Assurance .............................................................................70
11.7. Protocol Compliance, Deviations, and Amendments............................................71
11.8. Study Report and Publication................................................................................72
11.8.1. Clinical Trial Report.................................................................................72
11.8.2. Publication and Public Disclosure............................................................72
11.8.3. Publication Policy.....................................................................................72
11.8.4. Public Disclosure Policy...........................................................................72
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11.9. Liability and Insurance..........................................................................................72
11.9.1. Participant Benefits and Privacy Protection .............................................72
11.9.2. Liability and Insurance .............................................................................73
11.10. Archive................................................................................................................73
11.10.1. Investigator File......................................................................................73
11.10.2. Trial Core Document ..............................................................................74
11.11. Duties Assumed by All Parties and Other Relevant Regulations .......................74
11.12. Study Site and Study Staff ..................................................................................77
11.12.1. Main Study Site ......................................................................................77
11.12.2. Data Management and Statistics Unit.....................................................77
11.12.3. Clinical Monitoring Institution...............................................................77
12. APPENDICES ...................................................................................................................78
12.1. Appendix 1 - Potent CYP3A4 Inhibitors and Inducers (Not All).........................78
12.2. Appendix 2 - The definition of "migraine day" ....................................................79
12.3. Appendix 3 - Contraceptive and Barrier Guidance...............................................80
12.3.1. Male Participant Reproductive Inclusion Criteria....................................80
12.3.2. Female Participant Reproductive Inclusion Criteria.................................80
12.3.3. Woman of Childbearing Potential ............................................................80
12.3.4. Contraceptive Methods.............................................................................81
13. REFERENCES ..................................................................................................................83
LIST OF TABLES
Table 1.
Assessment Schedule................................................................................28
LIST OF FIGURES
Figure 1.
Study Schema ...........................................................................................20
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LIST OF ABBREVIATIONS
English 
abbreviation 
English full name 
ACS 
acute coronary syndrome 
ADL
activities of daily living
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
BMI 
body mass index 
BUN 
blood urea nitrogen
BYOD
bring your own device
CGI-c 
clinical global impression – change 
CGRP 
calcitonin gene-related peptide 
CI 
confidence interval 
CK
creatine kinase
COVID-19
Coronavirus 2019
CPK 
creatine phospho kinase 
CRA
Clinical Research Associate/Assistant
CRF 
case report form 
CRO 
contract research organization 
CSR
clinical study report
CT
clinical trial
CTCAE
common terminology criteria for adverse events
CTIS
Clinical Trials Information System
DSM-V 
Diagnostic and Statistical Manual of Mental Disorders Fifth 
edition 
DSU
Drug Safety Unit
EAS
efficacy analysis set
ECG 
electrocardiogram 
eCRF 
electronic case report form 
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English 
abbreviation 
English full name 
EDB
exposure during breastfeeding
EDC 
electronic data capture system 
eDairy 
electronic dairy 
EDP
exposure during pregnancy
eGFR 
estimated glomerular filtration rate 
EOD 
every other day 
EOT
end of treatment
EU
European Union
EudraCT
European Clinical Trials Database
FAS 
full analysis set 
FDA
Food and Drug Administration
FSH 
follicle stimulating hormone 
GCP 
good clinical practice 
HbA1c 
hemoglobin a1c 
HBcAb 
hepatitis b core antibody 
HBeAb 
hepatitis b e antibody 
HBeAg 
hepatitis b e-antigen 
HBsAb 
hepatitis b surface antibody 
HBsAg 
hepatitis b surface antigen 
HBV DNA 
hepatitis b virus deoxyribonucleic acid 
HCV 
hepatitis c virus 
HIV 
human immunodeficiency virus 
ICMJE 
International Committee of Medical Journal Editors 
IA
interim analysis
IB
Investigator's Brochure
IEC
Independent Ethics Committee
IRB
Institutional review board
ISF
Investigator Site File
IV 
intravenous injection 
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English 
abbreviation 
English full name 
LDH 
lactate dehydrogenase 
LFT 
liver function test
LTT 
long-term treatment
MDRD 
modification of diet in renal disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
myocardial infarction 
MIDAS 
migraine disability assessment 
MQI
medically qualified individual
MSQoLQ 
migraine-specific quality of life questionnaire 
NCI
National Cancer Institute
NSAID 
non-steroidal anti-inflammatory drug 
ODT 
orally disintegrating tablet 
OP
observation period 
PCI 
percutaneous coronary intervention 
PoM 
preference of medication 
PPS 
per protocol set 
PRN 
pro re nata 
PSSA
Pfizer SAE Submission Assistant
PT 
preferred term 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
statistical analysis system 
SM 
satisfaction with medication 
SOC 
system organ class 
SOP
standard operating procedure
SRSD 
single reference safety document
SS 
safety set 
SUSAR
suspected unexpected serious adverse event
TEAE 
treatment emergent adverse event 
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English 
abbreviation 
English full name 
TIA 
transient ischemic attack 
UK
United Kingdom
ULN 
upper limit of normal 
WOCBP 
women of childbearing potential 
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1. PROTOCOL SUMMARY
1.1. Synopsis
Protocol Tittle: An Interventional, Phase 3, Single-Arm, Open label Study to Investigate 
Long-Term Safety of Rimegepant Orally Disintegrating Tablets for the Acute Treatment of 
Migraine in Chinese Participants
Brief Title: A study to learn about the long-term safety of rimegepant for the acute treatment 
of migraine in Chinese Participants
Regulatory Agency Identification Number(s):
US IND Number:
N/A
EudraCT/EU CT Number:
N/A
ClinicalTrials.gov ID:  
NCT05371652
Pediatric Investigational Plan Number:
N/A
Protocol Number:
BHV3000-318 (Pfizer C4951018)
Phase:
3
Rationale: A multicenter, open-label study to assess the safety and tolerability of rimegepant 
75 mg ODT (PRN administration, up to 1 tablet per day in mild to severe migraine attacks) 
for the treatment of acute migraine for up to 52 weeks. This study is designed to provide 
long-term safety data in Chinese participants of rimegepant 75 mg dose for the acute 
treatment of migraine. 
Objectives and Endpoints:
Objectives
Endpoints
Primary:
Primary:
To evaluate the long-term safety and tolerability of 
75 mg rimegepant ODT [dosed as needed (PRN)].
Adverse events, common adverse events (incidence ≥
5%), serious adverse events, adverse events leading to 
study drug discontinuation, etc.; ECG, vital 
signs/physical measurements and clinical laboratory test 
abnormalities.
Secondary:
Secondary:
To evaluate the number of migraine days and 
severity of migraine attacks during long-term 
treatment with 75 mg rimegepant ODT (PRN) in 
participants compared to the Observation Period.
Change from Observation Period in the number of 
migraine days by total and moderate or severe pain 
intensity for every 4-week interval and overall period 
during long-term treatment with 75 mg rimegepant 
ODT.
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Overall Design:
This is a multicenter, open-label study to assess the safety and tolerability of long-term use of 
75 mg rimegepant ODT, dosed as PRN, taken up to one tablet per calendar day, in Chinese 
participants with migraine.
The Screening phase includes a Screening Visit and a 30-day Observation Period (OP). For 
participants to be eligible for the study, they must have 6-18 migraine attacks of moderate to 
severe intensity per month in the 3 months prior to the Screening Visit. 
Upon the completion of the Screening Visit, participants will be provided an electronic diary 
(eDiary) to document each day of the 30-day Observation Period if a migraine occurrs, the 
intensity of each migraine attack and if the migraine is treated. Participants will record the 
standard of care migraine treatment received on a personal device APP (BYOD, Bring Your 
Own Device). After the completion of the 30-day OP, participants will return to the clinic for 
the Baseline Visit. At the Baseline Visit, eligibility for the continuing participation in the 
study will be assessed before study medication is dispensed. Participants need have at least 6 
migraine days during the 30-day OP to be eligible and women of childbearing potential 
(WOCBP) must have a negative pregnancy test result prior to dispensing study drug. After 
the investigator reviews the results of the baseline laboratory assessments and determines the 
participant’s eligibility, the site staff will inform the participant whether or not he/she is 
eligible to start dosing in the Long-Term Treatment Phase (LTT). The eligible participants 
will be instructed that they can take a maximum of one tablet of rimegepant per calendar day 
during the 52-week Long-Term Treatment Phase at the onset of a migraine (of mild to severe 
intensity).
Participants are required to record their migraine occurrence and severity via eDiary, and all 
study medication dose and standard of care migraine treatment taken via BYOD. Participants 
will also use BYOD to complete the Preference of Medication (PoM) questionnaire and the 
Satisfaction with Medication (SM) questionnaire at specified study visits. 
At select study visits, participants will complete or will be administered the Migraine-
specified Quality-of-Life Questionnaire v 2.1 (MQoLQ), the Migraine Disability Assessment 
(MIDAS), and Clinical Global Impression-change (CGI-c) scale in the paper scales provided 
by study site.
Additional assessments and visit schedule are outlined in the Schedule of Activities in 
Section 4.3. Activities include study personnel review of the eDiary and BYOD with the 
participant, assessment of study medication compliance, monitoring of tolerability and safety 
(including vital signs, laboratory tests, and electrocardiography). Study visits will be 
approximately every 4 weeks until Week16 and then every 12 weeks for on site visits + every 
4 weeks phone calls in between every two on site visits until Week 52.
Participants will return to the study site at the end of Week 52 (+/- 7 days) for the End of 
Treatment (EOT) Visit. There is a Follow-up Visit 14 days (+/- 2 days) after the Week 
52/EOT Visit.
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Number of Participants: Approximately 330 participants will be screened to enroll 
approximately 240 participants to receive rimegepant treatment.
Study Population: 
Key Inclusion Criteria

Participant has at least 1 year history of migraine (with or without aura) consistent with a 
diagnosis according to the International Classification of Headache Disorders, 3rd 
Edition, beta version. 1, 2

Age of onset of migraines prior to 50 years of age.

Migraine attacks, on average, lasting 4 - 72 hours if untreated.

6-18 migraine attacks of moderate or severe intensity per month within the last 3 months 
prior to the Screening Visit. 

6 or more migraine days requiring treatment during Observation Phase. 

Ability to distinguish migraine attacks from tension/cluster headaches.

Participants on prophylactic migraine medication are permitted to remain on therapy if 
the dose has been stable dose for at least 2 months prior to the Baseline Visit, and the 
dose is not expected to change during the course of the study. Participants who 
previously discontinued prophylactic migraine medication must have done so at least 5 
half-lives of the prophylactic medication prior to the Screening Visit.

Participants with contraindications for use of triptans may be included provided they 
meet all other study entry criteria.
Key Exclusion Criteria

Participants has a history of basilar migraine with brain stem aura or hemiplegic 
migraine.

History of HIV disease.

Current evidence of poorly controlled, unstable, or recently diagnosed cardiovascular or 
cerebrovascular disease such as ischemic heart disease, coronary vasospasm, and cerebral 
ischemia. Myocardial infarction (MI), acute coronary syndrome (ACS), percutaneous 
coronary intervention (PCI), cardiac surgery, stroke, or transient ischemic attack (TIA) 
during 6 months prior to screening. 

Poorly controlled hypertension (high blood pressure) or poorly controlled diabetes (but 
participants with stable hypertension and/or diabetes for at least 3 months prior to 
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screening may be included in the study). Blood pressure greater than 150 mmHg systolic 
or 100 mmHg diastolic after 10 minutes of rest is exclusionary.

Participants with a current diagnosis of major depression or a major depressive episode 
within the last 12 months, other pain syndromes, psychiatric disorders, dementia, or 
significant neurological disorders (other than migraine) that, in the opinion of the 
investigator, might interfere with study assessments.

History of gastric or small intestinal surgery (including gastric bypass, gastric banding, 
gastric sleeve, gastric water ball, etc.) or diseases resulting in malabsorption.

Participant has a history or diagnosis of Gilibert's Syndrome or any other active hepatic 
or biliary disorder.

History or presence of significant and/or unstable medical conditions (e.g., history of 
congenital heart disease or cardiac arrhythmia, known suspected infection, hepatitis B or 
C or neoplasm) that, in the opinion of the investigator, would expose the participants to
undue risk of a significant adverse events (AE) or interfere with the assessment of safety 
or effectiveness during the trial.

History or evidence of alcohol or drug abuse within the past 12 months, or treatment for 
alcohol or drug abuse, or meeting Diagnostic and Statistical Manual of Mental Disorders, 
Fifth Edition (DSM-V) criteria for any significant substance abuse disorder within the 
past 12 months prior to the Screening Visit.

Participants should be excluded if they have a positive drug screen for drugs of abuse and 
are considered medically significant by the investigator, would compromise participant 
safety, or interfere with the interpretation of study results. 

Diagnosis of hematologic or solid malignancy within 5 years prior to screening. 
Participants with a history of localized basal cell or squamous cell skin cancer may be 
included in the study if they are cancer-free prior to the Screening Visit for this study.

Participants with a current diagnosis of schizophrenia, major depression requiring 
treatment with atypical antipsychotics, bipolar disorder or borderline personality disorder. 

Body mass index (BMI) ≥35 kg/m2.

Participants with a history of gallstones or cholecystectomy.
Study Arms and Duration: This is a single-arm study. 
Statistical Methods:
The statistical analysis is mainly descriptive, and no formal hypothesis testing will be 
performed. In general, continuous variables will be descriptively summarized using n, mean, 
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median, standard deviation, minimum and maximum; categorical variables and ordinal 
variables will be summarized using frequency and percentage of each category or grade.
Analysis of adverse events will be mainly based on treatment-emergent adverse events 
(TEAEs). All TEAEs, common TEAEs (incidence ≥5%), serious adverse events (SAEs), and 
TEAEs leading to study drug discontinuation will be summarized and analyzed by system 
organ class (SOC) and preferred term (PT). Vital signs, ECG parameters, and laboratory tests 
and their changes from baseline will be summarized by visit using descriptive statistics. The 
number and percentage of participants with abnormal ECG, vital signs, and laboratory test 
(according to CTCAE grade) will be presented. Liver function test (LFT) elevations will also 
be summarized with number and percentage of participants in pre-specified categories.
For continuous endpoints, two-sided 95% CIs based on normal distribution will be calculated, 
including change from OP in the number of migraine days, and exploratory endpoints defined 
based on MSQoLQ and MIDAS. For categorical and ordinal endpoints, two-sided exact Clopper-
Pearson CIs will be calculated, including the exploratory endpoints defined based on PoM, SM, 
and CGI-c.
1.2. Study Schematic 
Figure 1.
Study Schema
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2. INTRODUCTION AND RATIONALE 
2.1. Therapeutic Area Background 
Migraine is a chronic neurovascular disorder characterized by recurrent attacks and high 
severity. In adults, migraine attacks typically last 4 to 72 hours and are typically 
characterized by unilateral, pulsatile, moderate or severe in severity, exacerbated by daily 
physical activity, accompanied by nausea and/or photophobia and phonophobia. 
Migraine is also a common disfunctional primary headache, which has a high prevalence in 
the population and can pose a significant burden to the socioeconomic and personal life Per 
2017 Global Burden of Disease Survey, it was estimated that 151.6 million (139.9 million to 
163.3 million) of Chinese had migraine, which was the second leading cause of disability for 
participants worldwide in 2016 3,4. In non-elderly adults, the prevalence of migraine in 
Chinese is about 14.3% 5. Despite the increasing availability of drugs for the treatment of 
migraine, inadequate treatment, poor compliance and inadequate access to available drugs 
remain to be the current challenges. 
Rimegepant (PF07899801 [Formerly BHV-3000]) is an oral small molecule calcitonin 
gene-related peptide (CGRP) receptor antagonist under development. CGRP is an 
endogenous 37-amino acid peptide from the pain conduction pathway and is thought to be 
one of the causes of migraine. A variety of clinical evidence suggests that CGRP plays a 
pathological and physiological role in triggering migraine: 1) serum levels of CGRP are 
increased in humans during migraine; 2) anti-migraine drugs can restore CGRP levels to 
normal while relieving pain; and 3) intravenous (IV) CGRP produces long-lasting pain in 
non-migraine participants and migraine participants. CGRP receptor antagonists relieve 
migraine symptoms by 1) blocking CGRP-induced neurogenic vasodilation (to normalize 
dilated intracranial arteries); 2) stopping the cascade of CGRP-induced neurogenic infections 
(resulting in peripheral sensitization); and, when possible, 3) inhibiting central transmission 
of pain signals from the trigeminal nerve to the trigeminal caudate. CGRP receptor 
antagonists reduce migraine symptoms by restoring dilated meningeal arteries to normal, and 
this process does not result in vasoconstriction. 
2.2. Pharmaceutical Development Background 
Details of the clinical and preclinical studies are provided in the most current Investigator 
Brochure (IB). A summary of the relevant data to the study are presented below. 
Rimegepant is approved for acute treatment and prevention of episodic migraine in the US, 
EU and UK and is well tolerated in humans when given as single oral dose of 75 mg to treat 
acute migraine and at a dose of 75 mg EOD for the prevention of episodic migraine. Every 
other day dosing was well tolerated with no signals of hypersensitivity, cardiovascular events 
or hepatotoxicity. 
As of 26 August 2022, more than 8900 unique participants have participated in Phase 1 
studies in healthy participants or Phase 2 and 3 studies in participants with migraine or 
refractory trigeminal neuralgia, chronic rhinosinusitis, or temporomandibular disorders; of 
these, approximately 6036 unique participants have received rimegepant at any dose. 
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Collectively, the current data demonstrates a favorable benefit-risk profile for rimegepant in 
the acute and preventive treatment of migraine. 
2.3. Study Rationale 
Migraine is a chronic neurovascular disorder characterized by recurrent attacks that usually 
last 4 to 72 hours and is accompanied by a variety of symptoms, including typically 
unilateral, pulsatile, moderate, or severe pain intensity, accompanied by nausea or vomiting, 
and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia). The 2016 
Global Burden of Disease Survey ranked migraine as the sixth most prevalent disease and the 
second leading cause of disability worldwide 3, 4. About 14.3% of adults in China suffer from 
migraine 5.From 1990 to 2017, the number of headache cases and participants with 
disabilities in the Chinese population has increased significantly, and most of them are young 
or middle-aged, but headache treatment is not directly and effectively improved during this 
period, resulting in a huge health burden. More attention should be paid to the problem3. 
In part, this burden is attributable to the limitations of the current standard medical therapy, 
i.e., having known cardiovascular disease as well as multiple other cardiovascular risk factors 
are contraindications to these standard drugs. The prescribing information for triptans 
includes warnings and precautions for migraineurs with cardiovascular risk factors and 
states: participants with high risk factors (risk factors include older age, diabetes, 
hypertension, smoking, obesity, or family history of coronary artery disease) should be 
evaluated before receiving the first dose of triptans. Triptans are contraindicated in 
participants with a history of ischemic heart disease, coronary vasospasm, history of stroke, 
peripheral vascular disease, or poorly controlled hypertension. Even in participants with 
negative cardiovascular assessments, the package insert for triptans recommends performing 
the first dose in an environment supervised by a medical professional and examining 
immediately after dosing. In addition, regular cardiovascular assessment should be 
considered in participants with cardiovascular risk factors and long-term use of triptans. 
Since the first entry of triptans into China in the 1990s, there have been no new drugs 
approved for the acute treatment of migraine in China. Thus, there remains significant unmet 
medical needs for novel migraine-specific agents that do not increase cardiovascular risk. 
Rimegepant is a small molecule CGRP receptor antagonist under development for the acute 
phase treatment of migraine, which will address the cardiovascular limitations described 
above. Clinical and nonclinical studies have shown that rimegepant does not cause adverse 
vasoconstriction (these adverse vasoconstrictions are thought to cause serious cardiovascular 
adverse events with triptans) and that its mechanism of action is different from that of other 
drugs causing cardiovascular problems such as non-steroidal anti-inflammatory drugs 
(NSAIDs) and ergotamine derivatives. A Phase 2b dose-finding study showed that 
rimegepant 75 mg was the lowest effective dose and no incremental efficacy benefit was 
observed at the 150 mg, 300 mg, or 600 mg dose levels. The adequate efficacy of the selected 
dose of rimegepant 75 mg compared to placebo was demonstrated in 3 subsequent pivotal 
Phase 3 studies for the treatment of acute migraine, with statistically significant efficacy of 
rimegepant observed for the primary and numerous endpoints in each pivotal study, as 
detailed in the most recent version of the IB. 
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The proposed long-term safety and tolerability study per this protocol will provide further 
safety data on rimegepant for the treatment of acute migraine in Chinese participants and 
bridge the existing complete clinical data on rimegepant 75 mg in the treatment of acute 
migraine. Therefore, this study serves a broad purpose of the rimegepant clinical 
development program: to confirm the safety, tolerability, and effectiveness of rimegepant for 
the treatment of acute migraine with or without aura in adults. 
2.3.1. Study Design Rationale 
A multicenter, open-label study to assess the safety and tolerability of rimegepant 75 mg 
ODT (PRN administration, up to 1 tablet per day in mild to severe migraine attacks) for the 
treatment of acute migraine for up to 52 weeks. This study is designed to provide long-term 
safety data in Chinese participants of rimegepant 75 mg dose for the treatment of migraine. 
Approximately 330 participants will be screened for this study and approximately 240 of 
these participants will be assigned to treatment with 75 mg rimegepant ODT. 
2.3.2. Dose Selection Rationale 
The current Phase 2b dose finding study (CN170003) has demonstrated a comprehensive and 
durable efficacy profile for rimegepant at the 75 mg dose, but not at lower doses (eg, 10 mg 
or 25 mg). 75 mg was selected as the optimal dose to support the Phase 3 clinical trials 
because the higher doses (150 mg, 300 mg, 600 mg) showed a similar efficacy profile to 75 
mg and did not increase benefit. Adequate efficacy of rimegepant 75 mg compared to 
placebo was also demonstrated in 3 subsequent pivotal Phase 3 studies (BHV3000-301, 
BHV3000-302, and BHV3000-303), with statistically significant efficacy compared to 
placebo observed for rimegepant 75 mg across the primary and numerous endpoints in each 
pivotal study. 
At present, the clinical safety results in an open, long-term safety study (BHV3000-201) 
indicate that multiple doses of rimegepant 75 mg in migraine participants are well tolerated 
with a good safety profile within up to 52 weeks. 
2.4. Study Hypothesis 
In the treatment of participants with acute migraine, long-term use of 75 mg rimegepant ODT 
(up to 1 tablet per day, PRN use) is safe and well tolerated. 
2.5. Risk and Benefit Assessment 
Rimegepant is approved in the US, EU, and UK for the treatment of migraine in adults, 
including both acute treatment of migraine and preventive treatment of episodic migraine. 
Rimegepant appears to be generally safe and well tolerated in humans when given as single 
oral doses from 75 mg up to the maximum dose of 1500 mg and multiple oral doses up to the 
maximum daily dose of 600 mg for 14 days. Rimegepant 75 mg represents an advancement 
in migraine therapeutics, providing the first CGRP antagonist to demonstrate benefit for both 
the acute treatment and prophylaxis of migraine. Dual action therapy for migraine with a 
single agent offers patients the potential for significant clinical advantages including: 1) a 
simplified medication regimen to treat migraine across the spectrum from acute episodes to 
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the prevention of future attacks, which are 2 manifestations of the same condition; 2) 
avoiding polypharmacy with concurrent use of multiple medications each with their own side 
effects; 3) reducing the risk of drug-drug interactions; and 4) cost-effectiveness of a single 
medication that provides both acute and preventive therapy.
Broad and sustained efficacy of rimegepant 75 mg was demonstrated in 3 previously 
completed Phase 3 studies (BHV3000-301, BHV3000-302 and BHV3000-303). Statistically 
significant efficacy was demonstrated on the co-primary endpoints of freedom from pain, and 
freedom from most bothersome symptom at 2 hours post-dose. Also, in all 3 studies, 
significant results were achieved on photophobia freedom, phonophobia freedom and pain 
relief at 2 hours post-dose. Similar results were demonstrated in the BHV3000-310 study 
recently completed in China and Korea. In the Phase 2/3 placebo-controlled study 
(BHV3000-305) for the preventive treatment of migraine, rimegepant at a dose of 75 mg 
EOD demonstrated statistically significant superiority to placebo on the primary endpoint of 
change from the observation period in the mean number of migraine days per month on 
treatment in the last month of the double-blind treatment phase.
A multicenter open-label, long-term study (BHV3000-201) was conducted to evaluate the 
safety and tolerability of rimegepant 75 mg tablet taken as needed (up to 1 tablet per day 
upon onset of a migraine of mild, moderate, or severe intensity) for the acute treatment of 
migraine for up to 52 weeks. This multiple-dose, long-term study of rimegepant 75 mg 
administered for up to 52 weeks confirmed the favorable safety profile across a variety of 
safety endpoints, including AE assessments, clinical laboratory testing including LFTs, vital 
signs and ECGs. Safety data from the double-blind treatment and the open-label extension 
phases of the pivotal Phase 2/3, randomized, double-blind, placebo-controlled preventive 
treatment of migraine study (BHV3000-305) support a favorable safety profile of rimegepant 
75 mg administered EOD for the preventive treatment of migraine. Rimegepant 75 mg 
administered EOD + PRN for up to 52 weeks in the open-label phase is well tolerated, with 
no new safety signals observed in the open-label-extension phase. It is not known if it is safe 
to take more than 18 doses of rimegepant in 30 days. Taking into account the measures to 
minimize risk to participants with episodic migraine, the potential risks associated with 
rimegepant are justified by the anticipated benefits that may be afforded to participants with 
daily dosing regimens.
There are no adequate data on the developmental risk associated with the use of rimegepant 
in pregnant women. Women of childbearing potential (WOCBP) must have a negative 
pregnancy test and WOCBP must use an acceptable method of contraception to avoid 
pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. 
Participants undergo regular pregnancy testing throughout the duration of the study. 
Although no safety issues in clinical trials of rimegepant were observed, cardiovascular 
events, cerebrovascular events, hypertensive events, and serious gastrointestinal events 
associated with constipation are reviewed in each aggregate report per FDA request. None of 
these reviews have detected any safety signal associated with these events. Participants are 
excluded if there is uncontrolled, unstable, or recently diagnosed cardiovascular disease or 
hypertension. Participants are monitored through multiple safety endpoints, including AE 
assessments, clinical laboratory testing, vital signs and ECGs.
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Review of all data available, including post-marketing information, nonclinical, clinical, and 
scientific literature data, demonstrates a favorable benefit-risk profile for the use of 
rimegepant in this study. More detailed information about the known and expected benefits 
and risks and reasonably expected AEs of rimegepant may be found in the IB, which is the 
SRSD for this study.
3. STUDY OBJECTIVES AND ENDPOINTS 
3.1. Study Objectives 
3.1.1. Primary Objectives 

To evaluate the long-term safety and tolerability of 75 mg rimegepant ODT (PRN).
3.1.2. Secondary Objectives 

To evaluate the number of migraine days and severity of migraine attacks during long-
term treatment with 75 mg rimegepant ODT (PRN) in participants compared to the 
Observation Period.
3.1.3. Exploratory Objectives 

To evaluate the effect of 75 mg rimegepant ODT treatment compared to baseline on the 
14-Item MSQoLQ version 2.1.  

To evaluate the effect of 75 mg rimegepant ODT treatment on the PoM.

To evaluate the effect of 75 mg rimegepant ODT treatment on the Satisfaction with 
Medication survey.

To evaluate the effect of 75 mg rimegepant ODT treatment compared to baseline on the 
MIDAS.

To evaluate the effect of 75 mg rimegepant ODT treatment on the CGI-c scale.
3.2. Study Endpoints 
3.2.1. Primary Endpoints 

Adverse events, common adverse events (incidence ≥5%), serious adverse events, 
adverse events leading to study drug discontinuation, etc.; ECG, vital signs/physical 
measurements and clinical laboratory test abnormalities. 
3.2.2. Secondary Endpoints 

Change from Observation Period in the number of migraine days by total and moderate 
or severe pain intensity for every 4-week interval and overall period during long-term 
treatment with 75 mg rimegepant ODT.
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3.2.3. Exploratory Endpoints 

Change from baseline in results assessed with the 14-item MSQoLQ version 2.1 
following treatment with 75 mg rimegepant ODT; 

Percentage of participants in each of 3 preference categories of the assessment with 
Migraine PoM for migraine following treatment with 75 mg rimegepant ODT; 

Percentage of participants in each of 7 satisfaction categories of the Satisfaction with 
Medication survey following treatment with 75 mg rimegepant ODT; 

Change from baseline in total score of the MIDAS following treatment with 75 mg 
rimegepant ODT; 

Percentage of participants in each of 7 categories of the CGI-c scale after treatment with 
75 mg rimegepant ODT. 
4. STUDY PLAN 
4.1. Overall Design and Duration 
This will be a multi-center, open-label, long-term safety study of BHV3000 for the treatment 
of acute migraine in Chinese participants to provide the long-term safety data in Chinese 
participants to bridge the existing comprehensive clinical trial data of rimegepant 75 mg dose 
in migraine. Approximately 240 adult participants were planned to be enrolled to receive 
75 mg of rimegepant ODT (PRN use, up to 1 tablet per day).
The screening period will be consisted of a Screening Visit and a 30-day Observation Period. 
Participants must have a history of 6 to 18 moderate to severe migraine attacks per month 
within 3 months prior to the Screening Visit in order to meet the entering criteria of this 
study. 
Upon the completion of the Screening Visit, participants will be provided an electronic 
diary (eDiary) to document each day if a migraine occurrs, the intensity of each migraine 
attack and if the migraine is treated for the 30-day Observation Period. Participants will 
record the standard of care migraine treatment received via BYOD. After completing the 
30-day Observation Period, the participant will return to the clinic with both records for the 
Baseline Visit. At the Baseline Visit, eligibility for continued participation in the study will 
be assessed before study medication will be dispensed. At the Baseline Visit, eligibility for 
continued participation in the study will be assessed, and eligibility will be determined as 
much as possible prior to dispensing study drug, participant need have least 6 migraine days 
during the 30-day Observation Period to be eligible and WOCBP must have a negative 
pregnancy test result prior to dispensing study drug. After the investigator reviews the 
results of the baseline laboratory assessments and determines the participant’s continued 
eligibility, the site staff will inform the participant whether or not he/she is eligible to start 
dosing in the Long-Term Treatment phase. If eligible for the Long-Term Treatment Phase, 
participants will be instructed that they can take study medication at the onset of a migraine 
(of mild to severe intensity). Participants will be instructed that they can take a maximum 
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of one tablet of rimegepant per calendar day during the 52-week Long-Term Treatment 
phase at the onset of a migraine (of mild to severe intensity).
Participants are required to record their migraine occurrence and severity in the eDiary, to 
record all study medication doses via BYOD. Participants are also required to continue to 
record the standard of care migraine treatment taken via BYOD. Participants will also use 
BYOD to complete the PoM questionnaire and the Satisfaction with Medication 
questionnaire at specified study timepoints. 
At select study visits, participants will complete or will be administered the MQoLQ
version 2.1, MIDAS, and CGI-c scale. 
Additional assessments and visit schedule are outlined in the procedural table in Section 4.3
Procedures include study personnel review of the eDiary and BYOD with the participant, 
assessment of study medication compliance, monitoring of tolerability and safety (including 
vital signs, laboratory tests, and electrocardiography). Study visits will be approximately 
every 4 weeks until Week16 and then every 12 weeks for on site visits + every 4 weeks 
phone calls in between every two on site visits until Week 52.
Participants will return to the study site at the end of Week 52 (±7 days) for the End of 
Treatment (EOT) Visit. There is a Follow-up Visit 14 days (±2 days) after the Week 52/EOT 
Visit. 
4.2. Study Schematic 
Refer to Section 1.2.
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4.3. Schedule of Activities
Table 1.
Assessment Schedule
Procedure
Screening 
Visit
Observational 
Period
(30 days, ±2 
days)
Baseline 
Visit
(Day 1)
Phone visit 
to confirm 
eligibility 
based on 
Clinical 
Laboratory 
Findings1
Weeks 4, 
8, 12
(all visits
±3 days)
Weeks 16, 28, 
40, 52 (or Early 
Termination) 
(all visits ±7 
days) 
Phone 
visits 
Weeks 
20, 24, 
32, 36, 
44, 48(all 
visits ±7 
days) 
Follow-up 
Safety 
Visit
(14 days 
after EOT 
visit ±2 
days)
Eligibility Assessments
Informed Consent
X
Inclusion/Exclusion Criteria
X
X
X
Medical History
X
Migraine History 
(signs/symptoms 
/frequency/intensity)
X
Serum virology test
X
Demographic information
X
Prophylactic and standard of 
care migraine medication 
recorded / Concomitant 
Medication via BYOD2
X
X
X
X
X
X3
Safety Assessments
Physical Examination
X
X
X (Weeks 28 and 
52/early 
termination only)
Vital Signs/Physical 
Measurements4
X
X
X
X
X
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Table 1.
Assessment Schedule
Procedure
Screening 
Visit
Observational 
Period
(30 days, ±2 
days)
Baseline 
Visit
(Day 1)
Phone visit 
to confirm 
eligibility 
based on 
Clinical 
Laboratory 
Findings1
Weeks 4, 
8, 12
(all visits
±3 days)
Weeks 16, 28, 
40, 52 (or Early 
Termination) 
(all visits ±7 
days) 
Phone 
visits 
Weeks 
20, 24, 
32, 36, 
44, 48(all 
visits ±7 
days) 
Follow-up 
Safety 
Visit
(14 days 
after EOT 
visit ±2 
days)
Clinical Safety Laboratory 
Testing
X
X
X
X
X
Lipid Panel
X
X (Weeks 28 and 
52/early 
termination only)
ECG
X
X
X (Weeks 28 and 
52/early 
termination only)
X
Urinalysis
X
X
X (Week 52/early 
termination only)
Urine Drug Screen for drugs 
of abuse
X
FSH, if applicable, to 
determine WOCBP status5
X
Pregnancy Test6
X (urine)
X (urine and 
serum)
X(urine)
X (urine)
X (urine)
X (urine)
AE and SAE assessment7
X
X
X
X
X
X
X
Clinical Drug 
Supplies/Study Supplies
Dispense Study Medication8
X
X
X
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Table 1.
Assessment Schedule
Procedure
Screening 
Visit
Observational 
Period
(30 days, ±2 
days)
Baseline 
Visit
(Day 1)
Phone visit 
to confirm 
eligibility 
based on 
Clinical 
Laboratory 
Findings1
Weeks 4, 
8, 12
(all visits
±3 days)
Weeks 16, 28, 
40, 52 (or Early 
Termination) 
(all visits ±7 
days) 
Phone 
visits 
Weeks 
20, 24, 
32, 36, 
44, 48(all 
visits ±7 
days) 
Follow-up 
Safety 
Visit
(14 days 
after EOT 
visit ±2 
days)
Administer study medication9
X
X
X
X
Enter use of study medication 
via BYOD
X
X
X
X
Return unused study 
medication to site for 
compliance check
X
X
Dispense eDiary
X
Install BYOD APP
X
Return eDiary and review e 
Diary and BYOD of 
completion for 
completeness10
X
X
X
Other Assessments
Daily recording of migraine 
attacks and their severity by 
eDiary11
X
X
X
X
X
Migraine Specified Quality 
of Life Questionnaire 
(MQoLQ) v 2.1
X
X (Weeks 
12 only)
X (Weeks 28, 40 
and 52/early 
termination only)
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Table 1.
Assessment Schedule
Procedure
Screening 
Visit
Observational 
Period
(30 days, ±2 
days)
Baseline 
Visit
(Day 1)
Phone visit 
to confirm 
eligibility 
based on 
Clinical 
Laboratory 
Findings1
Weeks 4, 
8, 12
(all visits
±3 days)
Weeks 16, 28, 
40, 52 (or Early 
Termination) 
(all visits ±7 
days) 
Phone 
visits 
Weeks 
20, 24, 
32, 36, 
44, 48(all 
visits ±7 
days) 
Follow-up 
Safety 
Visit
(14 days 
after EOT 
visit ±2 
days)
Preference of Medication
(PoM)
X (Weeks 28 and 
52/early 
termination only)
Satisfaction with Medication 
(SM) Survey
X (Weeks 28 and 
52/early 
termination only)
Clinical Global Impression –
change (CGI-c) 
X (Weeks 28 and 
52/early 
termination only)
Migraine Disability 
Assessment (MIDAS)
X
X (Weeks 
12 only
X (Weeks 28, 40 
and 52/early 
termination only)
1.
Eligibility must be confirmed based on clinical laboratory test results at baseline and migraine occurrence during the observational period before the 
first dose of study drug. Site staff must notify participants by telephone of study eligibility before the participant takes his/her first dose of study drug. 
2.
All concomitant medications, including prophylactic and standard of care migraine medications, as well as medications taken during the observation 
and Long-Term Treatment Periods, should be recorded via BYOD and reviewed by study personnel at each study visit. 
3.
Collect required concomitant medications due to AEs and collect concomitant medications associated with AEs. 
4.
Height will be measured at the Screening Visit only. Participant weight, temperature, respiratory rate, blood pressure, will be collected at all time 
points indicated. Sitting systolic and diastolic arterial blood pressure and pulse rate will be measured. 
5.
If the participant has confirmed the status of WOCBP in the BHV3000-310 trial, the participant is acknowledged to have the same status in this study. 
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Table 1.
Assessment Schedule
Procedure
Screening 
Visit
Observational 
Period
(30 days, ±2 
days)
Baseline 
Visit
(Day 1)
Phone visit 
to confirm 
eligibility 
based on 
Clinical 
Laboratory 
Findings1
Weeks 4, 
8, 12
(all visits
±3 days)
Weeks 16, 28, 
40, 52 (or Early 
Termination) 
(all visits ±7 
days) 
Phone 
visits 
Weeks 
20, 24, 
32, 36, 
44, 48(all 
visits ±7 
days) 
Follow-up 
Safety 
Visit
(14 days 
after EOT 
visit ±2 
days)
6.
Upon completion of the Baseline Visit, WOCBP will be provided with urinary pregnancy test kits so that participants can test at home if necessary. 
When WOCBP participants cannot confirm pregnancy status, a urine pregnancy test must be completed at home before taking study drugs.
7.
All SAEs and AEs must be reported by the participant after signing the informed consent. 
8.
To be determined to be eligible prior to dispensing study drug, participants must have a history of migraine attacks for at least 6 days during the 30-
day Observation Period and WOCBP must have a negative pregnancy test result prior to dispensing study drug. Week 4, 8, 2: dispensing 3 wallets to 
the participant on the monthly visits. Week 16, 28, 40: according to the participant’s need to dispense wallets, maximum is 7 wallets. The study drug 
will not dispense at Week 52 as that is EOT. 
9.
Participants will be instructed that they can take the study medication at the time of their migraine attack (mild, moderate, or severe), up to 1 
tablet per day. The participant must record in the BYOD the study drug taken for each tablet. 
10. If a participant lacks 6 or more eDiary reports per month for 2 months (continuous or non-continuous), the participant's continued participation in the 
study should be terminated due to lack of compliance. 
11. The eDiary will be dispensed at the Screening Visit after the participant has completed all screening procedures. Participants will be trained in the use 
of the eDiary. Participants will use eDiary daily during the observation and Long-Term Treatment Periods to record migraine attacks, migraine 
severity, and whether they receive migraine treatment. 
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4.3.1. Screening Visit, Observation Period (30 days ±2 days) 
The participant or his/her guardian must sign the informed consent form voluntarily in 
writing before participating in the screening. Approximately 330 participants will be 
screened for this study to allow approximately 240 participants to receive treatment of 
rimegepant. 
The main procedures or tests to be completed by the participant at the Screening Visit 
include: 

Signing the informed consent form;

Evaluation of inclusion/exclusion criteria; 

Collection of migraine history (signs/symptoms/frequency/intensity) and other 
medical history; 

Serum virological examination; 

Demographic information; 

Physical examination; 

Vital signs/physical measurements; 

Clinical safety laboratory tests; 

ECG; 

Urine routine; 

Urine drug screen; 

FSH (if applicable); 

Urine pregnancy; 

AE and SAE assessments; 

Dispense eDiary 

Install BYOD APP in the participant mobile phone. 
The eDiary will be dispensed and BYOD APP will be installed after the participant has 
completed all screening procedures at the Screening Visit and the eDiary will be used to 
record migraine attacks and their severity on a daily basis during the Observation Period, as 
well as whether they received migraine treatment. BYOD will be used to record prophylactic 
or standard of care migraine medications/concomitant medications. Participants will be 
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trained in the use of eDiary and BYOD. Height in the physical measurements will only be 
measured at the Screening Visit. If a participant's WOCBP status has been confirmed in the 
BHV3000-310 trial, the participant is recognized to have the same status in this study and a 
repeat FSH test is not required. 
During the Observation Period (30 days ±2 days), the main procedures or examinations to be 
completed by the participant include: 

Recording prophylactic and standard of care migraine medications/concomitant 
medications via BYOD; 

AE and SAE assessments; 

Daily recording of migraine attacks and their severity by eDiary. 
4.3.2. Long-term Treatment Period (52 weeks) 
After completing the 30-day Observation Period, the participants will return to the clinical 
site for the Baseline Visit (Day 1). The main operations or examinations to be completed by 
the participants included: 

Evaluation of inclusion/exclusion criteria; 

Recording prophylactic and standard of care migraine medications/concomitant 
medications via BYOD; 

Physical examination; 

Vital signs/physical measurements; 

Clinical safety laboratory tests; 

Lipid panel

ECG; 

Urine routine; 

Pregnancy test (urine and serum); 

AE and SAE assessments; 

Dispense study drug; 

Return eDiary and review eDiary and BYOD of completion for completeness; 

Daily recording of migraine attacks and their severity by eDiary; 
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
MSQoLQ version 2.1; 

MIDAS. 
After the completion of the relevant items at the Baseline Visit (Day 1), before the 
participants take the study drug for the first time, the clinical site staff should confirm the 
eligibility of the participants for participating in the study based on the examination results at 
the Baseline Visit, and inform the participants by telephone of the eligibility results. The 
participants who meet all the inclusion criteria and do not meet the exclusion criteria can 
participate in the trial. Participants confirmed to be eligible by a telephone visit may start 
taking the study drug, rimegepant 75 mg (up to 1 tablet per day) at the time of a migraine 
attack (mild, moderate, or severe) and record the use of the study drug with BYOD. 
Participants will make site visits at Weeks 4, 8, 12 (±3 days) and Weeks 16, 28, 40, 52 (±7 
days) or Early Termination of the trial and telephone visits at Weeks 20, 24, 32, 36, 44, 48 
for the Long-Term Treatment Period as follows: 

Recording prophylactic and standard of care migraine medications/concomitant 
medications via BYOD; 

Physical examination (Weeks 28 and 52 or early termination); 

Vital signs/physical measurements (at each site visit); 

Clinical safety laboratory tests (at each site visit); 

Lipid panel (at Weeks 28 and 52 or early termination);

Electrocardiogram (at Weeks 28 and 52 or early termination); 

Urine routine (Week 52 or early termination); 

Urine pregnancy (at each site visit and at each telephone visit); 

AE and SAE assessments (at each site visit and at the telephone visit); 

Dispense study drug (at each site visit); 

Take the study drug; 

Record the use of study medication via BYOD; 

Return unused study drug for compliance check (at each site visit); 

Return eDiary and review eDiary and BYOD of completion for completeness (at each 
site visit); 
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
Daily recording of migraine attacks and their severity by eDiary; 

MSQoLQ Version 2.1 (at Weeks 12, 28, 40, 52, or early termination); 

Migraine PoM for migraine (Week 28 and Week 52 or at early termination); 

Satisfaction with Medication survey (Week 28 and Week 52 or Early Termination); 

CGI-c scale (at Weeks 28 and 52 or early termination); 

MIDAS (at Weeks 12, 28, 40, 52 or early termination). 
Upon completion of the Baseline Visit, WOCBP will be provided with urinary pregnancy test 
kits so that participants can test at home if necessary. When WOCBP participants cannot 
confirm pregnancy status, a urine pregnancy test must be completed at home before taking 
study drugs.
During the treatment period, participants have to use the last bottle of study drug before 
opening a new bottle of study drug. Three wallets of study drug will be dispensed to the 
participants at each visit of Week 4, Week 8, and Week 12. Study drug will be dispensed at 
Week 16, Week 28, Week 40 visits as needed, the maximum dispensing limit for each visit is 
7 bottles per participant. Study drug will be dispensed at site visits as needed. Dispensing of 
study drug may also occur at unscheduled visits as needed. 
If a participant lacks 6 or more diary reports per month for 2 months (continuous or non-
continuous), the participant's continued participation in the study should be terminated due to 
lack of compliance. 
4.3.3. End of Treatment (Week 52) 
Participants will have an End-of-Treatment Visit at Week 52 (±7 days) when they have 
completed the trial or at early termination.The site personnel will review the eDiary, assess 
concomitant medications, and complete participant safety tests (including physical 
examination, vital signs/physical measurements, clinical laboratory tests, lipid panel, 
pregnancy tests, and ECGs). Participants will return unused study drug and eDiray to the site. 
4.3.4. Safety Follow-up 
Participants will return to the clinical study site 14 days (±2 days) after the end of treatment. 
The main assessments or examinations to be completed for the participants include: 

Recording prophylactic and standard of care migraine medications/concomitant 
medications via BYOD; 

Vital signs/physical measurements; 

Clinical safety laboratory tests; 
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
ECG; 

Urine pregnancy; 

AE and SAE assessments; 
Concomitant medications required for AEs and associated with AEs will be collected during 
the safety follow-up period. 
4.3.5. Unplanned Visit 
In consideration of the safety of the participants, the investigator may require the participants 
to conduct additional visits or examinations. Results of unscheduled visits or examinations 
will be recorded on the eCRF. 
4.3.6. End of Trial 
The end of the trial includes the completion of the trial and early termination of the trial. If 
either of these situation happens, the trial will be ended, and all participants will 
complete/discontinue from the trial with no further treatment. 
Trial completion is defined as the time when the last participant completes the last visit and 
the sponsor has the right to terminate the trial at any timepoint throughout the trial for 
reasonable reasons. 
Early termination of the trial implies that not all participants have completed all the 
scheduled procedures according to the protocol, and the entire trial or a part of the trial (such 
as a certain site) is terminated. The purpose of premature termination is to protect the rights 
and interests of participants, ensure the quality of the trial, and avoid unnecessary economic 
losses. 
In general, the trial will not be terminated prematurely. However, the entire trial (or a certain 
site) can be terminated prematurely if any of the following situations occurs: 
1
The total sample size is achieved as a result of competitive enrollment, while the site 
may have not completed the planned enrollment as per the contract or have completed 
the trial procedures for all of the participants; 
2
The investigator in the site does not follow the protocol, Good Clinical Practice (GCP), 
etc.; 
3
New informationis received, which indicates unfavorable risk-benefit of the 
investigational drug, including sufficient evidence suggesting lack of efficacy or 
unacceptable safety; 
4
The sponsor considers it to be inappropriate to continue the clinical trial for medical, 
ethical or business reasons; 
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5
Enrolling participants is slow, and it is impossible to complete the study within an 
acceptable time period; 
6
The regulatory authority or ethics committee requests termination of the trial for certain 
reason.
4.4. COVID-19 Emergencies 
If a participant is unable to come to the site for a visit due to the COVID-19 pandemic, it is 
acceptable to conduct remote visits on a case-by-case basis, but the investigator should first 
contact the sponsor medical monitor (or designee) to discuss the most appropriate of action. 
If a laboratory test is required for a remote visit, the local laboratory may be used in place of 
the central laboratory test results and the results are to be obtained and reviewed by the 
investigator. Direct shipment of study drug to participants via an overnight tracked and 
certified courier is also permitted with the approval of the sponsor in advance. 
4.5. Post-Study Treatment 
At the end of the study, the investigator should give the participant appropriate standard 
treatment recommendations for migraine. 
5. PARTICIPANT POPULATION 
5.1. Number of Participants 
Approximately 240 participants will be enrolled in this study. Participants who have 
participated in the BHV3000-310 study may be considered for this long-term safety study if 
they meet all of the criteria for this study, but this cannot be guaranteed. 
5.2. Inclusion Criteria 
1) Signing Informed Consent 
a)
Written informed consent must be obtained from the participant in 
accordance with requirements of the study center’s institutional review board 
(IRB) or ethics committee, prior to the initiation of any protocol-required 
procedures.
2) Target Population 
Participant has at least 1 year history of migraine (with or without aura) consistent 
with a diagnosis according to the International Classification of Headache Disorders, 
3rd Edition, beta version1, 2, including the following:
a)
Age of onset of migraines prior to 50 years of age
b)
Migraine attacks, on average, lasting 4-72 hours if untreated
c)
6-18 migraine attacks of moderate or severe intensity per month within the 
last 3 months prior to the Screening Visit 
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d)
Six or more migraine days requiring treatment during Observation Phase 
e)
Ability to distinguish migraine attacks from tension/cluster headaches
f)
Participants on prophylactic migraine medication are permitted to remain 
on therapy if the dose has been stable dose for at least 2 months prior to 
the Baseline Visit, and the dose is not expected to change during the 
course of the study. Participants who previously discontinued prophylactic 
migraine medication must have done so at least 5 half-lives of the 
prophylactic medication prior to the Screening Visit
g)
Participants with contraindications for use of triptans may be included 
provided they meet all other study entry criteria
3) Age and Reproductive Status 
a)
Male or female participants ≥18 years; 
b)
Participant meets reproductive criteria. Refer to Appendix 3 for 
reproductive criteria for male (Section 12.3.1) and female (Section 12.3.2) 
participants.; 
c)
WOCBP must have a negative pregnancy test at the Baseline Visit prior to 
dispensing study drug; 
4) Other Inclusion Criteria 
a)
No clinically significant abnormality identified on medical or clinical 
laboratory evalution. A participant with a clinical abnormality or 
laboratory parameters outside the reference range may be included only if 
the investigator considers the finding not clinically significant, that it will 
not introduce additional risk factors, nor interfere with the study 
procedures (not including the exclusion criteria listed in Section 5.3). 
5.3. Exclusion Criteria 
1)
Target Disease Exclusion
a)
Participants has a history of basilar migraine with brain stem aura or 
hemiplegic migraine; 
2)
Medical History and Comorbidities 
a)
History of HIV disease 
b)
Current evidence of poorly controlled, unstable, or recently diagnosed 
cardiovascular or cerebrovascular disease such as ischemic heart disease, 
coronary vasospasm, and cerebral ischemia. Myocardial infarction (MI), 
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acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), 
cardiac surgery, stroke, or transient ischemic attack (TIA) during 6 months 
prior to screening; 
c)
Poorly controlled hypertension (high blood pressure) or poorly controlled 
diabetes (but participants with stable hypertension and/or diabetes for at least 
3 months prior to screening may be included in the study). Blood pressure 
greater than 150 mmHg systolic or 100 mmHg diastolic after 10 minutes of 
rest is exclusionary; 
d)
Participants with a current diagnosis of major depression or a major 
depressive episode within the last 12 months, other pain syndromes, 
psychiatric disorders, dementia, or significant neurological disorders (other 
than migraine) that, in the opinion of the investigator, might interfere with 
study assessments; 
e)
History of gastric or small intestinal surgery (including gastric bypass, 
gastric banding, gastric sleeve, gastric water ball, etc.) or diseases resulting 
in malabsorption; 
f)
Participant has a history or diagnosis of Gilibert's Syndrome or any other 
active hepatic or biliary disorder; 
g)
History or presence of significant and/or unstable medical conditions (e.g., 
history of congenital heart disease or cardiac arrhythmia, known suspected 
infection, hepatitis B or C or neoplasm) that, in the opinion of the 
investigator, would expose the participants to undue risk of a significant AE
or interfere with the assessment of safety or effectiveness during the trial; 
h)
History or evidence of alcohol or drug abuse within the past 12 months, or 
treatment for alcohol or drug abuse, or meeting Diagnostic and Statistical 
Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for any 
significant substance abuse disorder within the past 12 months prior to the 
Screening Visit 7; 
i)
Participants should be excluded if they have a positive drug screen for drugs 
of abuse and are considered medically significant by the investigator, would 
compromise participant safety, or interfere with the interpretation of study 
results. In addition: 
i.
Participants with detectable levels of cocaine, amphetamines, and 
phencyclidine in drug abuse screening need to be excluded. Participants 
who are positive for amphetamines on the urine drug screen may have 
their urine samples evaluated for further analysis at the investigator’s 
discretion to rule out a false positive result 
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ii.
Participants with detectable levels of marijuana during substance abuse 
screening may not be excluded if they do not meet DSM-V criteria for 
substance abuse or dependence in the participant's opinion as 
documented by the investigator, and a positive result does not signal a 
clinical condition that would impact the participant safety or 
interpretation of the study results. 
j)
Diagnosis of hematologic or solid malignancy within 5 years prior to 
screening. Participants with a history of localized basal cell or squamous cell 
skin cancer may be included in the study if they are cancer-free prior to the 
Screening Visit for this study; 
k)
Participants with a current diagnosis of schizophrenia, major depression 
requiring treatment with atypical antipsychotics, bipolar disorder or 
borderline personality disorder; 
l)
Body mass index (BMI) ≥35 kg/m2; 
m) Participants with a history of gallstones or cholecystectomy; 
n)
Use of St. John's Wort, products containing St. John's Wort, Coltsfoot root, 
or extracts within 14 days prior to the Baseline Visit; 
o)
Use of narcotic drugs such as opioids (e.g., morphine, codeine, oxycodone, 
and hydrocodone) within 2 days prior to the Baseline Visit. 
3)
Allergy and Adverse Reactions 
a)
History of drug or other allergy that, in the opinion of the investigator, would 
make the participant unsuitable for participation in the study. 
4)
Sex and Reproductive Status 
a)
Women of childbearing potential who are unwilling or unable to use an 
acceptable method of contraception or avoid pregnancy by abstinence for the 
entire study period and for up to 28 days after last dose of study medication; 
b)
Women who are pregnant or breastfeeding; 
c)
Women who have a positive pregnancy test result at screening or prior to 
study drug administration; 
5)
ECG and Clinical Laboratory Test Findings 
a)
Estimated glomerular filtration rate (eGFR) ≤40 mL/min/1.73 m2 according 
to the re-expressed abbreviated (four-variable) Modification of Diet in Renal 
Disease (MDRD) study equation; 
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b)
Corrected QT interval > 470 msec (QTc by method of Frederica) at 
Screening; 
c)
Left Bundle Branch block; 
d)
Right Bundle Branch Block with QRS duration ≥150 msec; 
e)
Intraventricular Conduction Defects with QRS duration ≥ 150 msec; 
f)
Serum bilirubin (Total, Direct or Indirect) 1 × ULN (Only abnormal values 
of between 1-1.5 × ULN may be repeated once for assessment of eligibility 
during the screening period); 
g)
Neutrophil count ≤1000/µL (or equivalent); 
h)
AST or ALT 1 × ULN (Only abnormal values of between 1-1.5 × ULN 
may be repeated once for assessment of eligibility during the Screening 
Period.); 
i)
Glycosylated hemoglobin (HbA1c) >7%. 
6)
Other Exclusion Criteria 
a)
Prisoners or participants who are involuntarilyincarcerated; 
b)
Participants who are compulsorily detained for treatment of either a 
psychiatric or physical (e.g., infectious disease) illness; 
c)
Lack of compliance and/or inability to complete the eDiary during the 
Observation Period. Lack of compliance was defined as more than 4 missed
eDiary times during the Observation Period; 
d)
Participation in a clinical trial with a non-biologic investigational drug (other 
than rimegepant) within 30 days prior to the Screening Visit; 
e)
Participation in a clinical trial with a biological investigational drug within 
90 days prior to the Screening Visit; 
f)
Participation in any other investigational clinical investigators while 
participating in this clinical study. 
5.4. Prohibited Concomitant Medications 
The medications listed below are prohibited starting at the Baseline Visit and during the 
study or as specified: 
1)
St. John’s Wort should not be taken 14 days prior to the Baseline visit and 
throughout the study; 
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2)
Butterbur root or extracts should not be taken 14 days prior to the Baseline visit and 
throughout the study; 
3)
History of use of ergotamine medications on >10 days per month on a regular basis 
for ≥3 months; 
4)
Use of narcotic medication, such as opioids (e.g., morphine, codeine, oxycodone, 
and hydrocodone) was prohibited for at least 2 days prior to the Baseline Visit; 
5)
Use of acetaminophen or acetaminophen containing products for the treatment of 
non-headache symptoms is prohibited after the Baseline Visit. Any use of 
paracetamol or paracetamol-containing products for symptoms other than headache 
during the Observation Period must be discontinued at least 2 days before the 
Baseline Visit; paracetamol may be used during the Long-Term Treatment Period 
as a standard treatment for migraine, as described in Section 5.5. 
6)
Use of triptans is prohibited during the Long-Term Treatment Phase; 
7)
Use of marijuana is prohibited during the study; 
8)
Concomitant use of strong CYP3A4 inhibitors with rimegepant is prohibited during 
the study. If a strong CYP3A4 inhibitor is required (eg, with HIV protease 
inhibitors, hepatitis C protease inhibitors, certain azole antifungals, or 
clarithromycin), dosing with rimegepant should be stopped and should not start 
again until 14 days after the last dose of the strong CYP3A4 inhibitor. Please see 
Appendix 1 Section 12.1. 
9)
Concomitant use of strong CYP3A4 inducers with rimegepant is prohibited during 
the study. If use of a strong CYP3A4 inducer is required (e.g., carbamazepine, 
phenytoin, or rifampin), rimegepant should be discontinued and not be resumed 
until 14 days after initiation of the strong CYP3A4 inhibitor. Please see Appendix 1
Section 12.1. 
10) Concomitant use of atypical antipsychotics such as Abilify® (aripiprazole), 
Zyprexa® (olanzapine), Seroquel® (quetiapine), Geodon® (ziprasidone) or 
Risperdal® (risperidone) or Depakote® /Depakene® (valproic acid/valproate) during 
the Long-Term Treatment Phase;
11) Concomitant use of LAMICTAL ® (lamotrigine) is prohibited during the study. 
5.5. Prophylactic and Standard of Care Migraine Medications
Participants using prophylactic migraine medications are permitted to remain on therapy if 
the dose has been stable for at least 2 months prior to the Baseline Visit and this dose is not 
expected to change during the study. Participants who previously discontinued prophylactic 
migraine medication must have done so at least 5 half-lives of the prophylactic medication 
prior to the Screening Visit.
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Participants may need to take previously prescribed standard of care medications: aspirin, 
ibuprofen, acetaminophen (including Excedrin®Migraine) up to 1000 mg/day for a maximum 
of 2 consecutive days at a time, naproxen (or any other type of non-steroidal anti-
inflammatory [NSAID]), antiemetics (eg, metoclopramide or promethazine), or muscle 
relaxants, which are used during the study (Observation Period and Long-Term Treatment 
Phase) for the standard of care treatment of migraine. 
Use of triptans by participants without a contraindication to their use is allowed during the 
Observation Phase but must be discontinued at the Baseline Visit. As described above, use of 
triptans is prohibited during the Long-Term Treatment Phase. With the exception of triptans 
described in this section, participants are allowed to take standard treatment for migraine 
during the study, if needed, but are required to meet dose restrictions if taking acetaminophen 
(no more than 1000 mg/day at a time for 2 consecutive days). 
If a participant takes a tablet of study drug and experiences a migraine later that day, the 
participant can take standard of care medications for migraine (as described in this section 
above) after taking the study drug that day. Participants are not allowed to take more than 1 
tablet of the study medication per calendar day.
Use of standard of care medications during Observation Period and Long-Term Treatment 
Phase, will be recorded by the participant via BYOD and reported to the site. 
5.6. 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
from the permitted list of contraception methods (see Section 12.3.4) and will confirm that 
the participant has been instructed in its consistent and correct use. 
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. 
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.
WOCBP will complete a pregnancy test at the Screening Visit, at the Baseline Visit, at 
Weeks 4, 8, and at all on-site study visits through the Week 52/end of treatment visit and at 
the Safety follow up Visit. If a WOCBP suspects that she might be pregnant, she should not 
take the study drug and should contact the study doctor immediately.
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6. STUDY CONDUCT AND DESCRIPTION OF STUDY PROCEDURES 
6.1. Safety Assessments 
6.1.1. Vital Signs and Physical Measurements 
Vital signs mainly include blood pressure, pulse rate, respiratory rate and body temperature. 
Vital signs will be measured at the Screening Visit, at the Baseline Visit, at scheduled site 
visits (Weeks 4, 8, 12, 16, 28, 40, 52, or early termination), and at the Safety follow up Visit 
as specified in Table 1. 
Physical measurements mainly include height and weight, and height is only measured at the 
Screening Visit. Weight measurement time and vital signs should be performed according to 
the schedule in Table 1. 
6.1.2. Physical Examination 
Physical examination mainly includes skin, lymph nodes, eyes, head and neck, chest, 
abdomen, spine and limbs. Physical examinations will be performed at the Screening Visit, 
Baseline Visit, scheduled site visits (Week 28, Week 52, or early termination), etc. as 
specified in Table 1. 
The number of physical examinations may be increased if deemed necessary by the principal 
investigator. 
6.1.3. Electrocardiogram (ECG) 
A standard 12-lead ECGs will be performed at the Screening Visit, Baseline Visit, scheduled 
site visits (Week 28, 52, or early termination), and Safety follow up Visit as specified in 
Table 1.
ECG examination indicators mainly include heart rate, PR interval, QRS duration, QT 
interval and QTc interval. 
6.1.4. Clinical Laboratory Tests 
6.1.4.1. Safety Laboratory Testing
Blood and urine samples for clinical laboratory assessments will be collected as outlined in 
Table 1. A central laboratory vendor will be utilized for this study and a laboratory manual 
will be provided to each site. If possible, participants should be fasting for a minimum of 8 
hours before each blood draw. However, if the participant is not fasting at the specified visit, 
the participant should still have blood drawn and the non-fasting status should be 
documented.
1. Clinical Safety Laboratory Tests: 
Hematology: hemoglobin, hematocrit, red blood cell count, white blood cell count 
with differential count, and platelets; 
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Chemistry: Sodium, potassium, chloride, bicarbonate, calcium; glucose, HbA1c, 
BUN (urea), serum creatinine, uric acid, lactate dehydrogenase (LDH), total protein, 
albumin, creatine phosphokinase (CPK) (with fractionation test, if CK result is >1.5 ×
ULN), eGFR using the estimated MDRD formula (calculated at central lab), AST, 
ALT, ALP and bilirubin (Total, Direct, Indirect); 
2. Blood lipid test: cholesterol, low-density lipoprotein, high-density lipoprotein, 
triglyceride; 
3. Urinalysis: pH, specific gravity, ketones, nitrite, urobilinogen, leukocyte esterase, 
protein, glucose and occult blood. Microscopic examination will be performed if 
occult blood, protein or white blood cells are positive; 
4. FSH: for WOCBP at Screening Visit to determine WOCBP status; 
Clinical safety laboratory tests will be performed at the Screening Visit, at the Baseline Visit, 
at scheduled site visits (Weeks 4, 8, 12, 16, 28, 40, 52, or early termination), and at the Safety 
follow up Visit as specified in Table 1; lipid panel tests will be performed at the Baseline 
Visit, at scheduled site visits (Weeks 28, 52, or early termination); urinalysiswill be 
performed at the Screening Visit, at the Baseline Visit, and at scheduled site visits (Week 52 
or early termination); and FSH is used by the study to determine WOCBP status at the 
Screening Visit as appropriate. 
6.1.4.2. Pregnancy Test 
WOCBP will perform pregnancy testing at the Screening Visit, at the Baseline Visit, at 
scheduled site visits (Weeks 4, 8, 12, 16, 28, 40, 52, or early termination), and at the Safety 
follow up Visit as specified in Table 1, along with serum and urine pregnancy tests at the 
Baseline Visit and urine pregnancy tests at other times. Upon completion of the Baseline 
Visit, when WOCBP participants cannot confirm pregnancy status, a urine pregnancy test 
must be completed at home before taking study drugs.
6.2. Efficacy Assessments 
6.2.1. Daily Migraine Assessment by Severity
Participants will be asked to submit electronic records every day after receiving the eDiary 
device including whether migraine occurred, whether migraine was associated with aura, the 
duration of the headache, symptoms, pain features, use of migraine-specific medications 
(study medication, triptan, or ergotamine), as well as severity of the headache. A qualified 
migraine day will be identified using the eDiary data based on the definition in Appendix 2
Section 12.2. The number of migraine days will then be calculated by total and intensity of 
the migraine headache.
6.3. Urine Drug Screening 
A urine drug screen will be performed at the Screening Visit to exclude drug abusers. 
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6.4. Serum Virology Testing
Serum virological examination will be performed at Screening Visit, including HBsAg, HCV 
antibody test, HIV antibody test. HbsAb, HbeAg, HbeAb, HbcAb, and HBV DNA 
quantification will be conducted If HBsAg is positive. 
6.5. Other Assessments 
6.5.1. Migraine Quality of Life Questionnaire 
The MSQoLQ version 2.1 will be used to assess the impact of treatment on participants' 
quality of life. The MSQoLQ has 14 items that have been validated in migraineurs to 
measure the impact of treatment (within past 4 weeks of the questionnaire) on 
migraine-specific domains: work, social function, energy, vitality, feelings, concerns, and 
migraine symptoms 8. 
6.5.2. Migraine Preference of Medicine 
The PoM is a brief scale that captures participants' perception of whether the study 
medication they are taking has a greater benefit compared with previous medications to treat 
their pain. BYOD will be used to evaluate the Preference of Medication Scale.
6.5.3. Satisfaction with Medication Questionnaire 
The Satisfaction with Medication Questionnaire is a brief rating scale that captures
participants' perceptions of whether they are satisfied with the medication for migraine. 
BYOD will be used to evaluate the Satisfaction with Medication Questionnaire.
6.5.4. Migraine Disability Assessment Questionnaire (MIDAS) 
The Migraine Disability Assessment Questionnaire is a retrospective participant self-reported 
rating scale of 5 questions measuring the time lost in headache-related disabilities such as 
headaches due to paid work or school, housework, and nonwork activities. The MIDAS will 
be completed on paper forms at the site 9. 
6.5.5. Clinical Global Impression-Change (CGI-c) 
The CGI-c scale is a brief, observer-rated assment that rates participant total improvement 
relative to the investigator's past experience with other participants with the same diagnosis, 
with or without collateral information9. 
6.5.6. Demographic Information 
Demographic data including age, date of birth, gender, height, weight, ethnicity, etc. will be 
collected at the Screening Visit. These data will be recorded in the original records, and the 
data not involving the participant's personal information or privacy will be recorded in the 
eCRF. 
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6.6. Early Termination of Treatment 
Participants must discontinue study drug (at the discretion of the investigator) for any of the 
following reasons: 

Withdrawal of informed consent (participant withdrawal for any reason); 

The investigator considers the participant should be discontinued from investigational 
product for safety reasons (e.g., the participant develops intolerable adverse events); 

Participant is pregnant; 

The participant experiences a serious protocol devation, and the investigator 
considers that the protocol deviation seriously affects the evaluation of primary 
endpoint of this trial, the investigator considers that the participant should terminate 
the treatment; 

Other conditions that, in the opinion of the investigator, would make the participant 
discontinue trial medication. 
During the trial, all participants who prematurely discontinue treatment should make every 
effort to complete subsequent safety visits. 
6.7. Early Withdrawal Criteria 
Participants who meet the following criteria will be withdrawn from the study: 

Poor participant compliance and inability to comply with the study protocol; 

Participant lost to follow-up; 

The participant withdraws consent and requests withdrawal from the study and 
subsequent follow-up. 
During the trial, the participant may decide to withdraw from the trial treatment and late 
follow-up for any reason at any time. After the participant decides to withdraw, the 
investigator should record the information of withdrawal event of the participant, including at 
least withdrawal date and reason. Lost to follow-up is defined as failure to contact the 
participant after 3 times of telephone calls or other methods, such as mail/registered 
mail/express mail. The investigator should record the specific situation of lost to follow-up, 
including at least the date and way of trying to contact. 
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7. STUDY DRUG MANAGEMENT 
7.1. Overview of Study Drug 
7.1.1. Basic Information 
Drug name: Rimegepant; 
Code: PF-07899801 (Formerly BHV3000); 
Specification: 75 mg; 
Dose form: Orally Disintegrating Tablets (ODT); 
Submitter: Pfizer Inc.
For additional details, please refer to the study drug instruction manual provided by Pfizer 
Inc.to the clinical study site. 
7.1.2. Packaging, Labeling and Storage
In accordance with the requirements of GCP and national regulations, the application of the 
label on the packaging box of investigational drugs will be performed by Pfizer Inc. 
Investigational drugs will be packaged uniformly for all Participants. 
The content of the labels of investigational drugs shall comply with the requirements of GCP 
and national regulations, and shall only be indicated for clinical trials, clinical trial 
information and information of investigational drugs. The specific packaging shall be 
participant to the physical objects. 
Investigational medicinal products should be stored under ambient conditions (temperature 
and light) as specified by the sponsor and in a secure, limited access area. 
The medication will be stored in a locked, environmentally controlled, limited access 
medicine room. 
7.2. Dosage and Administration 
7.2.1. Method of Assigning Participant Numbers 
Participants will be assigned a unique participant number consisting of 5-digit Arabic 
numerals after signing the informed consent form and prior to relevant study examinations: 
the first 2 digits will be the "site number" and the last 3 digits will be the "screening serial 
number". For example, the screening number of the second screener at site 01 is "01002". 
The participant number will be used to identify the participant throughout the study and the 
assigned number will not be reused for other participants in the study. 
7.2.2. Dosage and Administration 
Study drug will be dispensed at the Baseline Visit, and participants will be notified by phone 
after the site staff confirms that the participant is enrolled. Participants confirmed to be 
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eligible can start taking the study drug rimegepant 75 mg (up to 1 tablet per day) at the time 
of their migraine attack (mild, moderate, or severe), and use of the study drug will be 
recorded with BYOD. 
7.2.3. Dose Modification 
There will be no dose adjustment in this study. 
7.3. Blind and Unblinding 
This study is a single-arm trial, blind method and unblinding are not applicable. 
7.4. Treatment Compliance 
Study drug will be dispensed by the responsible study personnel. Drug accountability and 
compliance check results should be documented in the participant's study records. 
Participants should be instructed on the importance of taking the study drug as directed when 
a migraine attack occurs (mild, moderate, or moderate). At site visits, the responsible study 
personnel will review the use of study drug recorded in the BYOD and the returned study 
drug to assess treatment compliance. Dose discrepancies reported by BYOD, review of study 
drug, and information provided by the participant must be documented in the original 
medical record. Data in BYOD for incorrect or missing doses and migraine headaches will be 
corrected by the Data Clarification Record or Study Drug Reconciliation Form. The 
investigator shall inform the participants participating in the study that if it is confirmed that 
the participants are lack of compliance, the participants will be terminated to continue to 
participate in the study. During monthly study visits, if a participant's BYOD records a lack 
of compliance, the study staff should contact the participant and document this contact in the 
original medical record to identify potential participant loss to follow-up as early as possible. 
Investigators should monitor participants for possible abuse of the study drug (participants 
taking the study drug for non-therapeutic purposes, such as for elevated or excited mental 
effects). The investigator should also assess study drug accountability discrepancies (e.g., 
missed study drug, lost study drug, overuse of study drug). In the event of a study drug 
accountability discrepancy, the investigator should obtain additional information and 
explanation from the participant. 
Potential cases of study drug abuse or overdose (including failure to return study drug for 
participants who fail to take the study drug as instructed or discontinue treatment) should be 
recorded in original medical records, and AEs or SAEs should be reported as appropriate. 
Protocol deviations should be documented in the event of dose errors (e.g., taking more than 
1 tablet on a calendar day).
7.5. Investigational Product Management 
The sponsor/its authorized personnel are responsible for providing the investigational product 
to the investigator and the site. The sponsor/its authorized personnel shall not provide the 
investigational drugs to the investigators and clinical trial institutions before the clinical trial 
is approved by the ethics committee and approved or filed by drug regulatory authorities. 
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The sponsor / its authorized personnel should provide the investigator and institution with a 
written description of the investigational product, specifying the use, storage, and records of 
the investigational product. The sponsor/ its authorized personnel will establish procedures 
for investigational product administration and management, including receipt, storage, 
dispensing, use, and return. Investigational products returned from participants and unused 
by study personnel should be returned to the sponsor or destroyed by the study site upon 
authorization by the sponsor. 
The sponsor / its authorized person should ensure that the investigational product is delivered 
to the investigator and institution in a timely manner to ensure that it is used by the 
participants; keep the records of transportation, receipt, distribution, recovery and destruction 
of the investigational product; establish the investigational product recovery management 
system to ensure the recall of defective products, recovery after the trial is completed and 
recovery after expiration. All unused and/or partially used study drug can be sent to the 
predetermined drug destruction facility only after being inspected and reconciled by the 
responsible Study monitor or the sponsor’s designee. If it is site policy to destroy study drug 
on site, it is the Investigator’s responsibility to ensure that arrangements have been made for 
the disposal, procedures for proper disposal have been established according to the applicable 
regulations, guidelines and institutional procedures, and appropriate records of the disposal 
have been documented. Destruction at a study site may only occur after being inspected and 
reconciled by the responsible Study monitor or the sponsor’s designee.
The management of investigational product in the study site is in the charge of the 
investigator's authorized study staff; the investigational product could only be prescribed by 
the principal investigator or the study doctor authorized by the principal investigator, and it 
was necessary to ensure that all investigational products are only used for the participants in 
the clinical trial and their dosage and administration should follow the study protocol; if there 
is a problem in the quality or appearance of the investigational product, the sponsor should be 
contacted immediately; the unused remaining investigational product and empty packages of 
the used investigational product will be returned by the investigator's authorized study staff. 
The investigator should designate a person to be responsible for the receipt, storage, 
dispensing, use, recovery, inventory, and recording of the investigational product, and the 
records should ensure that the contents are completed in a timely and accurate manner; the 
drug receipt form must be signed in duplicate, with the study site and the sponsor holding 
one copy. 
The Clinical Research Associate is responsible for monitoring the receipt, storage, use, 
inventory, and recovery of the remaining investigational product and empty packages of used 
product. After drug accountability at the visit, medication errors, overdose, and drug loss 
should be recorded in the original medical records and eCRF. After checking by the Clinical 
Research Associate, the remaining investigational products and empty packages of used 
drugs will be returned by the sponsor (both parties will sign the drug recovery form). At the 
end of the trial, investigational product shipment records must be consistent with used and 
destroyed/returned quantities. Any discrepancies will be documented and the reason for the 
discrepancy noted. 
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The sponsor / its authorized person should take measures to ensure the stability of the 
investigational product during the trial. The retention period of the samples of investigational 
drug shall be preserved until the end of clinical trial data analysis or the time limit required 
by relevant laws and regulations within the storage period of investigational drug, and the 
longer time limit shall be taken if the two are inconsistent. 
8. ADVERSE EVENTS 
During this study, the investigators (or authorized qualified person) should detect and record 
all adverse events/serious adverse events and pregnancy events observed according to the 
criteria and definitions in this study protocol. Investigators will evaluate adverse events, 
monitor the safety status of participants and provide corresponding protective measures to 
ensure the safety of participants, and report according to relevant requirements.
8.1. Definition of Adverse Events 
According to the definition in GCP, an adverse event is any untoward medical occurrence in 
a clinical trial participant administered an investigational product that may present with 
symptoms/signs, disease, or laboratory abnormalities and which do not necessarily have a 
causal relationship with the investigational product. 
In order to collect more sufficient information, following the participant’s written consent to 
participate in the study, information on clinical adverse events will be collected in this study. 
Any clinical adverse event that occurs after signing the informed consent form and before the 
first use of the investigational product and meets one of the following conditions should be 
recorded as a pretreatment adverse event: injury/damage caused by any clinical laboratory 
test procedure; adverse event caused by drug discontinuation related to the trial protocol; 
adverse event caused by drugs other than the study product (or investigational product) taken 
as part of the treatment regimen. TEAEs are events that start after the first dose of trial drug 
and do not occur or worsen relative to the first dose. 
Examples of an AE include:
1. Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECGs, radiological scans, vital signs measurements), 
including those that worsen from baseline, and felt to be clinically significant in the 
medical and scientific judgement of the investigator.
2. Exacerbation of a chronic or intermittent pre-existing condition including either 
increase in frequency and/or intensity of the condition.
3. New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study.
4. Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
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Examples of NOT meeting definition of an AE include:
1. Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease. However, it was 
considered an AE if the investigator considered the intensity to be more severe than 
the expectation for the participant 's status.
2. The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied. However, it should be considered an AE when its 
severity exceeds the expected severity of the participant 's condition.
3. Medical or surgical procedures (e.g., endoscopy, appendectomy). Note that the 
condition leading to this procedure was an AE.
4. No adverse medical condition, but hospitalization for social reasons and/or 
convenience.
5. Daily fluctuations within the expected range without significant deterioration in the 
underlying disease or condition that were present or detected at the start of the study.
6. Pre-existing conditions or signs and/or symptoms unrelated to the study intervention 
before the first study drug administration; These events will be documented in the 
medical history section of the eCRF.
8.2. Definition of Serious Adverse Events
SAE refers to any untoward medical occurrence that meets any of the following criteria at 
any dose for a participant after receiving the investigational product: death, life-threatening, 
permanent or severe disability or incapacity, hospitalization or prolongation of 
hospitalization required or congenital anomaly or birth defect. 
1. Causing death.
2. Life-threatening: This refers to an adverse event in which the participant was already 
at risk of death at the time of the event, and does not refer to an assumption that the 
adverse event, if more severe, may have caused death.
3. Permanent or significant disability or incapacity: The adverse event result may cause 
serious inconvenience or interference with the participant 's normal life and activities.
4. Requires hospitalization or prolongation of hospitalization: The participant has to be 
hospitalized for treatment due to an adverse event or has been prepared to be 
discharged but has prolonged hospitalization due to an adverse event; it is necessary 
to clarify that the cause of this condition is due to an adverse event rather than 
admission due to elective surgery, non-medical reasons, etc.
5. Congenital anomaly or birth defect: The participant 's offspring have malformation or 
congenital functional defect.
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6. Other important medical events: Medical and scientific judgment must be used to 
determine whether expedited reporting is appropriate for other situations, such as 
important medical events that may not be immediately life-threatening, fatal, or 
hospitalized, but medical measures to prevent one of the above situations are usually 
considered serious. For example, important treatment in the emergency room or 
allergic bronchospasm at home, cachexia or convulsion without hospitalization, drug 
dependence or addiction. 
When it is unclear whether the SAE is considered, the investigator should discuss with the 
sponsor and the Ethics Committee.
8.3. Definition of Suspected and Unexpected Serious Adverse Reactions
Suspected Unexpected Serious Adverse Event (SUSAR) refers to a suspected and
unexpected serious adverse reaction whose nature and severity of the clinical manifestations 
exceed those in the IB of the investigational product, the package insert of the marketed drug 
or the summary of product characteristics.
8.4. Method of Collection of Adverse Events and/or Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
undirected verbal questioning of the participant is the preferred method to inquire about the 
occurrence of AEs. For example:

"How do you feel?"

"Has your health improved or worsened since the last study visit?"

"Have you taken any new medications since your last study visit? Did you stop taking 
or change any medication that you were taking?"
8.5. Time Periods for Collection of Adverse Events and/or Serious Adverse Events
Adverse events, including serious adverse events, will be collected in this study from the 
time the participant signs the informed consent form until the end of the safety follow-up 
period. Investigators were not required to actively collect AEs or SAEs following the 
participant 's safety follow-up period. However, if the investigator learns of any SAE, 
including death, at any time after a participant leaves the study, and considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly collect and report.
8.6. Follow-up of Adverse Events
Following the initial AE/SAE report, the investigator is required to follow each participant 
for further information at subsequent visits/contacts. Each event should be followed until the 
event has resolved (including return to baseline values), the status has changed to long-term 
stability, loss to follow-up, death, or the investigator does not consider continued follow-up 
or other reasonable explanation. The investigator is obligated to perform or arrange for the 
conduct of supplemental measurements and/or evaluations as may be indicated or as 
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requested by sponsor to elucidate as fully as possible the nature and/or causality of the AE or 
SAE.
8.7. Recording of Adverse Events 
When an AE/SAE occurs, investigator shall review all documentation (e.g., hospital progress 
notes, laboratory, and diagnostics reports) relative to the event, and then record all relevant 
information regarding an AE/SAE into the CRF. The investigator will attempt to establish a 
diagnosis of the event based on signs, symptoms, and/or other clinical information. 
Whenever possible, the diagnosis (rather than individual signs/symptoms) was recorded as an 
AE/SAE. If the diagnosis is unknown, AE verbatim terms may be temporarily reported as 
symptoms, signs and abnormal examinations, and each symptom, sign and examination 
should be recorded separately; when the diagnosis is confirmed later, the records should be 
updated.
During the collection and evaluation of AEs and SAEs, truthfully fill in the AE record form, 
including:

AE verbatim term (sign, symptom, diagnosis or syndrome); 

Start date, end date, whether continuous; 

Severity (CTCAE V5.0: Grade 1 ~ 5); 

The investigator's judgment on the causal relationship between the event and the 
investigational product (definitely related, probably related, possibly related, possibly 
unrelated, and definitely unrelated), including the application for suspected 
procedures; 

Action taken for investigational drug; 

Event outcome; 

Whether it is an SAE (if yes, list the specific criteria for SAE); 

Medications and other interventions for AEs treatment. 
8.8. Severity of Adverse Events 
The investigator will summarize the severity of each adverse event by describing the clinical 
symptoms according to the five-grade determination criteria established by NCI CTCAE 
V5.0, which are: 
Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
Grade 2
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL). 
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Grade 3
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL.
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to AE.
8.9. Indicators for Judging Causality of Adverse Events 
Causality assessment is one of the criteria used in determining regulatory reporting 
requirements. The investigator is obligated to assess the relationship between study drugs and 
the occurrence of each AE/SAE using clinical judgement. When the investigator determines 
whether an AE is causally related to the drug, the investigator 's brochure should be 
consulted and the following should be considered:

Whether there is a temporal reasonable relationship between the AE onset and the 
investigational product? AE onset time interval between first and last dose? 

Whether the symptoms and signs present can be caused by the mechanism of action 
of the drug itself or by the action of metabolic components?

Whether the symptoms/signs abated or improved following dose reduction or 
discontinuation and in the absence of other treatment for AEs?

Whether the symptoms/signs reoccures or worsens after re-administration of the study 
drug?

Whether the adverse event can be explained by the participant 's concomitant 
diseases, concomitant medications or other reasons? 

Whether similar situations have been reported in domestic and foreign literatures?
Then, a 5-point method (definitely related, probably related, possibly related, possibly 
unrelated, definitely unrelated) was used to provide a causality assessment of the relationship 
between the reported AE and the use of the investigational product. Definitely related, 
probably related and possibly related will be mapped into ‘related’ and possibly unrelated 
and definitely unrelated will be mapped into ‘unrelated’ via a binary method in the safety 
data base and clinical study report.
For each AE/SAE, the investigator must record, review, and provide a causality assessment 
(although information that the investigator may have known was limited in the event of an 
SAE at some time) and update the causality assessment based on follow-up information.
8.10. Reporting of Serious Adverse Events 
Any SAE must be reported immediately or no later than 24 hours after awareness of the 
event to Pfizer DSU either via the Pfizer SAE Submission Assistant (PSSA) tool or as a 
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written description using the Pfizer CT SAE report form, that must be sent by facsimile (fax 
or eFax) to the Pfizer DSU at 10800714-1806 (north)/ 10800140-1838 (south).Reporting was 
to be completed within 24 hours even if all information on the SAE was not available at that 
time. The investigator should update the SAE report within 24 hours of obtaining additional 
relevant information:
For the reporting of death events, the investigator should provide the sponsor/authorized 
designee and the Ethics Committee with other required information, such as autopsy report 
and final medical report.
The Investigator shall properly maintain written evidence of all reports above to show that 
each event received has been properly reported.
The sponsor will comply with country-specific regulatory requirements regarding safety 
reporting to regulatory authorities, IRBs / IECs, investigational institutions, and investigators, 
and will notify local and other regulatory authorities of safety information about the 
investigational drug as required and in accordance with sponsor policy. The investigator will 
review investigator safety reports received from the sponsor which describing SUSARs or 
other specific safety information, and file them with the IB and notify the Ethics Committee.
The sponsor will promptly investigate SAEs with the investigator and take necessary 
measures to ensure the safety and rights and interests of the participants.
The procedures for follow-up reporting of SAEs are the same as those for initial reporting.
8.11. 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 Exposure During Pregnancy (EDP), Exposure During 
Breastfeeding (EDB), and occupational exposure.
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.11.1. Exposure During Pregnancy
If, following the Baseline Visit it is subsequently discovered that a study participant is 
pregnant or may have been pregnant at the time of the investigational produce exposure, 
including during at least 6 half-lives after the product administration, the investigational 
product will be permanently discontinued in an appropriate manner (i.e., dose tapering if 
necessary for participant safety). Protocol-required procedures for the study discontinued and 
the follow-up must be performed on the participant unless contraindicated by the pregnancy 
(i.e., X-ray studies). Other appropriate pregnancy follow-up procedures should be considered 
if indicated.  The investigator must immediately notify the Pfizer (or designee) Medical 
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Monitor and report the event by either using the PSSA tool and by completing an (EDP) 
Supplemental Form following the SAE reporting procedures as described in Section 8.2. 
Follow-up information regarding the course of the pregnancy, including perinatal and 
neonatal outcome and, where applicable offspring information must be reported on an EDP 
Supplemental Form.
Any pregnancy that occurs in a female partner of a male study ubject should be reported to 
Pfizer DSU. Information on this pregnancy will be collected on an EDP Supplemental Form, 
as appropriate. 
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 or skin contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion 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/participant’s partner, the investigator must report this 
information to Pfizer Safety using the CT SAE Report Form or via PSSA, regardless of 
whether an SAE has occurred. Details of the pregnancy will be collected after the start of 
study intervention and until 66 hours 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 or via PSSA. 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 report is maintained in the investigator 
site file.
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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 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).
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 
followup of birth outcomes will be handled on a case by case basis (eg, followup 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.
8.11.2. 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, 
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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 report is 
maintained in the investigator site file.
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.
8.11.3. 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 or PSSA, 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 report is maintained in the investigator site file.
9. RISK CONTROL AND MANAGEMENT 
According to the information from the previous clinical trial of the investigational drug and 
the clinical study of related products, the most common treatment-related adverse event that 
may occur in participants participating in this trial is nausea. The most frequently reported 
(occurring in ≥2% of participants overall) adverse events, regardless of causality, were: upper 
respiratory tract infection (8.8%), nasopharyngitis (6.8%), sinusitis (5.1%), urinary tract 
infection (3.8%), influenza (3.3%), back pain (3.1%), bronchitis (2.9%), nausea (2.8%), 
dizziness (2.3%), and arthralgia (2.0%).6
In consideration of the above information, the participant's participation in this study may 
cause one or several risks including but not limited to the above adverse events. In this study, 
if the participant experiences adverse drug events, timely intervention should be performed 
according to the protocol requirements and clinical routine treatment measures. 
The trial site must be equipped with necessary medical rescue equipment, emergency drugs 
and emergency measures. If necessary, an emergency medical incident team shall be 
established to handle emergency medical incidents and accidental injuries according to 
relevant standard operating procedures. The investigators must closely observe possible 
adverse events, especially unexpected adverse events, timely analyze and communicate, and 
record adverse events in detail. Contact procedures with the hospital intensive care unit for 
participant transfer and care should be established. The communication and exchange 
between the investigator and the laboratory and the sponsor should be established to ensure 
the timely communication and handling of possible adverse events. 
In this trial, the organ functions (including liver, kidney, hematopoiesis, cardiac function) of 
participants are specified in the inclusion/exclusion criteria, and the participants with cardiac 
diseases, pulmonary diseases and other severe and uncontrolled systemic diseases are 
excluded to avoid the disease aggravation in these participants during the trial. 
Corresponding safety examinations will be performed at the scheduled site visits during the 
treatment period, mainly including vital signs, physical examination, hematology, blood 
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biochemistry (liver function, renal function, electrolyte, etc.), and ECG. Vital signs, physical 
examination, hematology, blood biochemistry, urinalysis, pregnancy test and ECG will be 
performed at the end of treatment period. Through the above examination and the 
observation of the investigator, adverse events should be detected as early as possible, and 
necessary intervention treatment should be given. During the follow-up period, if any adverse 
event or concomitant use or treatment related to adverse event occurs to the participants, it is 
required to report to the investigator in time and come to the hospital for necessary 
intervention if necessary. If the drug is withdrawn due to adverse events related to the 
investigational product, follow-up should be performed until the outcome. 
10. STATISTICAL CONSIDERATIONS 
10.1. General Consideration 
All statistical analyses will be completed using SAS Version 9.4 or higher. In general, 
continuous variables will be statistically described using n, mean, median, standard 
deviation, minimum and maximum; categorical variables and ordinal variables will be 
statistically described using frequency and percentage of each category or grade, and unless 
otherwise specified, the category of missing data will be provided. 
The statistical analysis is mainly descriptive, and no formal hypothesis testing will be 
performed. However, some statistical estimation methods will be used to generate 95% CI. 
10.2. Sample Size 
The sample size for this study is primarily based on historical data, considering the safety 
evaluation and estimation precision for the secondary endpoint. 
For the secondary endpoint of change from Obervation Period in the number of migraine 
days per month from Week 9-12 in participants treated with rimegepant, data from previous 
long-term migraine study BHV3000-2016 showed: 

848 participants with a history of 6-18 days of migraine within 3 months prior to 
baseline; 

Mean (SD) baseline migraine days: 9.92 (3.09); 

Migraine days mean (SD) Weeks 9-12: 8.84 (4.97); 

Change from OP in mean (SD) number of migraine days at Weeks 9-12: -1.08 
(4.74); 
Based on the above historical trial data results and a t distribution assumption, in this single-
arm study, 205 evaluable participants will provide 90% power to observe a negative change 
from baseline in migraine days at Weeks 9-12 for a 1-sided 2.5% significance level, and 
finally 233 participants are required to be included considering 12% dropout rate based on 
BHV3000-201 trial. Considering other possible data loss, approximately 240 participants will 
be finally included. 
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In the case of 240 participants, if the adverse event rate is 5% and 1%, then the probability of 
observing at least one adverse event is >99.9% and 91.0%, respectively, thus providing 
sufficient information for safety and tolerability assessment after LTT with 75 mg 
rimegepant ODT in Chinese participants to bridge the available comprehensive clinical trial 
data of rimegepant 75 mg in the treatment of migraine. 
10.3. Interim Analysis (IA)
This study is an open-label, single-arm study to evaluate the safety and tolerability of 
rimegepant.  The primary objective is safety evaluation and the analysis will be descriptive. 
There will be no alpha spending consideration for the interim analysis. An interim analysis is 
planned when the time is sufficient for at least 175 participants to complete the 12-week visit. 
At IA, with 154 evaluable participants (i.e. 175 treated participants), there will be 80% power to 
observe a negative change from baseline in migraine days at Weeks 9-12 at the 1-sided 2.5% 
significance level. The interim analysis is not for efficacy or futility purpose, but to provide some 
early descriptive readouts for agency communication. Therefore, no decision criteria is needed.
Laboratory test, safety and exposure data will be monitored continuously during the study, 
and be reviewed and summarized by the sponsor/its authorized representative. The final 
clinical study report will be completed when the last participant completes the last visit. 
10.4. Analysis Populations 
10.4.1. Full Analysis Set (FAS) 
All participants who are enrolled and received at least one dose of the investigational 
product. It will be used for the analysis of participant disposition, demographic and baseline 
characteristics, as well as the analyses of exploratory endpoint measures. 
10.4.2. Efficacy Analysis Set (EAS) 
All participants in the FAS with ≥14 eDiary days (not necessarily consecutive) in both the 
Observation Period analysis period and ≥1 month (4-week interval of the LTT analysis 
period). The EAS will be used to assess the secondary endpoint.
10.4.3. Safety Set (SS) 
All participants who received at least one dose of investigational product. The SS will be 
used for safety analyses for this trial. 
10.5. Statistical Methods 
10.5.1. Demographic and Baseline Characteristics 
Demographic data and other baseline characteristics (medical history, prior medications) will 
be tabulated and summarized using descriptive statistics. 
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10.5.2. Safety Analysis 
The primary endpoints of this study are adverse events, common adverse events 
(incidence ≥5%), serious adverse events, adverse events leading to study drug 
discontinuation, etc.; ECG, vital signs/physical measurements and clinical laboratory test 
abnormalities. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). Analysis of adverse events will be mainly based on TEAEs. All TEAEs, 
common TEAEs (incidence ≥5%), SAEs, and TEAEs leading to study drug discontinuation 
will be summarized and analyzed by SOC and PT, and the AEs will be listed by participant. 
Vital signs/physical measurements, ECG parameters, and laboratory tests and their changes 
from baseline will be summarized by visit using descriptive statistics. The number and 
percentage of participants with abnormal ECG, vital signs, and laboratory test (according to 
CTCAE grade) will be presented. LFT elevations will also be summarized with number and 
percentage of participants in pre-specified categories. In addition, these safety data will also 
be listed by participant. 
Additional details can be found in the SAP. 
10.5.3. Secondary Endpoints 
The number of migraine days and severity of migraine attacks will be analyzed for every 4-
week interval and overall period during long-term treatment with rimegepant in participants 
compared to the Observation Period.
Values, changes, and percent changes from OP in the number of migraine days during the 
LTT period will be descriptively summarized by total and moderate or severe pain intensity
for every 4-week interval in LTT and overall LTT period. Two-sided 95% CIs based on 
normal distribution will be calculated for the change from Observation Period and percent 
change from Observation Period in migraine days.
10.5.4. Exploratory Endpoints 
For MSQoLQ and MIDAS rating scales, total and/or domain scores, and changes from 
baseline in the total and/or domain scores will be descriptively summarized by visit with two-
sided 95% CIs based on normal distribution.
For PoM, SM, and CG-c rating scales, number and percentage of participants in each 
category will be summarized by visit with two-sided exact Clopper-Pearson 95% CIs for the 
percentage of participants in each category.  
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11. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
11.1. Ethical Conduct and Informed Consent 
11.1.1. Review and Approval by Ethics Committee 
The Sponsor shall not carry out the clinical trial until obtaining the approval from the Ethics 
Committee. The sponsor/its authorized person should obtain the name and address of the 
Ethics Committee from the investigator and clinical trial institution, a list of Ethics 
Committee members participating in the project review, a review statement in compliance 
with GCP and relevant laws and regulations, as well as documents of approval from the 
Ethics Committee and other relevant materials. 
After ethical review, if it is necessary to modify the protocol, informed consent form, and 
provide the participants and/or other relevant documents, the sponsor should first negotiate 
with the investigator and clinical trial institution, then modify the relevant documents and re-
submit them to the Ethics Committee. 
11.1.2. Informed Consent 
Prior to the initiation of any study procedures, written informed consent will be obtained 
from the participant in accordance with GCP, national laws and regulations. The investigator 
should conduct informed consent in accordance with the basic ethical principles that have 
their origin in the Declaration of Helsinki and in compliance with: 
1. The investigator should use the latest version of ICF approved by the Ethics 
Committee and other information provided to the participants. If necessary, the 
participants shall re-sign the latest version of the ICF during the clinical trial. 
2. When the investigator obtains new information that may affect the participant's 
continued participation in the trial, he/she should promptly inform the participant or 
his/her guardian and make corresponding records. 
3. The investigator shall not force or induce the participants to participate in or continue 
the clinical trial in any improper way. 
4. The investigator or designated study personnel should fully inform the participants or 
their guardians of all the matters related to the clinical trial, including the written 
information and the approval comments from the Ethics Committee. 
5. The oral and written materials provided to participants in the informed consent form 
should be expressed in the language and way that are easy to understand by the 
participants or their guardians and witnesses. 
6. Before signing the informed consent form, the investigator or designated study 
personnel should give the participant or his/her guardian sufficient time and 
opportunity to understand the details of the clinical trial and answer the questions 
related to the clinical trial raised by the participant or his/her guardian in detail. 
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7. The participant or his/her guardian, as well as the investigator who conducted the 
informed consent, should sign and date the informed consent form, respectively, and 
if not signed by the participant, the relationship should be noted. 
8. If the participant or his/her guardian lacks reading ability, an impartial witness should 
be present to witness the entire informed consent process. The investigator should 
explain the contents of the informed consent form and other written materials to the 
participants or their guardians and witnesses in detail. If the participant or his/her 
guardian orally agrees to participate in the trial, he/she should try his/her best to sign 
the informed consent form when capable, and the witness should also sign and date 
the informed consent form to prove that the participant or his/her guardian accurately 
explained the informed consent form and other written information by the 
investigator, understood the relevant contents, and agreed to participate in the clinical 
trial. 
9. The participant or his/her guardian should obtain the original or copy of the signed 
and dated informed consent form and other written materials that should be provided 
to the participant, including the original or copy of the latest version of the informed 
consent form and other revised text that should be provided to the participant. 
10. If the participant is incapable of civil conduct, written informed consent shall be 
obtained from his guardian; if the participant is a person with limited civil conduct 
capacity, written informed consent shall be obtained from himself and his guardian. 
When the guardian provides informed consent on behalf of the participant, he/she 
should inform the participant of the relevant information of the clinical trial to the 
extent that the Participant can understand, and try to have the participant personally 
sign and date the informed consent form. 
11. The specific time of informed consent and the operator should be recorded in the 
medical history record. 
11.2. Data Management and Storage 
11.2.1. Source Data and Source Documents 
Source Data 
Source data refers to all information recorded in original records or certified copies in a 
clinical trial, including clinical findings, observations, and other relevant activity records 
necessary for the reconstruction and evaluation of the clinical trial. 
Source Documents 
Source documents refer to original records, documents and data generated in the clinical trial, 
such as hospital medical records, medical images, laboratory records, memoranda, participant 
diaries or evaluation forms, drug dispensing records, recorded data from automated 
instruments, microfiches, photographic negatives, magnetic media, X-ray films, participant 
files, and documents and records related to the clinical trial maintained by pharmacies, 
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laboratories and medico-technical departments, including certified copies. Source documents 
include source data and may be in the form of paper or electronic carriers. 
CRF 
Electronic case report forms will be used in this trial, and the contents will be filled in by the 
investigator or his/her authorized personnel through the clinical electronic data capture and 
management system (EDC). Before the trial, CRFs are set up in the EDC system and 
assigned to each account of the investigator and/or his/her authorized personnel responsible 
for completing the CRF at the trial site. 
1. For all the participants who have signed the informed consent form, any item in the 
case report form shall be carefully and detailedly recorded according to the 
instructions for filling in the case report form; 
2. All the data in the case report form should be checked with the participant's source 
documents to ensure correctness; 
3. Data significantly deviated from or outside the clinically acceptable range shall be 
verified and, if necessary, judged by the investigator; 
4. See eCRF Completion Guidelines for additional details. 
After the completed eCRFs are reviewed by the CRA, the data manager performs data 
verification and management. After completion of data collection and cleaning, it will be 
signed and confirmed online by the investigator. 
The participant source documents are the original participant records kept at the site. Trial 
data must be entered into the CRF in a timely manner. 
Completed CRFs are the sole property of the sponsor and should not be made available in 
any form to third parties, except for authorized representatives of appropriate regulatory 
authorities or ethics committees, without written permission from the sponsor. 
11.2.2. Data Management 
An electronic data management system will be used for this study. 
1. Construction of Electronic Case Report Form: Data managers constructed eCRF 
according to the study protocol. 
2. Authority assignment: Data administrators shall create accounts and grant different 
authorities according to different identities of entry personnel, investigators and clinical 
research associates. The data entry personnel have the permission of data entry, 
modification and query feedback, the investigator has the permission of modification, 
browsing, query feedback and review, the CRA has the permission of browsing and 
sending query, and the data manager has the permission of browsing, sending query and 
data locking. 
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3. Data entry: Data from the study medical records are entered into the eCRF in a timely 
and accurate manner by the clinical investigator or a data entry clerk (clinical 
coordinator) designated by the investigator. 
4. Query sending and resolution: The monitor and data manager send all queries via eCRF, 
and the entry personnel or investigator answer the questions and modify the wrong data. 
If necessary, the queries can be sent repeatedly, and all records are stored in the eCRF. 
5. Modification and review of data: Data entry personnel or investigators can modify the 
data after verifying the data. For modified data, the reason for modification should be 
filled in the eCRF. The investigator has access to review all final data. 
6. Data locking and export: After all data are reviewed correctly, the data manager locks the 
data. Any modification after data locking can only be implemented after being signed and 
confirmed by the sponsor, investigator, data management personnel and statistician. All 
data are finally exported by data management personnel and submitted to statisticians for 
analysis. 
11.2.3. 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 SOPs on how to respond in the event of unauthorized access, use, or 
disclosure of sponsor information or systems.When participant data are to be deleted, the 
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investigator will ensure that all copies of such data are promptly and irrevocably deleted from 
all systems.
11.2.4. Preservation of Data 
The sponsor, investigator and clinical trial institution should confirm that there are places and 
conditions for preserving the essential documents of clinical trial. The equipment and 
conditions for document preservation shall be equipped with such conditions as preventing 
direct light exposure, water resistance and fire prevention, which is conducive to the long-
term preservation of documents. Standard operating procedures for document management 
should be established. The saved document shall be easy to identify, find, access and home. 
The media used to store the clinical trial data should ensure that the source data or its 
certified copies are kept intact and readable during the retention period and should be tested 
regularly or checked for their ability to resume reading without intentional or unintentional 
alteration or loss. 
For some documents generated in the implementation of clinical trial, if they are not listed in 
the Directory of Essential Documents for Clinical Trial, the sponsor, investigator and clinical 
trial institution may also include them in their respective Essential Documents Files 
according to necessity and relevance. 
For the clinical trial for drug registration application, the essential documents shall be at least 
5 years after the investigational drug is approved for marketing for a clinical trial not used for 
drug registration application, the essential documents shall be kept for at least 5 years after 
the termination of the clinical trial. All materials of this clinical study are proprietary to 
Pfizer Inc. The Investigator shall not provide the information in any form to any third party 
without the written consent of sponsor, unless required by the National Health Commission. 
The sponsor should ensure that the data in the case report forms reported to the sponsor are 
always accessible and can be entered and corrected by the investigator during the trial and 
should not be under the sole control of the sponsor. 
The sponsor should ensure that the investigator can retain the CRF data that has been 
submitted to the sponsor. Copies used as source documents should meet the requirements for 
certified copies. 
At the beginning of the clinical trial, the investigator, clinical trial institution and sponsor 
should establish the archive management for essential documents. At the end of the clinical 
trial, the CRA should review and confirm the essential documents of the investigator, clinical 
trial institution and sponsor, which should be properly kept in the respective clinical trial file. 
11.3. 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.
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In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial 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.
11.3.1. Data sharing
Pfizer provides researchers secure access to participant level data or full CSRs for the 
purposes of “bonafide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
18 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.
11.4. 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 principal investigator ISF.
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To facilitate access to their investigator and the sponsor’s MQI for study related medical 
questions or problems from non-study 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, (c) site 
emergency phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center 
number. 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. The Pfizer Call Center number is to be used when the investigator 
and site staff are unavailable. The Pfizer Call Center number is not for use by the participant
directly; if a participant calls that number directly, they will be directed back to the 
investigator site.
11.5. Clinical Monitoring 
In order to ensure the rights and interests of participants in the trial, ensure the accuracy and 
completeness of trial records and reported data, and ensure that the trial complies with the 
approved protocol, GCP and relevant regulations, the sponsor shall assign qualified monitors 
who have received corresponding training, have sufficient scientific knowledge and clinical 
knowledge required for clinical trial monitoring to monitor the clinical trial. The 
responsibilities of CRA shall comply with the current GCP regulations. After monitoring at 
each visit, the monitor should promptly report to the sponsor in writing and provide the 
sponsor with a monitoring report in compliance with GCP requirements. The sponsor should 
review and follow up the issues in the monitoring report, and form a document for 
preservation. 
11.6. Quality Control and Assurance 
1. The sponsor and/or the contract research organization entrusted by the sponsor shall be 
responsible for developing, implementing and timely updating the standard operating 
procedures for quality assurance and quality control system of the clinical trial to ensure 
that the implementation of the clinical trial and the generation, recording and reporting of 
data comply with the requirements of the trial protocol, GCP and relevant laws and 
regulations. The sponsor may delegate some or all of its clinical trial work and tasks to 
the CRO, but the sponsor is still the ultimate responsible person for the quality and 
reliability of the clinical trial data and should supervise the various work undertaken by 
the CRO. CRO shall implement quality assurance and control. 
2. The whole process of clinical trials and laboratory testing should be conducted in strict 
accordance with the standard operating procedures for quality management. Quality 
control should be performed at each stage of data processing to ensure that all data are 
reliable and that the data processing process is correct. The investigator should receive 
the training on the study protocol, current GCP and relevant standard operating 
procedures before the initiation of the trial, so that the investigator can have a full 
understanding and understanding of the clinical trial protocol and the specific connotation 
of each indicator. 
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3. The sponsor shall sign a contract with the investigator, the clinical trial institution and 
other relevant units participating in the clinical trial to clarify the responsibilities of all 
parties. 
4. The monitoring and audit responsibilities of the sponsor shall be indicated in the contract 
signed by the sponsor and relevant units. The inspection by drug regulatory authorities 
can directly go to the trial site to consult source data, source documents and study report. 
11.7. Protocol Compliance, Deviations, and Amendments 
The investigator and clinical trial institution should conduct the trial in accordance with the 
clinical trial protocol approved by the Ethics Committee. The investigator should not modify 
or deviate from the trial protocol without the consent of the sponsor and the Ethics 
Committee, unless it is to eliminate the emergency hazard to the participants in a timely 
manner, or it only involves the changes in the management of the clinical trial, such as 
changing the monitor, telephone number, etc. The investigator or designated study personnel 
should record and explain the deviation from the study protocol. 
In order to eliminate the urgent harm to the participants, the investigator should promptly 
report to the Ethics Committee and the Sponsor, explain the reasons and report to the drug 
regulatory authorities when necessary, in case of modifying or deviating the trial protocol 
without obtaining the consent from the Ethics Committee. 
The CRA should timely communicate with the investigator about the deviation from the 
study protocol, standard operating procedures and relevant laws and regulations, and take 
appropriate measures to prevent recurrence. 
When the investigator, clinical trial institution and sponsor's personnel are found to be non-
compliant with the trial protocol, standard operating procedures, GCP and relevant laws and 
regulations during the clinical trial, the sponsor should immediately take measures to correct 
them and ensure good compliance with the trial protocol. 
In case of identifying important compliance issues that may affect the safety and rights and 
interests of participants or have a significant impact on the reliability of clinical data, the 
sponsor shall timely conduct root cause analysis and take appropriate corrective and 
preventive measures. If the violation of the study protocol or GCP is serious, the sponsor 
may hold the relevant personnel accountable and report it to the drug regulatory authority. 
When the investigator or clinical trial institution is found to have serious compliance 
problems or the compliance problems still exist after dissuasion, the sponsor shall terminate 
the continued participation of the investigator or clinical trial institution in the clinical trial 
and timely report to the drug regulatory authority in writing. Meanwhile, the sponsor and the 
investigator should take corresponding emergency safety measures to protect the safety and 
rights and interests of the participants. 
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11.8. Study Report and Publication 
11.8.1. Clinical Trial Report 
For the data and information collected during this trial, the clinical trial report will be 
prepared by Pfizer Inc. or its authorized party, and submitted to the signed investigator for 
review and signature. 
11.8.2. Publication and Public Disclosure 
11.8.3. Publication Policy 
At the end of the trial, the investigator may cooperate in the writing of one or more articles 
for co-publication with the consent of Pfizer Inc., and the investigator acts as the first author 
or corresponding author. 
According to the International Committee of Medical Journal Editors (ICMJE) standard (see 
current official version: http://www.ICMJE.org), to determine copyright. The total number of 
authors is based on the guidelines of the relevant journal or conference. In case of any 
disagreement on the contents of the publication, the opinions of the investigator and Pfizer 
Inc. will be fairly and fully reflected in the publication. 
Any external CRO or laboratory participating in the conduct of this trial has no right to 
publish this trial. 
If the investigator wants to independently publish/present any results about the trial, the draft 
of the manuscript/publication must be submitted to Pfizer Inc. in written form before 
submission for comments. Pfizer Inc. will give comments on the draft manuscript received. 
Except for limiting the disclosure of intellectual property rights of Pfizer Inc., this statement 
does not grant Pfizer Inc. any right to edit the publication. If the content of a publication is 
considered patentable by Pfizer Inc., it is not allowed to be published in scientific 
publications until the patent application submitted is published. In this case, the investigator 
may decide to modify or postpone the publication, so that Pfizer Inc. has enough time to seek 
the patent protection of the invention. 
11.8.4. Public Disclosure Policy 
The trial registration policy has been adopted by ICMJE member journals as a condition of 
publication. This policy requires that all clinical trials for publication be first registered on a 
publicly available clinical trial registration network. Therefore, Pfizer Inc. will be responsible 
for the implementation of the study on the appropriate public registration network (i.e., 
designated by NMPA) http://www.chinadrugtrials.org.cn/), registered on this trial. 
11.9. Liability and Insurance 
11.9.1. Participant Benefits and Privacy Protection 
Participants in this trial may not have direct health benefits, but their findings may be of 
benefit to later participants. The participanta are free to participate in all examinations or 
other trial-related operations in this trial. The participants included in this trial will be given 
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traffic compensation each time they come to the hospital, as well as nutritional compensation 
for the participants whose kinetic-related blood samples are collected. Traffic compensation 
and nutrition compensation will be distributed to participants for many times according to the 
progress of the trial. 
All medical records that identify participants by name and test materials will be kept 
confidential as required by law. When reporting adverse events and other trial-related data in 
participants, investigator uses corresponding codes to replace participants' names to protect 
their privacy. The personal information of participants participating in the trial and during the 
trial, including medical history and case records, will be strictly kept confidential. To the 
extent permitted by laws and regulations, representatives of the sponsor, IEC members, and 
representatives of government regulatory authorities may inspect the medical records to 
verify the authenticity, accuracy, and reliability of the study data, without violating the 
principle of confidentiality. 
11.9.2. Liability and Insurance 
The responsibilities of Pfizer Inc., monitor and investigator should be consistent with GCP, 
relevant guidelines and requirements of relevant regulatory authorities in China. The 
investigator shall be responsible for distributing the investigational drugs according to the 
protocol approved by the Ethics Committee or its amendment in accordance with the 
investigator's responsibilities specified in GCP, and the sponsor shall ensure that the 
investigational drugs are timely delivered to the investigator and clinical trial institution, and 
ensure the safe storage and safe handling of the investigational drugs throughout the clinical 
trial. 
Pfizer Inc. will purchase clinical trial liability insurance in accordance with relevant laws in 
China. The costs of treatment for adverse events related to the trial drug or participation in 
the trial will be provided by the sponsor/insurance company. 
11.10. Archive 
11.10.1. Investigator File 
The investigator and clinical trial institution should properly keep the trial documents 
according to the "essential documents for clinical trial" and relevant requirements of drug 
regulatory authorities. The sponsor should specify in the contract with the investigator and 
clinical trial institution the retention time, cost and handling after expiration of essential 
documents. 
The investigator is responsible for completing and maintaining a confidential participant 
identification code list, which refers to the unique code assigned to participants in a clinical 
trial to identify them. When reporting adverse events and other trial-related data in 
participants, investigators use this code instead of participants' names to protect their privacy. 
The trial documents shall not be destroyed without the written authorization of Pfizer Inc. 
and the investigator. If the investigator retires or the site is no longer able to retain the trial 
documents, the trial documents may be transferred to a qualified third party for retention. 
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11.10.2. Trial Core Document 
Pfizer Inc. will archive the core documents of the trial in accordance with GCP and 
applicable regulatory requirements. 
11.11. Duties Assumed by All Parties and Other Relevant Regulations 
1)
Sponsor 
In accordance with GCP regulations, the sponsor shall earnestly perform the following 
responsibilities: 

Initiate and manage the clinical trial and provide the funds required for the trial. 

The sponsor shall take the protection of the rights and interests and safety of 
participants as well as the authenticity and reliability of clinical trial results as the 
basic consideration for clinical trial. 

Select the institutions and investigators for clinical trials, and identify their 
qualifications and conditions to ensure the completion of the trial. 

Before each party to a clinical trial participates in the clinical trial, the sponsor shall 
specify the responsibilities of each party and indicate them in the signed contract. 

The responsibilities, rights and interests of all parties involved in the trial shall be 
specified in the contracts signed by the sponsor with the investigators and clinical 
trial institutions, and the possible conflicts of interest of all parties shall be avoided. 
The test funds in the contract shall be reasonable and comply with the market laws. 
The sponsor, investigator and clinical trial institution should sign the contract for 
confirmation. 

The sponsor should have sufficient safety and efficacy data to support the route, 
dose, and duration of administration when preparing the clinical trial protocol. 
When important new information becomes available, the sponsor will promptly 
update the Investigator's Brochure. 

Before the start of a clinical trial, the sponsor shall submit the relevant clinical trial 
data to the drug regulatory authority and obtain the license for the clinical trial or 
complete the filing. The version number and version date should be specified for 
the documents submitted. 

The sponsor shall obtain from the investigator and clinical trial institution the name 
and address of Ethics Committee, list of Ethics Committee members participating 
in the project review, review statement in compliance with this protocol and 
relevant laws and regulations, documents of approval from Ethics Committee and 
other relevant materials. 
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
The sponsor shall select qualified biostatisticians, clinical pharmacologists and 
clinicians to participate in the trial, including designing trial protocol and case 
report form, preparing statistical analysis plan, analyzing data and writing interim 
and final trial summary report. 

The investigator will be provided with investigational products that are easily 
identified, correctly coded, and specially labeled, and qualified. Investigational 
medicinal products should be appropriately packaged and stored as described in the 
trial protocol. The sponsor shall establish management system and record system 
for investigational drugs. 

The sponsor is responsible for assessing the safety of the investigational product 
during the drug trial. The sponsor shall timely notify the investigators, clinical trial 
institutions and drug regulatory authorities of the problems identified in the clinical 
trial that may affect the safety of participants, may affect the implementation of 
clinical trial and may change the approval comments of Ethics Committee. 

A qualified monitor will be appointed and accepted by the investigator. 

The sponsor and/or entrusted CRO shall establish quality control and quality 
assurance system for the clinical trial and may organize the audit on the clinical 
trial to ensure the quality. 

The sponsor shall specify the access to trial records. The sponsor should specify in 
the trial protocol or contract that the investigators and clinical trial institutions allow 
the monitors, auditors, reviewers of the ethics committee and inspectors from drug 
regulatory authorities to have direct access to source data and documents related to 
the clinical trial. The sponsor should confirm that each participant agrees in writing 
to the direct access of original medical records related to the clinical trial by the 
monitor, auditor, reviewers of the ethics committee and inspectors from drug 
regulatory authorities. 

The sponsor should designate a qualified medical expert to answer and consult the 
medical questions related to the clinical trial in a timely manner. 

The sponsor shall report adverse drug reactions as required and within the time 
limit. 

If the sponsor terminates or suspends the clinical trial in advance, the sponsor shall 
immediately inform the investigator, clinical trial institution and drug regulatory 
authority, and explain the reasons. 

The sponsor should take appropriate measures to ensure that compensation or 
indemnity can be provided to the participants and investigators. The sponsor shall 
provide legal and economic insurance or guarantee related to the clinical trial to the 
investigator and clinical trial institution, which shall be adapted to the nature and 
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degree of risks of the clinical trial, but excluding the damage caused by the 
negligence of the investigator and clinical trial institution. The sponsor shall bear 
the cost of diagnosis and treatment and corresponding compensation for the damage 
or death of participants related to the clinical trial. The sponsor and investigator 
should pay compensation or indemnity to the participants in a timely manner. The 
way and method of compensation provided by the sponsor to the participants shall 
comply with relevant laws and regulations. The sponsor shall provide the 
investigational drugs to the participants for free and pay the medical test fees related 
to the clinical trial. 

The sponsor should ensure the protocol compliance during the implementation of 
the clinical trial. If the investigator or clinical trial institution is found to have 
serious compliance problems or still does not change after dissuasion, the sponsor 
shall terminate the continued participation of the investigator or clinical trial 
institution in the clinical trial and timely report to the drug regulatory authority in 
writing. Meanwhile, the sponsor and the investigator should take corresponding 
emergency safety measures to protect the safety and rights and interests of the 
participants. 

Upon completion or early termination of a clinical trial, the sponsor shall submit a 
clinical trial report to the drug regulatory authority in accordance with applicable 
laws and regulations. The clinical trial close-out report shall comprehensively, 
completely and accurately reflect the clinical trial results. The safety and 
effectiveness data in the close-out report shall be consistent with the source data of 
the clinical trial. 
2)
Study Site and Investigator 
In accordance with GCP regulations, the investigator and clinical trial institution shall 
earnestly perform the following responsibilities: 

The investigator and clinical trial institution should have the qualifications 
required by GCP. 

The investigator and clinical trial institution should have the necessary conditions 
to complete the clinical trial. 

The investigator should provide appropriate medical treatment for the participant. 

The investigator should communicate with the Ethics Committee. 

The investigator should follow the trial protocol. 

The investigator and clinical trial institution have administrative responsibility for 
the investigational product provided by the sponsor. 
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
The investigator should follow the randomization procedure of the clinical trial. 

The investigator should conduct informed consent in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, in accordance with 
GCP, and provide the informed consent form and other necessary materials to the 
participants. 

The records and reports of the trial should meet the requirements of GCP. 

The investigator's safety report should meet the GCP requirements. 

When the Ethics Committee decides to terminate the clinical trial in advance, the 
investigator should immediately report to the study site and the sponsor with 
reasons stated. 

In case of premature termination or suspension of the clinical trial, the 
investigator should timely inform the participants, give the participants 
appropriate treatment and follow-up visit, and fulfill other requirements stipulated 
in GCP. 

The investigator should provide a trial progress report. 
3)
Data Management/Statistical Unit 
According to the provisions of GCP, the data management and statistical personnel of this 
trial shall earnestly fulfill their responsibilities. Upon completion of the trial, the data 
management and statistical personnel is responsible for data management, making 
statistics for the data according to the formulated statistical plan and issuing the statistical 
analysis report. 
11.12. Study Site and Study Staff
11.12.1. Main Study Site 
Name of study institution: Chinese PLA Gerneral Hospitcal
11.12.2. Data Management and Statistics Unit 
Organization name: Hangzhou Tigermed Consulting Co., Ltd
11.12.3. Clinical Monitoring Institution 
Organization name: Hangzhou Tigermed Consulting Co., Ltd
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12. APPENDICES 
12.1. Appendix 1 - Potent CYP3A4 Inhibitors and Inducers (Not All) 
The following medications and concomitant medications are potent inhibitors of some 
CYP3A4. This list does not include all such drugs. Concomitant use of strong CYP3A 
inhibitors is prohibited as described in the study protocol. 
Strong CYP3A Inhibitors 
Boceprevir, cobicistat, konivaptan, danoprevir and ritonavir, etegravir and ritonavir, indinavir and ritonavir, 
itraconazole, ketoconazole, lopinavir and ritonavir, paraprevir and ritonavir (obitavir and/or dalatavir), 
posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, teiranavir and ritonavir, troleandomycin, 
voriconazole, clarithromycin, nefazodone, nelfinavir 
The following medications and supplements are strong inducers of some CYP3A4. This list 
does not include all such drugs. Concomitant use of strong CYP3A inducers is prohibited as 
described in the study protocol. 
Strong CYP3A Inducers 
Carbamazepine, phenytoin, rifampin, St. John's Wort 
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12.2. Appendix 2 - The definition of "migraine day"
The term "migraine day" referred in the term "migraine attack days" in the secondary 
objective of Section 3.1.2 of protocol are interpreted as follows:
Migraine Day: Any calendar day in which the participant experiences a qualified migraine 
headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine 
headache is defined as a migraine with or without aura, lasting for ≥30 minutes, and meeting 
at least one of the following criteria (a and/or b)
a) ≥2 of the following pain features:

Unilateral location,

Pulsating quality (throbbing),

Moderate or severe pain intensity,

Aggravation by or causing avoidance of routine physical activity (e.g. walking or 
climbing stairs)
b) ≥1 of the following associated symptoms:

Nausea and/or vomiting

Photophobia and phonophobia
If the participant took a migraine-specific medication (i.e., study medication [open-label, 
extension phase only], triptan or ergotamine) during aura or to treat headache on a calendar 
day, then it will be counted as a migraine day regardless of the duration and pain 
features/associated symptoms.
The use of study medication on non-scheduled dosing days is only permitted during the 
openlabel, extension phase.
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12.3. Appendix 3 - Contraceptive and Barrier Guidance
12.3.1. Male Participant Reproductive Inclusion Criteria
No contraception methods are required for male participants in this study, as the calculated 
safety margin is ≥100 fold between the estimated maternal exposure due to seminal transfer 
and the NOAEL for serious manifestations of developmental toxicity in nonclinical studies.
12.3.2. Female Participant Reproductive Inclusion Criteria
The criteria below are part of Inclusion Criterion 2.b (Age and Sex; Section 5.2) and specify 
the reproductive requirements for including female participants. Refer to Section 12.3.4 for a 
complete list of contraceptive methods permitted in the study. 
A female participant is eligible to participate if she is not pregnant or breastfeeding and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 12.3.3). 
OR

Is a WOCBP and agrees to use an acceptable contraceptive method during the 
intervention period (for a minimum of 28 days after the last dose of study 
intervention).  The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
12.3.3. 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 or oligomenorrhea) and a menstrual cycle cannot be 
confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenarchal.
2. Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy
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
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.
3. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition:

A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age 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.
12.3.4. Contraceptive 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. Implantable progestogen‑only hormone contraception associated with inhibition of 
ovulation.
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 
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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 
6. Combined (estrogen‑ and progestogen‑containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal.
7. Progestogen‑only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
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.
Other Effective Methods
9. Progestogen‑only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom, with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double‑barrier methods).
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13. REFERENCES 
1
IHS. International Classificaton of Headache Disorders, 3rd edition beta version. 2013.
2
于生元等.国际头痛分类第3 版（beta 版）中文版翻译.https://ichd-3.org/wp-
content/uploads/2018/10/ICHD-3-Chinese.pdf.
3
Yao C, Wang Y, Wang L, etal. Burden of headache disorders in China,1990–2017: findings 
from the Global Burden of Disease Study 2017 [J]. The Journal of Headache and Pain, 
2019, 20.
4
GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, 
and national incidence, prevalence, and years lived with disability for 328 diseases and 
injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of 
Disease Study 2016 [J]. Lancet, 2017, 390: 1211–1259.
5
Takeshima T, Wan Q, Zhang Y, etal. Prevalence, burden, and clinical management of 
migraine in China, Japan, and South Korea: a comprehensive review of the literature[J]. 
The Journal of Headache and Pain, 2019, 20.
6
BHV3000-110-CSR. A Phase 1, Study to Evaluate the Bioequivalence Between Two 
Tablet Formulations of Rimegepant and to Evaluate the Relative Bioavailability of a 
Sublingual Orally Disintegrating Tablet of Rimegepant in Healthy Adult Subjects Under 
Fasting Conditions. Biohaven Pharmaceuticals, Inc, 2018.
7
APA. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5 5th 
Edition. 5th ed, ed. A.P. Association. 2013: American Psychiatric Publishing.
8
Patrick DL, Hurst BC, Hughes J. Further development and testing of the migraine-specific 
quality of life (MSQOL) measure[J]. Headache, 2000, 40(7):550-560.
9
Lipton RB, Stewart WF, Sawyer J, etal. Clinical utility of an instrument assessing migraine 
disability: the Migraine Disability Assessment (MIDAS) questionnaire[J]. Headache,
2001, 41(9): 854-861.
10 Guy W. ECDEU Assessment Manual for psychopharmacology. Rockville, Md.: U.S. 
Department of Health, Education, and Welfare Public Health Service Alcohol, Drug 
Abuse, and Mental Health Administration, National Institute of Mental Health, 
Psychopharmacology Research Branch, Division of Extramural Research Programs.1976.
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SAP_001.pdf: 
Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1  of 3 6  
 
 
 
 
 
 
A M ultice nter, O pe n l a bel, L o n g -ter m S afet y St u d y of B H V 3 0 0 0 f or t he 
Ac ute Tre at me nt of Mi gr ai ne i n C hi nese P artici p a nt s 
 
B H V 3 0 0 0 -3 1 8/ C 4 5 9 1 0 1 8  
 
Fi n al  A n al ysis Pl a n  
 
 
 
 
 
Versi o n: 1. 0  
 
D ate: A pril  0 7 , 2 0 2 4  
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2  of 3 6  
 
 
 
 
 
 
 
A M ultice nter, O pe n l a bel, L o n g -ter m S afet y St u d y of B H V 3 0 0 0 f or t he 
Ac ute Tre at me nt of Mi gr ai ne i n C hi nese P artici p a nt s 
 
B H V 3 0 0 0 -3 1 8/ C 4 5 9 1 0 1 8  
 
 
Fi n al  A n al ysis Pl a n  
 
Versi o n: 1. 0  
 
 
 
Pre pare d b y:  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Date: _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Ha n gz h o u Ti ger me d C o ns ulti n g C o., Lt d.  
 
 
 
 
Re vie we d b y:  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Date: _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Ha n gz h o u Ti ger me d C o ns ulti n g C o., Lt d.  
 
 
 
 
 
 
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P P D
P P D


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3  of 3 6  
 
 
 
A p pr o ve d b y:  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Date: _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Pfizer ( C hi na) 
 
C o., Lt d.  
 
 
 
 
A p pr o ve d b y:  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Date: _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Pfizer ( C hi na) 
 
 C o., Lt d. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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P P D
P P D
P P D
P P D


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 4  of 3 6  
 
 
 
 
R E VI SI O N  HI S T O R Y  
V E R SI O N  
V E R SI O N D A T E  
A U T H O R  
D E S C RI P TI O N  
1. 0  
0 7 -A pr -2 0 2 4  
 
O RI GI N A L V E R SI O N  
 
 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)
P P D


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 5  of 3 6  
 
 
T a ble of C o nte nts  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S  ............................................7  
1  
I N T R O D U C TI O N .............................................................................................................9  
2  
S T U D Y O BJ E C TI V E S  ......................................................................................................9  
2. 1  
Pri mar y O bjecti ve  ....................................................................................................9  
2. 2  
Sec o n dar y O bj ecti ve  ................................................................................................9  
2. 3  
E x pl orat or y O bjecti ves  ............................................................................................9  
3  
S T U D Y D E SI G N ...............................................................................................................9  
3. 1  
O verall Desi g n  .........................................................................................................9  
3. 2  
Ra n d o mizati o n  .......................................................................................................1 1  
3. 3  
Bli n di n g ..................................................................................................................1 1  
3. 4  
Sa m ple Size Calc ulati o n  ........................................................................................1 1  
4  
S T U D Y E N D P OI N T S  .....................................................................................................1 2  
4. 1  
Pri mar y E n d p oi nts  .................................................................................................1 2  
4. 2  
Sec o n dar y E n d p oi nt  ...............................................................................................1 2  
4. 3  
E x pl orat or y E n d p oi nts  ...........................................................................................1 2  
5  
S T U D Y  H Y P O T H E SI S  ...................................................................................................1 2  
6  
A N A L Y SI S S E T S  ...........................................................................................................1 2  
7  
S T A TI S TI C 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  .........................................1 3  
7. 1  
Ge neral Met h o ds  ....................................................................................................1 3  
7. 2  
Data Pr ocessi n g R ules ............................................................................................1 3  
7. 2. 1  
Ha n dli n g of Missi n g Data  ............................................................................1 4  
7. 2. 2  
Ot her Data Pr o cessi n g R ules  .......................................................................1 4  
7. 2. 3  
Deri ve d D ates ...............................................................................................1 5  
7. 2. 4  
A nal ysis Peri o ds ...........................................................................................1 6  
7. 2. 5  
A nal ysis Visit Wi n d o ws  ..............................................................................1 6  
7. 3  
St u d y Partici pa nts  ..................................................................................................1 7  
7. 3. 1  
Partici pa nt Dis p ositi o n  .................................................................................1 8  
7. 3. 2  
Pr ot oc ol De viati o ns  ......................................................................................1 8  
7. 3. 3  
De m o gra p hics/ Baseli ne C haracteristics  .......................................................1 8  
7. 3. 4  
Mi grai ne Hist or y  ..........................................................................................1 9  
7. 3. 5  
Me dical Hist or y  ...........................................................................................1 9  
7. 3. 6  
Pri or a n d C o nc o mita nt Me dicati o ns  ............................................................1 9  
7. 3. 7  
Pri or a n d C o nc o mita nt N o n -dr u g T hera pies  ................................................2 0  
7. 3. 8  
Dr u g Acc o u nta bilit y a n d e Diar y C o m plia nce  ..............................................2 0  
7. 4  
Efficac y A nal yses  ..................................................................................................2 1  
7. 4. 1  
Efficac y A nal ysis of t he Sec o n dar y E n d p oi nt  .............................................2 1  
7. 4. 2  
Efficac y A nal ysis of t he E x pl orat or y E n d p oi nts  .........................................2 2  
7. 5  
Safet y A nal yses  ......................................................................................................2 4  
7. 5. 1  
Dr u g E x p os ure  .............................................................................................2 4  
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Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 6  of 3 6  
 
 
7. 5. 2  
A d verse E v e nts  ............................................................................................2 5  
7. 5. 3  
Cli nical La b orat or y Tests  .............................................................................2 7  
7. 5. 4  
Vital Si g ns a n d P h ysical Meas ure me nts  ......................................................2 9  
7. 5. 5  
1 2 -lea d E C G.................................................................................................3 0  
7. 6  
C O VI D -1 9 -relate d Visit I m pact ............................................................................3 0  
8  
A P P E N DI X  ......................................................................................................................3 0  
8. 1  
T he Deri v ati o n of Mi grai ne Da y ............................................................................3 0  
8. 2  
T he Ma p pi n g R ule f or P D Cate g ories  ...................................................................3 3  
9  
R E F E R E N C E S  ................................................................................................................3 5  
 
 
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Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 7  of 3 6  
 
 
List of A b bre vi ati o ns a n d Defi niti o ns of Ter ms  
A b bre vi ati o n  
Defi niti o n  
A E  
A d verse E v e nt  
A L P  
Al kali ne P h os p hatase  
A L T  
Ala ni ne Tra ns a mi nase  
A S T  
As parate Tra nsa mi nas e  
A T C  
A nat o mical T hera pe utic C he mical Classificati o n of Dr u gs  
B MI  
B o d y Mass I n d e x  
B Y O D  
Bri n g Y o ur O w n De vi ce  
C GI -c  
Cli nical Gl o bal I m pr essi o n -c ha n ge  
CI  
C o nfi de nce I nter val  
C P K  
Creati ne P h os p h o Ki nase  
C R F  
Case Re p ort F or m  
C T C A E  
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts  
DI LI  
Dr u g -I n d u ce d Li ver I nj ur y 
E A S  
Efficac y A nal ysis S et 
E C G  
Electr ocar di o gra m  
e Diar y 
Electr o nic Diar y  
e DI S H  
Dr u g -I n d u ce d Seri o us He pat ot o xicit y 
e G F R  
Esti mate d Gl o mer ular Filtrati o n Rate  
F A S  
F ull A nal ysis Set  
F S H  
F ollicle Sti m ulati n g H or m o ne  
F U S S  
F oll o w -u p Safet y A n al ysis Set  
H b A 1c  
He m o gl o bi n A 1c  
L D H  
Lactate D e h y dr o g e nase  
L T T  
  L o n g -Ter m Treat me nt  
M D R D  
M o dificati o n of Diet i n Re nal Diseas e  
Me d D R A  
Me dical Dicti o nar y f or R e g ulat or y Acti vities  
MI D A S  
Mi grai ne Disa bilit y Assess me nt  
M S Q o L Q  
Mi grai ne -S pecifi c Q ualit y of Life Q uesti o n nair e  
N  
N u m ber  
N CI  
Nati o nal Ca ncer I nstit ute  
O D T  
Orall y Disi nte grati n g Ta blet  
O P  
O bser vati o n Peri o d  
P o M  
Prefere nce of Me dicati o n  
P R N  
Pr o re nata  
P T  
Preferre d Ter m  
S A E  
Seri o us A d verse E v e nt  
S A P  
Statistical A nal ysis Pla n  
S S  
Safet y A nal ysis Set  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 8  of 3 6  
 
 
S B P  
S yst olic Bl o o d Press ure  
S D  
Sta n dar d De viati o n  
S M  
Satisfacti o n wit h Me dicati o n  
S O C  
S yste m Or ga n Class  
T B L  
T otal Bilir u bi n  
T E A E  
Treat me nt E mer ge nt A d v erse E ve nt  
U L N  
U p per Li mit of N or mal  
W O C B P  
W o m en of C hil d beari n g P ote ntial  
W H O -D D  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
 
 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 9  of 3 6  
 
 
1  
I ntr o d ucti o n 
T his Statistical  A nal ysis Pla n is base d o n t he fi nal st u d y pr ot oc ol B H V 3 0 0 0 -3 1 8 ( Pr ot oc ol 
Versi o n 5 . 0, date d 1 8 A u g 2 0 2 3 ) a n d fi n al case re p ort f or m (C R F,  Versi o n 3 . 0, date d 
2 1 Mar 2 0 2 3 ). F or t he details f or i nteri m a nal ysis, refer t o I nteri m A nal ysis P la n (Versi o n 1 . 0, 
date d 1 1 A pr 2 0 2 3 ). 
2  
S T U D Y O B J E C TI V E S  
2. 1  Pri m ar y O bjecti ve  
T o e val uate t he l o n g -ter m safet y a n d t olera bilit y of 7 5 m g Ri me ge pa nt O D T [ d ose d as nee d e d 
( P R N)]. 
2. 2  Sec o n d ar y O bjecti ve  
T o e val uat e t he n u m ber of mi grai ne da ys a n d s e verit y of mi grai ne attac ks d uri n g l o n g -ter m 
treat me nt ( L T T) wit h 7 5 m g Ri me ge pa nt O D T ( P R N) i n partici pa nt s c o m pare d t o t he 
o bser vati o n peri o d  ( O P). 
2. 3  E x pl or at or y O bjecti ves  
● T o e val uate t he effect of 7 5 m g Ri me ge pa nt O D T treat me nt c o m pare d t o baseli ne o n 
t he 1 4 -Ite m Mi grai ne-S pecific Q ualit y of Life Q uesti o n naire v 2. 1 ( M S Q o L Q ). 
● T o e val uate t h e effect of 7 5 m g Ri me ge pa nt O D T treat me nt o n t he Mi grai n e Prefere n ce 
of Me dicati o n ( P o M) . 
● T o e val uate t he effect of 7 5 m g Ri me ge pa nt O D T treat me nt o n t he Satisfacti o n wit h 
Me dicati o n ( S M) s ur ve y. 
● T o e val uate t he effect of 7 5 m g Ri me ge pa nt O D T treat me nt c o m pare d t o baseli ne o n 
t he Mi grai ne Disa bilit y Assess me nt ( MI D A S). 
● T o e val uate t he effect of 7 5 m g Ri me ge pa nt O D T treat me nt o n t he Cli nical Gl o bal 
I m pr essi o n-c h a n ge ( C GI -c) scale. 
3  
St u d y Desi g n  
3. 1  O ver all Desi g n  
T his will be a m ulti -ce nter, o pe n -la bel, l o n g-t er m safet y st u d y of B H V 3 0 0 0 f or t he treat me nt 
of ac ute mi grai ne i n C hi nese partici pa nt s t o pr o vi de t he l o n g-ter m safet y data i n C hi nese 
partici pa nt s t o bri d ge t he e xisti n g c o m pre he nsi ve cli nical trial data of 7 5 m g Ri me ge pa nt i n 
mi grai ne. A p pr o xi matel y 2 4 0 a d ult partici pa nt s wit h mi grai ne were pla n ne d t o be e nr olle d t o 
recei v e 7 5 m g of Ri me ge pa nt O D T ( P R N use, u p t o 1 ta blet per da y).  
T he scree ni n g peri o d will be c o nsiste d of a s cree ni n g visit a n d a 3 0 -da y O P . Partici pa nt s m ust 
ha ve a hist or y of 6 t o 1 8 m o derate t o se vere mi grai ne attac ks per m o nt h wit hi n 3 m o nt hs pri or 
t o t he Scree ni n g Visit i n or der t o meet t he e nteri n g criteria of t his st u d y.  
U p o n t he c o m pleti o n of t he scree ni n g visit, partici pa nt s will be pr o vi de d a n electr o ni c diar y 
(e Diar y) t o d oc u me nt eac h da y if a mi grai n e occ urs, t he i nte nsit y of eac h mi grai ne attac k a n d 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 0  of 3 6  
 
 
if t he mi grai ne is treate d f or t h e 3 0-d a y O P . P artici pa nt s will rec or d t he sta n dar d of care 
mi grai ne treat me nt recei ve d via b ri n g y o ur o w n d e vice (B Y O D ). After c o m pleti n g t he 3 0-da y 
O P , t he partici pa nt  will ret ur n t o t he cli nic wit h b ot h rec or ds f or t he Bas eli ne Visit. At t he 
Baseli ne Visit, eli gi bilit y f or c o nti n ue d p artici p ati o n i n t he st u d y will be assesse d, a n d 
eli gi bilit y will be deter mi ne d as m uc h as p ossi ble pri or t o dis pe nsi n g st u d y dr u g, partici pa nt  
nee d ha ve least 6 mi grai ne da ys d uri n g t he 3 0 -da y O P  t o be eli gi ble a n d w o me n of c hil d beari n g 
p ote ntial ( W O C B P) m ust ha ve a ne gati ve pre g n a n c y test res ult pri or t o dis pe nsi n g st u d y dr u g. 
After t he i n vesti gat or re vie ws t he res ults of t he bas eli ne la b orat or y assess me nts a n d deter mi nes 
t he partici pa nt ’s c o nti n u e d eli gi bilit y, t he site staff will i nf or m t h e partici pa nt  w het her or n ot 
he/s he is eli gi ble t o start d osi n g i n t he L T T P hase. If eli gi ble f or t he L T T , partici pa nt s will be 
i nstr ucte d t hat t he y ca n ta ke st u d y me dicati o n at t he o nset of a mi grai ne ( of mil d t o se vere 
i nte nsit y). Partici pa nt s will be i nstr ucte d t hat t he y ca n t a ke a ma xi m u m of o ne ta blet of 
Ri me ge pa nt per cale n dar da y d uri n g t he 5 2 -wee k L T T P hase  at t he o nset of a mi grai ne ( of mil d 
t o se vere i nte nsit y).  
Partici pa nt s are re q uire d t o rec or d t heir mi grai ne occ urre n ce a n d se verit y i n t he e Diar y, t o 
rec or d all st u d y me dicati o n d oses via B Y O D. Partici pa nt s are als o re q uire d t o c o nti n ue t o 
rec or d t he st a n dar d of care mi grai ne tr eat me nt t a ke n via B Y O D. Partici pa nt s will als o use 
B Y O D t o c o m plete t h e P o M q uesti o n naire a n d t he S M q uesti o n naire at s pecifie d st u d y 
ti me p oi nts.  
At selecte d st u d y visits, partici pa nt s will c o m plete or will be a d mi nistere d t h e M S Q o L Q v  2. 1 , 
t he MI D A S, a n d C GI-c s cale.  
Pr oce d ures i ncl u de st u d y pers o n nel re vie w of t he e Diar y a n d B Y O D wit h t he partici pa nt , 
assess me nt of st u d y me dicati o n c o m plia nce, m o nit ori n g of t olera bilit y a n d safet y (i ncl u di n g 
vital si g ns, la b orat or y tests, a n d electr o car di o gra p h y). St u d y visits will be a p pr o xi matel y e ver y 
4 wee ks u ntil Wee k 1 6 a n d t he n e ver y 1 2 wee ks f or o n -site visits + e ver y 4 wee ks p h o ne calls 
i n bet wee n e v er y t w o o n site visits u ntil Wee k 5 2.  
Partici pa nt s will ret ur n t o t he st u d y site at t h e e n d of Wee k 5 2 ( ± 7 d a ys) f or t h e E n d of 
Treat me nt Visit. T here is a F oll o w -u p Visit 1 4 da ys ( ± 2 da ys) after t he 
Wee k 5 2/ E arl y 
Ter mi nati o n  Visit.  
T he o verall st u d y desi g n sc he matic is s h o w n i n Fi g ure 1.  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 1  of 3 6  
 
 
Fi g ure 1  St u d y Desi g n  
 
3. 2  R a n d o miz ati o n  
N ot a p plica ble.  
3. 3  Bli n di n g  
T his st u d y is a si n gle -ar m trial . B li n di n g a n d u n bli n di n g met h o ds are n ot a p plica ble.  
3. 4  S a m ple Size C alc ul ati o n  
T he sa m ple size f or t his st u d y is pri maril y base d o n hist orical data, c o nsi deri n g t he safet y  
e val uati o n a n d esti mati o n precisi o n f or t he sec o n dar y e n d p oi nt.  F or t he s ec o n dar y e n d p oi nt of 
c ha n ge fr o m o bser vati o n  p eri o d i n t he n u m ber of mi grai ne  da ys per m o nt h fr o m Wee k 9 -1 2 i n 
partici pa nts treate d wit h ri me ge pa nt, d ata fr o m pr e vi o us l o n g-ter m mi gr ai ne st u d y B H V 3 0 0 0-
2 0 1  s h o we d: 
● 
8 4 8 partici pa nt s wit h a hist or y of 6-1 8 da ys of mi grai ne wit hi n 3 m o nt hs pri or t o 
baseli ne . 
● 
Mea n ( sta n dar d de viati o n, S D) baseli ne mi grai ne da ys: 9. 9 2 ( 3. 0 9 ). 
● 
Mi grai ne da ys mea n ( S D) Wee ks 9 -1 2: 8. 8 4 ( 4. 9 7) . 
● 
C ha n ge fr o m baseli ne i n mea n ( S D) n u m ber of mi grai ne da ys at wee ks 9 -1 2: -1. 0 8 
( 4. 7 4). 
Base d o n t h e a b o v e hist orical trial data res ults  a n d a t distri b uti o n ass u m pti o n , i n t his si n gle-
ar m st u d y, 2 0 5 e val u a ble partici pa nts will pr o vi de a 9 0 % p o wer t o o bser ve a n e gati ve  c ha n g e 
fr o m baseli ne i n mi grai ne da ys at Wee ks 9 -1 2  f or a 1 -si de d 2. 5 % si g nifica nce le vel , a n d fi nall y 
2 3 3 partici pa nt s are re q uire d  t o b e i ncl u de d c o nsi d eri n g 1 2 % dr o p o ut rate b ase d o n B H V 3 0 0 0-
2 0 1 trial.  C o nsi deri n g ot her p ossi ble dat a l oss, a p pr o xi matel y 2 4 0 partici p a nts will be fi nall y 
Scree
ni n g 
visit  
3 0 Da y 
O bser vati o n 
P hase  
Baseli
n e 
Visit  
C o ntact Patie nt 
I nf or m patie nt 
of eli gi bilit y t o 
start d osi n g 
wit h st u d y 
me dicati o n or 
i n eli gi bilit y f or 
st u d y 
5 2 -wee k 
Treat me nt  
E n d of 
Treat me nt 
or Earl y 
D/ C Visit  
1 4 da ys +/ - 2 
da ys  
F oll o w 
u p  Visit  
Dis p e nse 
st u d y me d 
Start 
Treat m
e nt 
St o p  
Treat
me nt  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 2  of 3 6  
 
 
e nr olle d.  
I n t he case of 2 4 0 partici pa nts, if t he a d verse e ve nt rate is 5 % a n d 1 %, t he n t he pr o ba bilit y of 
o bser vi n g at least o ne a d verse e v e nt is  > 9 9. 9 % a n d 9 1. 0 %, res pecti vel y, t h us pr o vi di n g  
s ufficie nt i nf or mati o n f or safet y a n d t olera bilit y assess me nt after L T T wit h 7 5 m g  ri me ge pa nt 
O D T i n C hi nese partici pa nts t o bri d ge t he a vaila ble c o m pre he nsi ve cli nical trial  data of 
ri me ge pa nt 7 5 m g i n t he treat me nt of mi grai ne. 
4  
St u d y E n d p oi nts  
4. 1  Pri m ar y E n d p oi nts  
● A d verse e ve nts , c o m m o n A E s (i nci de nce ≥ 5 %), seri o us a d verse e v e nts  ( S A E), 
a d verse e ve nts lea di n g t o st u d y dr u g disc o nti n uati o n,  etc.; E C G,  vital  si g ns/ p h ysical 
meas ure me nts a n d cli nic al la b orat or y test a b n or m alities . 
4. 2  Sec o n d ar y E n d p oi nt  
● C ha n ge fr o m O bser vati o n Peri o d i n t he n u m ber of mi grai ne da ys b y t otal a n d m o derat e  
or se vere pai n i nte nsit y f or e ver y 4 -wee k i nter val a n d o verall peri o d d uri n g l o n g -ter m 
treat me nt wit h 7 5 m g ri me ge pa nt O D T. 
4. 3  E x pl or at or y E n d p oi nts  
● C ha n ge fr o m bas eli ne i n res ults assesse d wit h t he 1 4 -ite m M S Q o L Q versi o n 2. 1 
f oll o wi n g treat me nt wit h 7 5 m g ri me ge pa nt O D T. 
● Perce nta g e of partici pa nts i n eac h of 3 prefere n ce cate g ories of t he assess m e nt wit h  
Mi grai ne P o M f or mi grai ne f oll o wi n g treat me nt wit h 7 5 m g ri me ge pa nt O D T . 
● Perce nta g e of partici pa nts i n eac h of 7 s atisfacti o n cate g ories of t he S M s ur ve y 
f oll o wi n g treat me nt wit h 7 5 m g ri me ge pa nt O D T. 
● C ha n ge fr o m bas eli ne i n t otal sc ore of t he MI D A S f oll o wi n g treat me nt wit h 7 5 m g 
ri me ge pa nt O D T. 
● Perce nta g e of partici pa nts i n eac h of 7 cate g ories of t he C GI -c s cale after tr eat me nt wit h  
7 5 m g ri me ge pa nt O D T.   
5  
S T U D Y H Y P O T H E SI S  
T he statistical a nal ysis is mai nl y descri pti ve, a n d n o f or mal h y p ot hesis test i n g will be 
perf or me d . 
6  
A N A L Y SI S S E T S  
T he f oll o wi n g  a nal ysis sets will be deter mi ne d  : 
● Scree ne d partici pa nts  set: All partici pa nt s w h o si g n t he i nf or me d c o nse nt. It will be 
use d f or t he a nal ysis of p artici pa nt dis p ositi o n.  
● E nr oll e d partici pa nts  set: Partici pa nt s wit h a n a vaila ble date c ollect e d i n t he C R F o n 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 3  of 3 6  
 
 
w hic h t he i n vesti gat or j u d ges t hat t he y ca n be e nr olle d a n d n otifies of t heir eli gi bilit y 
t o start ta ki n g t he i n vesti gati o nal pr o d uct b y p h o n e.  It will be use d f or t he a nal ysis of 
partici pa nt dis p ositi o n  a n d dr u g acc o u nt a bilit y . 
● F ull a nal ysis set ( F A S): All partici pa nt s w h o are e nr olle d a n d recei ved  at least o ne d ose 
of t he i n vesti gati o nal pr o d uct . It will be use d f or t h e a nal ysis of bas eli ne c haracteristics, 
as well as t he a n al ys es of e x pl orat or y e n d p oi nt meas ures. 
● Efficac y a nal ysis set ( E A S): All partici pa nts i n t he F A S wit h ≥ 1 4 e Diar y da ys  ( n ot 
necessaril y c o nsec uti ve) i n b ot h t he O P a nal ysis peri o d a n d ≥ 1 m o nt h ( 4 -wee k i nter val) 
of t he L T T a n al ysis peri o d . T he E A S will be use d t o assess t he sec o n d ar y e n d p oi nt. 
● Safet y a n al ysis set ( S S): 
All partici pa nt s 
w h o recei ved  at least o ne d ose of 
i n vesti gati o nal pr o d uct. T he S S will be use d f or  safet y a nal yses d uri n g treat me nt safet y 
peri o d . 
● F oll o w -u p safet y a nal ysis set ( F U S S): A ll partici pa nts i n t he S S wit h  last c o ntact date 
(see Secti o n 7. 2. 3 ) i n t he f oll o w-u p safet y a nal ysis peri o d. T he F U S S  will be  use d f or 
f oll o w-u p safet y a nal yses . 
7  
S T A TI S TI C 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  
7. 1  Ge ner al Met h o ds  
All rele va nt data of all partici pa nt s e ntere d i nt o t he data base will be i ncl u de d i n t he partici pa nt  
data listi n gs. U nless ot her wise s pecifie d, partici p a nt  listi n gs will be or dere d b y site, partici pa nt  
I D, a n d ot her v aria bles (e. g., ti me p oi nt). T he listi n gs will i n dicate t he site-partici pa nt  I D. 
F or cate g orical vari a bles, a s u m mar y ta ble of t he n u m ber a n d perce nt a ge of partici pa nt s i n eac h 
cate g or y will be prese nt e d, a n d t he cate g or y of missi n g data will be pr o vi d e d. F or c o nti n u o us 
varia bles, t he descri pti ve statistics of n (e. g., n u m ber of p artici pa nt s), mea n, me dia n, S D, 
mi ni m u m, a n d ma xi m u m , etc. will be prese nte d. T he mi ni m u m a n d ma xi m u m val ues will be 
e x presse d wit h t he sa me precisi o n as t he data. T he mea n a n d me dia n val ues will be e x presse d 
wit h t he data precisi o n pl us o ne deci mal place. S D will be e x presse d wit h t he data precisi o n 
pl us t w o deci mal places. I n ge n eral, all s u m mar y statistics will be re p orte d wit h a ma xi m u m of 
f o ur deci mal places. 
T he 9 5 % c o nfi de nce i nter val ( C Is) will be calc ulate d f or t hese e n d p oi nts: 1) T w o -si de d 9 5 % 
CIs base d o n n or m al distri b uti o n will be calc ulate d f or  c o nti n u o us e n d p oi nts , i ncl u di n g 
mi grai ne da ys, M S Q o L Q , a n d MI D A S . 2) T w o -si de d e xact C l o p per-P ears o n CIs will be 
calc ulate d f or P o M , S M, a n d C GI -c.  
F or t he safet y data a n d t he efficac y data c ollect e d i n t he C R F, u nless ot her wise s pecifie d, 
baseli ne will be  t he last n o n-missi n g assess me nt data pri or t o or o n t he da y of first d ose. F or 
t he efficac y data c ollecte d i n t he e Diar y, baseli ne will be  calc ulate d base d o n t he data f r o m t he 
o bser vati o n a nal ysis peri o d.  
S A S ®  ( Versi o n 9. 4) will be use d t o perf or m all statistical calc ulati o ns a n d ge nerate ta bles, 
listi n gs, a n d fi g ures.  
7. 2  D at a Pr ocessi n g R ules  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 4  of 3 6  
 
 
7. 2. 1  Ha n dli n g of Missi n g Data  
Missi n g o bser ve d val ues  
U nless ot her wise s pecifie d, all data  will be base d o n t he act ual meas ure me nt data.  
Missi n g dates  
F or i nc o m plete date d ata, t he dates i n t he listi n gs will be prese nt e d acc or di n g t o t he act ual 
sit uati o n. 
If t he st art dat e of a n y A E or pri or/ c o nc o mita nt m e dicati o n is missi n g, t he f oll o wi n g r ules will 
be a p plie d:  
● If t he start d ate is c o m plet el y missi n g, it will be i m p ute d wit h t he first d ose d ate  of st u d y 
dr u g. H o we ver, if t he e n d date is n ot missi n g a n d occ urs pri or t o t he first d ose of st u d y 
dr u g, t he start date will be re place d wit h t he  earliest of n o n -missi n g e n d date or 
i nf or me d c o nse nt dat e.   
● If t he start m o nt h a n d da y are missi n g b ut t he start year is a vaila bl e, t he start date will 
be i m p ute d wit h t he first da y ( Da y 1) of t he first m o nt h (Ja n uar y). H o we ver, if t he year 
is t he sa me as t hat of t he first d ose of st u d y dr u g, t he start date will be t he sa me as t he 
date of t he first d ose of st u d y dr u g.  
● If t he start da y is missi n g b ut t he start year a n d m o nt h are a v aila ble, t he st art date will 
be i m p ute d wit h t he first da y ( Da y 1) of t he m o nt h. H o we v er, if t he start year a n d m o nt h 
are t h e sa me as t h ose of t he first d ose of st u d y dr u g, t he start d ate will be t he sa me as 
t he date of t he first d ose of st u d y dr u g.  
If t he e n d date of a n y A E or pri or/c o n c o mita nt me dicati o n is missi n g, t he f oll o wi n g r ules will 
be a p plie d:  
● F or A E  if t he e n d dat e is c o m pletel y missi n g, t he e n d date will be t he latest of t he 
partici pa nt wit h dra wal/c o m pleti o n date, deat h date, last acti ve da y of st u d y dr u g, or 
start date. F or pri or /c o nc o mita nt me dicati o n wit h c o m pletel y missi n g e n d date a n d is 
n o l o n ger a d mi nistere d, t he e n d date will be i m p ute d f oll o wi n g a b o ve  r ule f or A E wit h 
c o m pletel y missi n g e n d date . Ot her wis e , t he e n d date will n ot be i m p ute d. 
● If t he e n d m o nt h a n d da y are missi n g b ut t he e n d year is a vaila bl e, t he e n d date will be 
i m p ute d wit h t he last da y of t he last m o nt h ( Dece m ber). H o we ver, if t h e e n d year is t he 
sa me as t hat of t he c o m pleti o n/ wit h dra wal date, t he e n d date will be t he sa me as t he 
d ate of c o m pleti o n/ wit h dra wal.  
● If t he e n d da y is missi n g b ut t he e n d year a n d m o nt h are a vaila bl e, t he e n d date will be 
i m p ute d wit h t he last da y of t he m o nt h. H o we v er, if t he e n d y ear a n d m o nt h are t he 
sa me as t h ose of c o m pleti o n/ wit h dra wal, t he e n d date will be t he sa me as t he date of 
c o m pleti o n/ wit h dra wal.  
T hese i m p ute d dat es will be use d t o d eter mi ne w het her a n A E or me dicati o n occ urs (is use d) 
d uri n g treat me nt.  
7. 2. 2  Ot her Data Pr o cessi n g R ules  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 5  of 3 6  
 
 
I n t he d escri pti ve s u m maries of safet y e n d p oi nts (e. g., a bs ol ute val ue a n d c h a n ge fr o m bas eli ne 
i n la b orat or y tests, vital si g ns, E C G), if an  assess me nt  is meas ure d t w o or m ore ti mes at a visit, 
t he n t he last data of t he visit will be use d f or a nal ysis. T he assess me nt  res ults of all u nsc he d ul e d 
a n d sc he d ule d visits will be prese nt e d i n t he listi n gs. 
7. 2. 3  Deri ve d D ates  
St u d y Da y s 
Refer t o Pr ot oc ol Secti o n 4. 3 f or t he sc he d ul e of assess me nts. St u d y Da ys are cal c ulate d fr o m 
t he L T T start date as f oll o ws :   
● Assess me nt/e ve nt date / e Diar y refere nce date –  L T T start  d ate + 1, if t he 
assess me nt/e ve nt date ≥ L T T start  Date ; 
● Assess me nt/e ve nt date /e Diar y refere nce date –  L T T start  d ate, if t h e assess me nt/e ve nt 
date  < L T T start  Date , w here 
L T T start d ate is defi n e d as earlier of ( 1) Baseli ne Visit date, or ( 2) st u d y dr u g start d ate 
(see als o i n Secti o n 7. 2. 4 ).  
Treat me nt D a ys  
Treat me nt  da ys are calc ulate d fr o m t he st u d y dr u g start date as f oll o ws:  
● Assess me nt/e ve nt date –  st u d y dr u g start date + 1, if t he assess me nt/e ve nt d ate ≥ st u d y 
dr u g start date.  
● Assess me nt/e ve nt date –  st u d y dr u g start date, if t he assess me nt/e ve nt date < st u d y dr u g 
start date. 
T he T reat me nt D a y will be  dis pla ye d t o get her wit h S t u d y D a y i n t he i n di vi d ual partici pa nts 
listi n gs. 
e Diar y Da ys  
A n e Diar y d a y is defi ne d as a da y wit h a c o m plete e Diar y refere n ce dat e  bas e d o n  a n y q uesti o n 
fr o m t he e ve ni n g re p ort h ea dac he l o g or f oll o w u p l o g (see ste p b.i v i n A p pe n di x : t he deri vati o n 
of mi grai ne da y ). 
Last C o ntact D ate  
T he last c o nta ct date is use d t o deter mi ne s elect p ara meters (i.e., ti me o n st u d y, i m p ute d n o n -
st u d y me dicati o n e n d dat es), a n d is t y picall y defi n e d usi n g n o n-i m p ute d dates as f oll o ws: 
1.  Earliest c o m plete deat h date fr o m all s o urces t hat c ollect deat h dates (e. g., Deat h C R F), 
if it e xists. 
2.  Ot her wise, t he ma xi m u m c o m plete date of t he f oll o wi n g C R F or e xter nal data s o urces, 
as a p plica ble: A E start or e n d; E C G; e Diar y assess me nt; i nf or me d c o nse nt; la b orat or y 
test c ollecti o n; n o n-st u d y me dicati o n start or e n d; p h ysical e xa m; pr ot oc ol de viati o n; 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 6  of 3 6  
 
 
q uesti o n naire ; rati n g scale; st u d y i nter ve nti o n start or e n d; partici pa nt dis p ositi o n 
c o m pleti o n/ disc o nti n uati o n; visit; vital si g ns . 
7. 2. 4  A nal ysis Peri o d s 
T o  facilitate t he a n al yses base d o n e Diar y data (i ncl u di n g e Diar y c o m plia nce a n d mi grai ne 
da ys) , t he a n al yses f or s afet y e n d p oi nts, the f oll o wi n g a nal ysis peri o ds will be  defi ne d .  
T a ble 1 . A n al ysis Peri o ds 
A nal ysis peri o ds  
Start date/ ti me 
E n d date/ ti me 
Us a ge 
O P  
Scree ni n g Visit date  
L T T start date –  1 da y  
T o be u se d t o calc ulate 
t he e Diar y c o m plia nce, 
n u m ber of mi grai ne da ys 
per 4 wee ks i n t his 
peri o d.  
L T T  
Earlie r of ( 1) 
Baseli ne Visit date, 
a n d  ( 2) stu d y dr u g 
start date  
Later  of ( 1) Wee k 
5 2/ E O T  date, a n d ( 2) 
st u d y dr u g last d ose date  
 
T o be u se d t o calc ulate 
t he e Diar y c o m plia nce  
a n d n u m ber of mi grai ne 
da ys  per 4 wee ks  or t he 
o verall peri o d  i n t he 
l o n g-ter m treat me nt. 
Pre -treat me nt safet y 
 
St u d y dr u g start date –  1 
da y f or A E s; st u d y dr u g 
start date/ti me ot her wise  
T o be u se d t o assess t he 
safet y e n d p oi nts pri or t o 
st u d y dr u g treat me nt. 
Treat me nt safet y 
St u d y dr u g start date 
f or AE s; after st u d y 
dr u g start date /ti me 
ot her wise  
[Later of ( 1) Wee k 
5 2/ E O T  date, a n d ( 2) 
st u d y dr u g last d ose d ate] 
+ 7 da ys   
T o be u se d t o assess t he 
safet y e n d p oi nts of t he 
treat me nt peri o d.  
F oll o w -u p safet y 
[Later of ( 1) Wee k 
5 2/ E O T date, a n d 
( 2) st u d y dr u g last 
d ose date ] + 8  da ys  
 
T o be use d t o assess t he 
safet y e n d p oi nts of t he 
f oll o w-u p peri o d.  
 
7. 2. 5  A nal ysis Visit Wi n d o ws  
Acc or di n g t o Secti o n 4. 3 of t he pr ot oc ol, t he a nal ysis visit wi n d o ws f or efficac y a n al yses  will 
be defi ne d . A nal ysis wi n d o ws f or t he sec o n d ar y en d p oi nt will be defi ne d wit hi n t he O P a n d 
L T T a nal ysis peri o d s t hat are defi ne d i n Secti o n 7. 2. 4  ( See Ta ble 2 Ta bl e 2 ). T he calc ulati o n of 
n u m ber of mi grai ne da ys will be base d o n t he st u d y da y as defi ne d i n Secti o n Err or! Refere nce 
s o urce n ot f o u n d.7. 2. 3 . A nal ysis wi n d o ws f or t he e x pl or at or y e n d p oi nts will be defi ne d 
directl y as bel o w i n Ta bl e 3 Ta ble 3 .   
T a ble 2 . A n al ysis Wi n d o ws f or Mi gr ai ne D a ys 
Per 4 -wee k I nter v al  
A nal ysis Wi n d o w i n t he L T T A nal ysis Peri o d  
(St u d y D a y ) 
M o nt h 1: Wee k 1 t o Wee k 4  
1 -2 8  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 7  of 3 6  
 
 
M o nt h 2: Wee k 5 t o Wee k 8  
2 9 -5 6  
M o nt h 3: Wee k 9 t o Wee k 1 2  
5 7 -8 4  
M o nt h 4: Wee k 1 3 t o Wee k 1 6  
8 5 -1 1 2  
M o nt h 5: Wee k 1 7 t o Wee k 2 0  
1 1 3 -1 4 0  
M o nt h 6: Wee k 2 1 t o Wee k 2 4  
1 4 1 -1 6 8  
M o nt h 7: Wee k 2 5 t o Wee k 2 8  
1 6 9 -1 9 6  
M o nt h 8: Wee k 2 9 t o Wee k 3 2  
1 9 7 -2 2 4  
M o nt h 9: Wee k 3 3 t o Wee k 3 6  
2 2 5 -2 5 2  
M o nt h 1 0: Wee k 3 7 t o Wee k 4 0  
2 5 3 -2 8 0  
M o nt h 1 1: Wee k 4 1 t o Wee k 4 4  
2 8 1 -3 0 8  
M o nt h 1 2: Wee k 4 5 t o Wee k 4 8  
3 0 9 -3 3 6  
M o nt h 1 3: Wee k 4 9 t o Wee k 5 2  
3 3 7 -e n d of L T T  
T a ble 3 . A n al ysis Wi n d o ws f or M S Q o L Q , MI D A S , P o M, S M, a n d C GI -c Sc ale  
Sc he d ule d V isits *  
Tar get D a y  
(B ase d o n  St u d y D a y ) 
A nal ysis  W i n d o w  
(St u d y D a y ) 
Baseli ne  
1  
Pri or t o or o n t he first d ose date  
Wee k 1 2  
8 4  
7 1 -9 8  #  
Wee k 2 8  
1 9 6  
1 8 3 -2 1 0 #  
Wee k 4 0  
2 8 0  
2 6 7 -2 9 4  #  
Wee k 5 2  
3 6 4  
3 5 1 - e n d of L T T  
Earl y Ter mi nati o n  
T he Earl y Ter mi nati o n Visit or last p ost -baseli ne 
q uesti o n naire fr o m t he earl y ter mi nate d partici p a nts  
* T he P o M, S M, a n d C GI -c scale will n ot be c ollecte d at baseli ne , Wee k 1 2 a n d Wee k 4 0 .  
#  F or earl y ter mi nate d partici pa nts, t he 
Wee k X wi n d o w e n d date will be t he mi ni m u m of ( 1) Earl y 
Ter mi nati o n Date -1 da y  or ( 2)  Wee k X a nal ysis wi n d o w  e n d date , w here X is t he last Wee k wit h Tar get 
Da y bei n g pri or t o Earl y Ter mi nati o n Date.  
 
I n Err or! Refere nce s o urce n ot f o u n d. Ta ble 3 , if t here are m ulti ple n o n -missi n g val ues  fall 
i nt o a sa me a n al ysis wi n d o w s, t he n t he f oll o wi n g al g orit h m will be ta ke n t o i de ntif y t he val ue  
f or a nal ysis: 
1.  T he  val ue cl os est t o t he tar get da y  f or t he visit will be  use d .  
2.  If t he o bser vati o ns are wit h e q ual dista nce fr o m t he tar get da y i n a bs ol ute val ue, t he 
o ne wit h c orrect n o mi nal visit la bel will be use d. F or e xa m ple, if t w o o bser vati o ns fall 
i nt o t he a nal ysis wi n d o w f or W ee k 2 8 Visit o n St u d y Da ys 1 9 0 a n d 2 0 2, res pecti vel y, 
t he o bser vati o n t hat is rec or de d as W ee k  2 8  will b e use d.  
3.  If neit her 1 n or 2 ca n i d e ntif y t he o bser vati o n, t he n t he last val ue meas ure d is use d. 
A ll o bser v atio n s wi ll, h o we v er,  be  in clu de d  i n the  listin g s. 
7. 3  St u d y P artici p a nt s 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 8  of 3 6  
 
 
7. 3. 1  Partici pa nt  Dis p ositi o n  
A partici pa nt  dis p ositi o n s u m mar y ta ble will be pr o vi de d  base d o n s cree ne d partici pa nt s. T he 
f oll o wi n g cate g ories will be s u m marize d i n t his ta ble: 
● Scree ne d p artici pa nt s 
● Scree n fail ures a n d reas o ns f or scree n fail ure  
● E nr olle d partici pa nt s 
o  Treate d p artici pa nt s 
▪ Partici pa nts w h o c o m plet e d  t he treat me nt  
▪ Partici pa nts w h o disc o nti n ue d  treat me nt a n d reas o ns  
▪ Partici pa nts w h o c o m plet e d  t he st u d y  
▪ Partici pa nts w h o disc o nti n ue d  st u d y a n d reas o ns  
o  U ntreate d p artici pa nt s 
● N ot e nr olle d b ut t reat e d  
 
I n a d diti o n, t he n u m ber a n d perce nta ge of partici p a nt s i n eac h a nal ysis set will be s u m marize d  
a n d liste d base d o n scree ne d partici pa nts. 
7. 3. 2  Pr ot oc ol De viati o ns  
Base d o n t he F A S , p arti ci pa nt s wit h i m p orta nt pr ot oc ol de viati o ns ( P D) will be s u m marize d 
acc or di n g t o t h e classifi cati o n of P Ds , wit h t he n u m ber a n d p erce nta ge of cas es cal c ulate d. 
Partici pa nt s wit h P D  will be liste d i n detail.  
D uri n g t he st u d y c o n d uct , P D re p orti n g was u p dat e d  per Ti ger Me d’s latest S O P. P D cate g ori es 
w ere c ha n g e d fr o m M aj or/ Mi n or P D s t o I m p ort a nt/ N o n-i m p orta nt P Ds. T he pre vi o us maj or 
P D cate g ories will be c o n verte d t o I m p orta nt P D cate g ories b ase d o n me di cal re vie w . F or  t he 
mi n or  P D s, if t he P Ds were d ue t o C O VI D -1 9, t he  cate g ories of t hese mi n or P Ds will be 
c o n verte d t o n o n -i m p ort a nt P D cate g ories b ase d o n  me dical re vie w ; if t he P Ds were n ot d ue t o 
C O VI D -1 9, mi n or P D cate g ories will be ke pt a n d will n ot be c o n verte d t o n o n -i m p orta nt P D 
cate g ories. I m p orta nt P Ds a n d P Ds d ue  t o C O VI D-1 9 will be s u m mari ze d base d  o n t he ne w 
P D cate g ories . Listi n gs of P Ds will be pr o vi de d wit h t he ne w P D cate g ories ( I m p orta nt/ N o n-
i m p orta nt) a n d t he pre vi o us P D cate g ories ( Maj or/ Mi n or). See A p pe n di x: Ma p pi n g R ule of P D 
Cate g ori es. 
T he det ails a n d s e verit y of P D s will be e v e nt uall y d eter mi ne d at t he data re vi e w meeti n g bef ore 
data base l oc k.  
7. 3. 3  De m o gra p hics/ Baseli ne C haracteristics  
T he de m o gra p hics a n d b aseli ne c haract eristics will be descri pti vel y s u m marize d b ase d o n t he 
F A S  usi n g t he met h o d descri be d i n Secti o n 7. 1 , i ncl u di n g: 
● 
A ge, ge n der , et h nicit y , w ei g ht ( k g), hei g ht (c m), b o d y mass i n de x ( B MI ; k g/ m 2), a n d 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 1 9  of 3 6  
 
 
hist or y of aller g y ( yes, n o ). 
A ge at i nf or me d c o nse nt will be calc ulate d.  A ge (i n years) a n d B MI will be s u m marize d as a 
c o nti n u o us varia ble , a n d b y cate g ories wit h n u m bers a n d perce nta ges . A ge w ill be cate g orize d 
as < 6 5  vs. ≥6 5 . B MI will be cate g orize d as < 2 5 vs. ≥2 5 t o < 3 0 vs. ≥ 3 0.    
T he de m o gra p hi cs a n d b aseli ne c haracteristics  will be liste d . 
7. 3. 4  Mi grai ne Hist or y  
T he mi grai ne hist or y  will be descri pti vel y s u m marize d acc or di n g t o t he met h o d descri be d i n 
Secti o n 7. 1  a n d be liste d base d o n t he F A S, i ncl u di n g:  
● 
A ge a t mi grai ne o nset , di d t he partici pa nt e x perie nce mi grai nes f or at least o ne year 
pri or t o scree ni n g  ( yes vs n o ), mi grai ne hist or y ( years), a v era g e d urati o n of u ntreate d 
mi grai ne attac ks ( h o urs ), n u m ber of m o derat e t o se vere mi grai nes per m o nt h wit hi n 
last 3 m o nt hs, pri mar y mi grai ne t y pe  ( mi grai ne wit h or wit h o ut a ura), mi grai ne 
s y m pt o ms (hea dac he attac ks lasti n g 4 -7 2 h o urs, u nilateral l ocati o n, p ulsati n g q ualit y, 
m o derate or s e vere p ai n i nte nsit y, 
e x perie nce na useas a n d/ or v o miti n g d uri n g 
hea dac he , e x perie nce p h ot o p ho bia a n d/ or  p h o n o p h o bia  d uri n g hea dac he ), 
A ura 
s y m pt o ms (vis ual , se ns or y, speec h a n d/ or la n g ua ge , m ot or, brai nste m, reti nal, ot her 
s y m pt o ms). 
7. 3. 5  Me dical H ist or y 
T he me dical hist or y will be c o de d usi n g t he latest versi o n of Me dical Di cti o nar y f or Re g ulat or y 
Acti vities ( Me d D R A  Versi o n  2 5. 0 ). 
T he n u m ber  a n d perce nta ge of partici pa nt s wit h at least o ne me dical hist or y  will be s u m marize d 
b y S yste m Or ga n Class ( S O C) a n d Preferre d T er m ( P T) bas e d o n t h e F A S. F or eac h p artici pa nt, 
m ulti ple me dical hist ories of t he sa me S O C or P T will be c o u nte d o nl y o nce wit hi n eac h S O C 
a n d P T. Ta bles will be prese nte d i n des ce n di n g or der bas e d o n fre q ue nc y of eac h S O C , a n d 
t he n i n desce n di n g or der base d o n fre q ue nc y of eac h P T wit hi n a  S O C.  
Me dical hist ories will be liste d b y partici pa nts . 
7. 3. 6  Pri or a n d C o nc o mita nt Me dicati o ns  
S u m mar ies will be perf or me d base d o n t he S S . 
N o n -st u d y dr u gs will be c o de d i nt o A nat o mical T hera pe utic C he mical Classificati o n S yste m 
( A T C) c o d es a n d preferre d dr u g na m es usi n g t he W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y 
(W H O -D D) . F or m ulti ple rec or ds of t he sa me dr u g ta ke n b y a partici pa nt , t he dr u g will be 
c o u nte d o nl y o nce u n d er eac h A T C Gra de 2 ter m a n d/ or P T ite m.  
 T he n o n -st u d y me dicati o n  t y pes i ncl u de: 
● Pri or me dicati o ns, i ncl u di n g pre vi o us a n d c urre nt me dicati o ns  
Pri or me dicati o ns are defi ne d as t h ose ta ke n bef ore st u d y dr u g, i.e., i m p ute d start or e n d 
date < st u d y dr u g start d ate. N ote t hat all n o n -st u d y me dicati o ns are c o nsi dere d pri or 
f or partici pa nts  wit h missi n g st u d y dr u g start d ate. Pri or m e dicati o ns i ncl u de t he 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 0  of 3 6  
 
 
f oll o wi n g s u bt y pes: 
o  Pre vi o us  me dicati o ns, defi ne d as t h ose ta ke n b ef ore  i nf or me d c o nse nt, i.e., 
t h ose wit h a n i m p ute d start or e n d date < i nf or me d c o nse nt date . 
o  C urre nt me dicati o ns, defi ne d as t h ose ta ke n o n or after i nf or me d c o ns e nt 
a n d bef ore st u d y dr u g. 
•  C o nc o mita nt me dicati o ns, defi ne d as t h ose ta ke n wit h  st u d y dr u g. 
S u m maries  will be pr o vi de d f or: c urre nt pr o p h ylactic mi grai ne me dicati o ns, c o nc o mita nt 
pr o p h ylactic 
mi grai ne 
me dicati o ns, c urre nt 
m e dicati o ns, a n d c o nc o mita nt 
me dicati o ns, 
res pecti vel y.   
All n o n -st u d y pre vi o us, c urre nt, a n d c o nc o mita nt me dicati o ns, i ncl u di n g pr o p h ylactic 
mi grai ne me dicati o ns a n d ot her me dicati o ns, will be liste d.  
7. 3. 7  Pri or a n d C o nc o mita nt N o n -dr u g T hera p ies 
N o n -dr u g t hera pies will be cate g orize d i nt o pre vi o us, c urre nt, a n d c o n c o mita nt t hera pies bas e d 
o n t hera p y start/e n d dates usi n g t he sa me criteria as state d i n Secti o n 7. 3. 6  a n d be s u m marize d 
usi n g t he  sa me met h o d as state d i n Secti o n 7. 3. 6 .  
A detaile d listi n g of n o n -dr u g t hera pies will be pr o vi de d base d o n t he S S . 
7. 3. 8  Dr u g Acc o u nta bilit y a n d e Diar y C o m plia nce  
T he dr u g acc o u nta bilit y will be s u m marize d b y t he f oll o wi n g cate g ories b ase d o n t he e nr olle d 
partici pa nt s usi n g t he met h o d descri be d i n Secti o n 7. 1 : 
● At least o ne kit dis pe nse d    
● Di d n ot ret ur n a n y dr u g  
● E ver l ost or waste d dr u gs   
● A vera g e n u m ber of dis pe nse d  ta blets (ta blets p er m o nt h ) = 4 (wee ks )* (s u m of t otal 
n u m ber  of dis pe nse d a m o u nt  - a m o u nt  dis pe ns e d o n t he l ate st ret ur n dat e) / ((latest 
ret ur n date –  earliest  dis p e nse date ) / 7)  
● A vera g e n u m ber of ret ur ne d ta blets (ta blets per m o nt h) = 4 ( wee ks) * s u m of t otal 
n u m ber of ret ur ne d a m o u nt / ((latest ret ur n dat e –  earliest  dis pe nse  d ate) / 7)  
● A vera g e n u m ber of ta blets l ost  or waste d (ta blets per m o nt h) = 4 ( wee ks) * s u m of t otal 
n u m ber of n ot use d a n d n ot ret ur ne d a m o u nt  / ((l atest ret ur n dat e –  earliest dis pe nse  
date) / 7)  
Dr u g distri b uti o n a n d ret ur n pr ofiles will be liste d. 
T he c o m plia nce of  e Diar y Mi grai ne rec or ds will be s u m mari ze d b y O P a n d L T T a nal ysis 
peri o d base d o n t he S S usi n g t he f oll o wi n g f or m ula:  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 1  of 3 6  
 
 
C o m plia nce i n eac h peri o d = (act ual n u m ber of e Diar y e ntr y da ys  i n t he peri o d / n u m ber of da ys 
i n t he peri o d) *  1 0 0 % , w here n u m ber of da ys i n t he peri o d = a n al ysis peri o d e n d date –  a nal ysi s 
peri o d start  date +  1  da y (see Secti o n 7. 2. 4 ). 
● T he c o m plia nce will be s u m marize d usi n g t he met h o d descri be d i n Secti o n 7. 1 .  
● T he n u m ber a n d p erce nta ge of partici p a nt s wit h ≥ 8 0 %, ≥ 9 0% c o m plia nce will als o be 
calc ulate d.  
A listi n g of t he c o m plia nce will be pr o vi de d . 
7. 4  Effic ac y A n al yses  
Efficac y a nal yses will be base d o n t he F A S , u nless s pecifie d ot her wise. S u m maries  will be 
base d o n t he a n al ysis  visit wi n d o w s (refer t o  Secti o n 7. 2. 5 .).  
7. 4. 1  Efficac y A nal ysis of t he Sec o n dar y E n d p oi nt  
T he n u m ber of mi grai ne da ys (refer t o a p p e n di x : t he deri vati o n of mi grai ne da y) b y t otal a n d 
se verit y of mi grai ne attac ks will be calc ulate d f or t he O P a n d t h e o verall L T T  peri o d as defi n e d 
i n Ta ble 1 Ta ble 1 , a n d eac h  m o nt h  (i.e., 4-wee k i nter val)  as d efi ne d i n Ta ble 2 Ta ble 2 .  
A nal yses will be b ase d o n t he E A S, ie, p artici pa nts  w h o ha v e ≥ 1 4 e Diar y d a ys ( n ot necessaril y 
c o nsec uti ve) wit hi n b ot h t he O P  a nal ysis peri o d a n d at least o ne m o nt h ( 4 -wee k i nter val ) i n t he 
L T T  anal ysis peri o d . F or  t he assess me nt ti me p oi nts, all val ues o bser ve d after ta ki n g sta n dar d 
of care mi grai ne me di cati o ns  (ac ute or pr o p h ylactic) will be use d.   
T he n u m ber of mi grai ne da ys i n O P , per 4 -wee k i n L T T peri o d , a n d o v erall L T T peri o d will 
be pr o rat e d t o 2 8 da ys t o acc o u nt f or da ys wit h missi n g mi grai ne data:  
N u m ber of mi grai ne d a ys i n t he O P  
= 2 8 *(s u m of mi grai ne da ys i n t he o bser vati o n a nal ysis peri o d)  / (s u m of e Diar y da ys i n t he 
o bser vati o n a nal ysis peri o d).   
N u m ber of mi grai ne d a ys per m o nt h (4 -wee k i nter val ) i n t he L T T peri o d  
= 2 8 *(s u m of mi grai ne d a ys wit hi n a 4 -wee k i nter val)  / (s u m of e Diar y  da ys wit hi n t his 4 -wee k 
i nter val).  
O verall L T T  
= 2 8 *(s u m of mi grai ne da ys i n t he L T T a nal ysis peri o d ) / (s u m of e Diar y da ys i n t he L T T 
a nal ysis peri o d.  
N ote t hat, i n t he a b o ve calc ulati o ns, partici pa nts m ust ha ve  ≥1 4 da ys of e Diar y d ata ( n ot 
necessaril y c o nsec uti ve ) i n t he O P, eac h m o nt h ( 4-wee k i nter val) i n t h e L T T peri o d ; all 
partici pa nts i n E A S will be  i ncl u de d i n t he calc ulati o n f or o verall L T T p eri o d.  
Pr orate d  abs ol ute val ues  ( base d o n a b o ve f or m ulas), cha n ge a n d perce nt a g e c ha n ge fr o m O P 
i n mi grai ne da ys per m o nt h  (4 -wee k i nterv al) of L T T peri o d a n d o verall L T T peri o d will be 
s u m marize d descri pti ve l y b y se verit y (t otal; m o derate or se v ere) usi n g t he statistics me nti o ne d 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 2  of 3 6  
 
 
i n Secti o n 7. 1 . F or t he a n al ysis of t he perce nta ge c ha n ge fr o m O P , o nl y partici pa nt s w h o ha ve 
at least o ne mi grai ne d a y (a bs ol ute, n ot pr orat e d t o 2 8 da ys)  of a p pr o priate se verit y i n t he O P  
will be i ncl u de d.  
I n a d diti o n, for eac h 4 -wee k i nter val i n t he L T T  peri o d, t he n u m ber a n d perce nta ge of 
partici pa nt s wit h t he mi grai ne da ys decrease d b y ≥ 2 5 %, ≥ 3 0 % , ≥ 5 0 % , a n d ≥ 6 0 % fr o m t he 
O P  will be s u m marize d  b y se verit y . T he n u m ber a n d perce nt a ge of partici pa nt s wit h t he mea n 
n u m ber of mi grai n e da ys i n t he o verall L T T peri o d decrease d b y ≥ 2 5 %, ≥ 3 0 % , ≥ 50 % , a n d ≥ 
6 0 %  fr o m t he O P  will be s u m marize d  b y se verit y . 
L o n git u di nal  pl ots will dis pla y  t he mea n re d u cti o n i n t he n u m ber of mi grai ne da ys i n t he L T T  
peri o d fr o m t he O P  o n  t he Y-a xis a n d L T T m o nt h  o n  t he X-a xis, b y se verit y. Vertical  bars will 
dis pla y 9 5 % CI . L o n git u di nal pl ots f or t he mea n n u m ber of mi grai ne da ys i n t he L T T peri o d 
will als o be dis pla ye d  usi n g t he sa me f or mat.  
T he n u m ber of mi grai ne da ys i n pr orate d a bs ol ute val ue, c ha n ge fr o m O P, perce nt a ge c ha n g e 
fr o m O P, a n d perce nta g e re d ucti o n cat e g ories will be liste d. 
7. 4. 2  Efficac y A nal ysis of t he E x pl orat or y E n d p oi nts  
Defi niti o n s a n d a nal ysis met h o d s f or t he e x pl or at or y e n d p oi nts are i ntr o d uce d i n t his secti o n.  
Ta bles  will  dis pla y res ults b y a nal ysis visit wi n d o w  as defi ne d i n Secti o n 7. 2. 5 . 
Mi grai ne -S pecifi c Q ualit y of Life Q uesti o n nair e ( M S Q o L Q) V 2. 1  
T his q uesti o n naire has 1 4 ite ms a n d 3 d o mai ns ( Restricti ve R ole F u ncti o n, Pre ve nti ve R ole 
F u ncti o n, a n d E m oti o nal F u ncti o n), a m o n g w hic h Restricti ve R ole F u ncti o n c o nsists of 7 ite ms, 
Pre ve nti ve R ole F u ncti o n c o nsists of 4 ite ms, a n d E m oti o nal F u ncti o n c o nsists of 3 ite ms. A 
6 -p oi nt scale is a d o pte d f or t he a ns wer o pti o ns t o eac h ite m, wit h 1 i n dicati n g t he q ualit y of 
life is n ot da ma ge d (“ N e ver”) a n d 6 i n dicati n g ma xi m u m da ma ge (“ All t he ti me”). First, 
i n di vi d ual ite m sc ores are rec o de d as { 7 –  ori gi nal it e m sc ore }. Ne xt,  t he s u m of t he 
q uesti o n naire res ults of all rec o de d ite ms i n eac h d o mai n will be calc ulate d a n d use d as t he ra w 
sc ore. If i n a p artic ular d o mai n, t he q uesti o n naire res ults of less t ha n or e q ual t o half of t he 
ite ms are missi n g (e. g., t he q uesti o n naire res ults of ≤ 3 Restricti ve R ole F u ncti o n ite ms, ≤ 2 
Pre ve nti ve R ole F u ncti o n ite ms are missi n g, or ≤ 1 E m oti o nal F u ncti o n ite m are missi n g). T he 
ra w sc ore of t he d o mai n will be i m p ute d as t he mea n of t he q uesti o n naire res ults of n o n-missi n g 
ite ms. If i n a partic ular d o mai n, t he q uesti o n naire res ults of m ore t ha n half of t he ite ms are 
missi n g, t he ra w s c ore of t he d o mai n will be re g ar de d as missi n g. A n d t h e n, t he ra w sc ore of 
eac h d o m ai n will be tra nsf or me d i nt o a s c ore i n t h e 0 -1 0 0 scal e. Eac h d o mai n will be a nal yze d 
base d o n t he tra nsf or me d ra w sc ore.  
T he tra nsf or mi n g r ul es are s h o w n i n t he fi g ure b el o w: 
D o mai n  
Ra w sc ore tra nsf or mi n g r ule 
Restricti ve R ole F u ncti o n  
( Ra w sc ore - 7) * 1 0 0/ 3 5  
Pre ve nti ve R ole F u ncti o n  
( Ra w sc ore - 4) * 1 0 0/ 2 0  
E m oti o nal F u ncti o n  
( Ra w sc ore - 3) * 1 0 0/ 1 5  
T he tra nsf or me d ra w sc ore a n d c h a n ge fr o m b aseli ne f or eac h d o mai n will b e prese nt e d b y visit 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 3  of 3 6  
 
 
a n d d o mai n, wit h n,  me a n, S D , ma xi m u m, mi ni m u m, me dia n, a n d 9 5 % CI as des cri be d i n 
Secti o n 7. 1 . 
A listi n g of ori gi nal ite m sc ores a n d tr a nsf or me d sc ores f or eac h d o mai n fr o m t he M S Q o L 
q uesti o n naire will be  pr o vi de d.   
Mi grai ne Prefere n ce of Me dicati o n Q uesti o n nair e ( P o M)  
P o M is a 5 -ite m rati n g scale use d t o rec or d partici pa nt s’ perce pti o n of w het her t he st u d y dr u g 
t he y are t a ki n g is m ore b e neficial i n tr eati n g t heir pai n c o m pare d wit h pri or me dicati o n. T he 
statistical a nal ysis will be base d o n 3 cate g ori es , as s h o w n i n t he fi g ure bel o w: 
Ite m 
Cate g or y  
I feel m uc h better, a n d I prefer t his dr u g 
Prefere nce f or st u d y dr u g  
Sli g htl y better t ha n t he pri or me dicati o n  
Prefere nce f or st u d y dr u g  
Basicall y t he sa me as t he pri or me dicati o n  
N o prefere nce  
Sli g htl y w orse t ha n t he pri or me dicati o n  
Prefere nce f or pri or me dicati o n  
I feel m uc h w orse, a n d I prefer m y pri or me dicati o n Prefere nce f or pri or me dicati o n  
T he n u m ber a n d perce nta ge of partici pa nt s i n eac h cate g or y will be s u m marize d b y visit. T he 
calc ulati o n of perce nta g e will be base d o n partici pa nt s wit h P o M data b y  visit, a n d t he t w o -
si de d e xact Cl o p per -Pears o n 9 5 % CI  will be calc ulate d  as descri be d i n Secti o n 7. 1 . 
A listi n g of Prefere n ce of Me dicati o n ( P o M)   will be pr o vi de d.  
Satisfacti o n wit h Me dicati o n Q uesti o n naire ( S M)  
T he S M q uesti o n nair e is a 7 -ite m rati n g s cale use d t o rec or d w het her p arti ci pa nt s are s atisfie d 
wit h t he ir hea dac he  m e dicati o n . T he n u m ber a n d perce nta ge of partici p a nt s i n eac h cate g or y 
will be s u m marize d b y visit. T he calc ulati o n of p erce nt a ge will be b ase d o n partici pa nt s wit h 
S M data b y  visit , a n d t he t w o-si de d e xact Cl o p per -Pears o n 9 5 % CI  will be calc ulate d  as 
descri be d i n Secti o n 7. 1 . 
A lisri n g listi n g of Satisfacti o n wit h Me dicati o n ( S M) S ur ve y will be pr o vi de d . 
Mi grai ne Disa bilit y Assess me nt Q uesti o n naire ( MI D A S)  
T he 
MI D A S q uesti o n naire is a retr os pecti ve partici pa nt  self-re p ort scale c o nsisti n g of 5 
q uesti o ns, w hic h is use d t o meas ure disa bilit y relate d t o hea dac h e, s uc h as ti me l ost d ue t o 
hea dac he ca use d b y pai d w or k or sc h o ol, h o use w or k, a n d n o n -w or ki n g acti vities. T he val u e 
a n d c h a n ge fr o m bas eli ne i n t he t otal s c ore will be prese nt e d b y visit, wit h n,  mea n, S D , 
ma xi m u m, mi ni m u m, me dia n  a n d 9 5 % CI as d escri be d i n Secti o n 7. 1 .  
T he t otal sc ore is c alc ulat e d as t he s u m of ite m sc ores t o all 5 q uesti o ns.  
A listi n g of i n di vi d ual ite m sc ore, a n d t he calc ul ate d t otal sc ore will be pr o vi de d.  
Cli nical Gl o bal I m pr essi o n -c ha n ge ( C GI-c) scale  
T he C GI -c s cale is a 7 -ite m o bser ver-rate d s cale use d t o assess t he gl o b al i m pr o ve me nt i n 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 4  of 3 6  
 
 
partici pa nt s. T he n u m b er a n d perce nta ge of p artici pa nt s i n eac h cate g or y will be s u m marize d 
b y visit. T he calc ulati o n of perce nta ge will be bas e d o n partici pa nt s wit h C GI-c dat a b y  visit , 
a n d t he t w o-si de d e x act Cl o p per -Pears o n  9 5 % CI  will be calc ulate d.  
A listi n g of i n di vi d ual ite m res p o nses will be pr o vi de d.  
7. 5  S afet y A n al yses  
Safet y a nal yses d uri n g t he pre -treat me nt, treat me nt safet y a nal ysis peri o ds will be s u m marize d 
base d o n t h e S S . Safet y a nal yses f or f oll o w -u p safet y p eri o d  will be s u m marize d b ase d o n 
F U S S . 
7. 5. 1  Dr u g E x p os ure  
Dr u g a d mi nistrati o n dat a c ollect e d via C R F will be use d t o s u m mari ze dr u g e x p os ure as 
f oll o ws: 
● 
Ti me i n t he O P ( wee ks) = ( O P e n d dat e –  O P start date + 1)/ 7  
● 
Ti me i n t he L T T p eri o d ( wee ks) = ( L T T a nal ysis pe ri o d e n d date –  L T T a nal ysis 
peri o d  start date + 1)/ 7 
● 
Ti me o n  ri me ge pa nt e x p os ure ( wee ks) = ( st u d y dr u g e n d date –  st u d y dr u g start date 
+ 1)/ 7  
● 
C u m ulati ve a d mi nistere d ri me ge p a nt d ose  (ta blets) = s u m of d oses a d mi nistere d o n 
t he dr u g ma na ge m e nt pa ge of C R F . 
● 
A vera g e a d mi nistere d ri me ge pa nt d ose d uri n g t h e L T T  peri o d (ta bl ets per m o nt h ) = 
4 ( wee ks) *c u m ulati ve a d mi nistere d d ose (ta blets)  / Ti me  i n t he L T T peri o d ( wee ks) 
if ti me i n t he L T T peri o d ≥ 2 wee ks; =  c u m ulati ve a d mi nistere d d ose if ti me i n t he 
L T T peri o d  < 2 w ee ks .   
I n t he a b o ve dr u g e x p os ure s u m mar y, descri pti ve statistics of n, mea n, sta n d ar d de vi ati o n, 
me dia n, 2 5 t h a n d 7 5 t h perce ntiles, mi ni m u m a n d ma xi m u m will be prese nte d.  
● 
F or t he av era g e ri me ge p a nt e x p os ure d uri n g t he L T T  peri o d (ta blets  per m o nt h ), t he 
n u m ber a n d perce nt a ge of partici pa nts will be s u m marize d b y < 2 , ≥ 2  t o < 8 , ≥ 8  < 
1 4 , < 1 4 a n d ≥ 14  ta blets per m o nt h . 
● 
T he  n u m ber  a n d perce nta ge of partici pa nt s ta ki n g > 1 ta blet per da y (i.e., act ual d ose 
of “ ot her”) . It will be cal c ulate d base d o n t h e st u d y dr u g a d mi nistrati o n C R F .  
I n a d diti o n, ri me ge p a nt e x p os ure d uri n g t he L T T peri o d will be  s u m marize d b y t he a v era g e 
Ri me ge pa nt e x p os ure cat e g ories a n d t otal  f or eac h m o nt h (i.e., 4-wee k i nter val)  as defi ne d i n 
Ta ble 2 Ta bl e 2 . T he  ri me ge pa nt e x p os ure (t a blets) f or eac h m o nt h will be deter mi ne d as 
f oll o ws: 
● 
ri me ge pa nt e x p os ure  (ta blets) f or M o nt h X = s u m of d oses a d mi nistere d o n  t he dr u g 
ma na ge me nt pa ge of C R F  wit hi n t he M o nt h X wi n d o w, w here X = 1, 2, 3, 4, 5, 6, 7, 
8, 9, 1 0, 1 1, 1 2 . 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 5  of 3 6  
 
 
● 
ri me ge pa nt e x p os ure (ta blets) f or M o nt h 1 3 = s u m of d oses a d mi nistere d o n t he dr u g 
ma na ge me nt pa g e of C R F wit hi n t he M o nt h 1 3  wi n d o w  if e x p os ure ≤2 8 da ys; = s u m 
of d oses  a d mi nistere d  o n t he dr u g ma na g e me nt p a ge of C R F wit hi n t he M o nt h 1 3 
wi n d o w  * 2 8 /e x p os ure d a ys if e x p os ure > 2 8 d a ys.  
Partici pa nt ’s e x p os ure t o t he st u d y dr u g will be liste d i n detail. 
7. 5. 2  A d verse E v e nts  
T he A Es will be c o de d b y t he latest versi o n of M e d D R A. T he t o xicit y of A Es will be gra de d 
usi n g Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y f or A d verse E v e nts ( N CI C T C A E) v 5. 0.  
All A Es will be cate g ori ze d  acc or di n g t o t he safet y a nal ysis peri o d s (refer t o Secti o n 7. 2. 4 ), ie. 
pre -treat me nt safet y peri o d, treat me nt safet y peri o d , a n d f oll o w-u p  safet y p eri o d: 
● Pre -treat me nt A E s, ie, t h ose wit h i m p ute d A E o nset date s falli n g wit hi n  t he pre-
treat me nt safet y peri o d. 
● Treat me nt -e mer ge nt a d v erse e ve nt ( T E A E s), ie, t h ose wit h i m p ute d A E o nset dates 
falli n g wit hi n  t he tr eat me nt safet y peri o d . See Secti o n 7. 2. 1  f or A E o nset dat e 
i m p utati o n.  
● F oll o w -u p A E s, i.e., t h ose wit h i m p ute d A E o ns et date s falli n g wit hi n t h e f oll o w-u p 
safet y peri o d.  
Dr u g -relate d A Es are t he  A E s assesse d b y t he site i n vesti gat or as ha v i n g a relati o ns hi p t o t he 
i n vesti gati o nal pr o d uct  of  “ defi nitel y r elate d”, “ pr o ba bl y relate d ” , or “ p ossi bl y relate d”.   
A n  o verall s u m mar y of A Es will dis pla y  t he n u m ber a n d p erce nta ge of partici pa nt s re p orti n g 
t he f oll o wi n g A Es f or partici pa nts i n differe nt cat e g ories of a vera ge ri me ge pa nt e x p os ure  (< 2 , 
≥ 2  t o < 8 , ≥ 8  < 1 4 , < 1 4 a n d ≥ 14  ta bl ets per m o nt h) a n d o verall partici pa nts  f or tr eat me nt 
safet y a n d f oll o w -u p safet y a nal ysis peri o ds, res pecti vel y, as bel o w : 
•  
F or treat me nt safet y a nal ysis peri o d, t he f oll o wi n g will be s u m marize d usi n g S S :  
o  A n y T E A E,  a n y dr u g -rel ate d T E A E,  
o  A n y seri o us T EA E , a n y dr u g-relat e d seri o us T E A E,  
o  A n y T E A E wit h C T C A E gra de ≥ 3 , a n y dr u g-relat e d T E A E wit h C T C A E 
gra de ≥ 3,  
o  A n y T E A E lea di n g t o dr u g i nter r u pti o n; a n y dr u g-relate d T E A E lea di n g t o 
dr u g i nterr u pti o n,  
o  A n y T E A E lea di n g t o treat me nt disc o nti n uati o n, a n y  dr u g - relat e d T E A E 
lea di n g t o treat me nt disc o nti n uati o n,  
o  A n y T E A E lea di n g t o st u d y disc o nti n uati o n, a n y dr u g-relat e d T E A E lea di n g 
t o st u d y disc o nti n uati o n,  
o  A n y T E A E lea di n g t o deat h, a n y dr u g -relate d T E A E lea di n g t o deat h. 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 6  of 3 6  
 
 
•  F or f oll o w -u p s afet y a nal ysis peri o d, t he f oll o wi n g will be s u m marize d  usi n g F U S S :  
o  A n y A E ,  
o  A n y S A E ,  
o  A n y A E lea di n g t o deat h . 
F urt her, the n u m ber a n d perce nt a ge of partici pa nts wit h t he f oll o wi n g A Es will be ta b ulate d b y 
S O C a n d P T  f or partici pa nts i n differe nt cate g ories of a vera ge ri me ge p a nt e x p os ure < 2 , ≥ 2  t o 
< 8 , ≥ 8  < 1 4 , < 1 4 a n d ≥ 14  ta blets per m o nt h) a n d o verall p artici pa nts f or tr eat me nt safet y a n d 
f oll o w-u p safet y a nal ysis peri o ds, res pecti vel y, as bel o w : 
● F or treat me nt safet y a nal ysis peri o d, t he f oll o wi n g will be s u m marize d usi n g S S:  
o  T E A E s, 
o  Dr u g -relate d T E A Es,  
o  Seri o us T E A E s, 
o  Dr u g -relate d seri o us T E A Es. 
● F or f oll o w -u p safet y a n al ysis peri o d, t he f oll o wi n g cate g ories will be s u m marize d usi n g 
F U S S : 
o  A Es , 
o  Seri o us A Es.  
I n a d diti o n, the n u m ber  a n d perce nt a ge of p artici p a nts wit h t he f oll o wi n g A Es will be ta b ulate d 
b y S O C, P T, a n d ma xi m u m C T C A E gra de ( Gra d e 1, 2, 3, 4, 5, ≥ 3, ≥ 4) f or partici pa nts i n 
differe nt cat e g ories of a v era ge ri me ge p a nt e x p os ure (< 2 , ≥ 2  t o < 8 , ≥ 8  < 1 4 , < 1 4 a n d ≥ 14  
ta blets per m o nt h) a n d o verall partici pa nts f or treat me nt safet y a n d f oll o w -u p  safet y a nal ysis 
peri o ds, res pecti vel y, as bel o w :  
● F or treat me nt safet y a nal ysis peri o d, t he f oll o wi n g will be s u m marize d usi n g S S:  
o  T E A E s,  
o  Dr u g -relate d T E A Es.  
● F or f oll o w -u p safet y a n al ysis peri o d, t he f oll o wi n g cate g ories will be s u m marize d usi n g 
F U S S:  
o  A Es.  
F or t he a b o v e A E  ta bles t hat dis pla y C T C A E t o xicit y gra de, if t he s a me A E is re p ort e d b y t h e 
sa me partici pa nt re peat e dl y, t he A E wit h t he hi g hest N CI-C T C gra de ( Gra de 5 > Gra d e 4 > 
Gra de 3 > Gra d e 2 > Gra de 1 > Missi n g) will be prese nte d i n t he s u m mar y ta ble. T he 
partici pa nts  will be c o u nt e d o nce acc or di n g t o t h e hi g hest gra de u n der eac h u ni q ue P T ite m i n 
t he S O C.  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 7  of 3 6  
 
 
Partici pa nts re p orti n g t he f oll o wi n g  A E s will be liste d se parat el y usi n g S S : 
● A E s wit h C T C A E Gra de ≥3 , 
● A E s lea di n g t o treat me nt disc o nti n uati o n, 
● A E s lea di n g t o st u d y disc o nti n uati o n, 
● A E s lea di n g t o deat h,   
● A E s Lea di n g t o d r u g I nterr u pti o n. 
All A Es will be liste d b y  partici pa nt I D wit h a fl a g i n dicati n g eac h A E t o be a pre -tr eat me nt 
A E , a T E A E , or a f oll o w-u p A E .  
A  d eat h listi n g f or all t he scree n e d partici p a nts will be ge nerate d. 
7. 5. 3  Cli nical La b orat or y Tests  
T he cli nical la b orat or y e val uati o n res ults c ollecte d b y t he ce ntral la b orat or y will i ncl u de:  
( 1) Cli nical safet y la b orat or y tests 
He mat ol o g y: he m o gl o bi n, he mat ocrit, re d bl o o d cell c o u nt, w hite bl o o d cell c o u nts  wit h 
differe ntial c o u nt, a n d pl atelets.  
C he mistr y: s o di u m, p otassi u m, c hl ori de, bicar b o nate, calci u m; gl uc ose, H b A 1c, B U N ( urea), 
ser u m creati ni ne, uric aci d, lactate de h y dr o g e nase ( L D H), t otal pr otei n, al b u mi n, creati ne 
p h os p h o ki nase ( C P K) ( wit h fracti o nati o n test, if C K res ult is > 1. 5 × U L N),  esti mate d 
g l o mer ular filtrati o n rate (e G F R ) usi n g t h e esti m ate d m o dificati o n of d iet i n re nal d isease 
(M D R D ) f or m ula (cal c ulate d at ce ntr al la b), as partat e tra ns a mi nas e (A S T ), ala ni ne 
tra nsa mi nase (A L T ), Al k ali ne P h os p hatase ( A L P) a n d Bilir u bi n ( T otal, Direct, I n direct ). 
( 2) Bl o o d li pi d test: c h olester ol, l o w-de nsit y li p o pr otei n, hi g h -de nsit y li p o pr otei n, tri gl yceri de . 
( 3) Uri nal ysis: p H, s pecific gra vit y, ket o nes, nitrit e, ur o bili n o ge n, le u k oc yt e esterase, pr otei n, 
gl uc ose,  a n d occ ult bl o o d. Micr osc o pic e x a mi nati o n will be perf or me d if o cc ult bl o o d, pr otei n 
or w hite bl o o d cells are p ositi ve .  
( 4) F S H: f or W O C B P at scree ni n g visit t o deter mi ne W O C B P stat us. 
R es ults fr o m  ce ntral a n d l ocal la b orat or y  tests will be s u m marize d . F or l ocal la b orat or y 
para meters  wit h differe nt  u nits fr o m t he ce ntr al la b orat or y, t he res ults will be  c o n verte d . 
R es ults ca n n ot be c o n verte d will be i ncl u de d i n t he listi n g. 
F or t he  c o nti n u o us he m ato l o g y, c he mistr y, a n d bl o o d li pi d la b orat or y test para meters, o bser ve d 
val ues  a n d c ha n g es fr o m baseli ne will be s u m marize d at t he f oll o wi n g ti me p oi nts: baseli ne, 
eac h sc h e d ule d visit , earl y ter mi nati o n , a n d F oll o w -u p v isit usi n g t he S S .  
S u m maries will be perf or me d usi n g  ce ntral la b orat or y  res ults if b ot h ce ntral a n d l ocal 
la b orat ory para met ers  are c ollecte d at a visit . If t here are multi ple val ues c ollecte d at  t he s a me 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 8  of 3 6  
 
 
visit , r ule state d i n Secti o n 7. 2. 2  will be a p plie d.  
T he n u m ber a n d p erce nt a ge of p artici pa nt s wit h la b orat or y test a b n or malities acc or di n g t o 
C T C A E gra de ( Gra de 0; Gra de 1-2; Gra de 3 -4)  will be prese nte d d uri n g t h e treat me nt ( usi n g 
S S)  a n d f oll o w-u p ( usi n g F U S S) safet y a n al ysis peri o ds, res pecti vel y. T he hi g hest C T C A E 
gra de  d uri n g t h e a nal ysis peri o d will be  use d . A d diti o nall y, t he a b n or mal la b orat or y tests  i n at 
least 5 % of o verall partici pa nts  or C T C A E Gra de 3 -4  will be s u m marize d b y a vera ge 
ri me ge pa nt e x p os ure (< 2 , ≥ 2  t o < 8 , ≥ 8  < 1 4 , < 1 4 , ≥ 1 4  ta blets per m o nt h, a n d o verall ).  
T he  n u m ber a n d perce nta ge of partici p a nts wit h s hifts fr o m baseli nes i n C T C A E gra des  ( Gra de 
0, 1, 2, 3 , 4, 1-4)  t o t he tr eat me nt safet y peri o d  bas e d o n S S  (refer t o Secti o n 7. 2. 4 ) will als o be 
prese nte d , usi n g t he hi g h est C T C A E gra de.  
T he n u m ber a n d perce nt a ge of par tici pa nts wit h L F T ele vati o ns i n t he f oll o wi n g cate g ories will 
be prese nte d  d uri n g t he treat me nt  base d o n S S  safet y a nal ysis peri o d , f or partici pa nts i n 
differe nt cat e g ories of a v era ge ri me ge p a nt e x p os ure ( < 2 , ≥ 2  t o < 8 , ≥ 8  < 1 4 , < 1 4 a n d ≥ 14  
ta blets per m o nt h) a n d o v erall partici pa nts:  
● C u m ulati ve ele vati o ns  
A L T > 1 x, > 3 x, > 5 x, > 1 0 x, a n d > 2 0 x U L N  
A S T > 1 x, > 3 x, > 5 x, > 1 0 x, a n d > 2 0 x U L N  
A L T or A S T > 1 x, > 3 x, > 5 x, > 1 0 x, a n d > 2 0 x U L N  
T B L > 1 x a n d > 2 x U L N  
A L P > 1. 5 x U L N  
T hese are b ase d o n t he hi g hest rati o of v al ue t o U L N f or eac h l a b orat or y test. N ote t h at 
partici pa nts  ma y be i n > 1 cate g or y f or eac h la b orat or y test.  
● M ut uall y e xcl usi ve ele vati o ns  
A L T > U L N t o ≤ 3 x U L N, > 3 x U L N t o ≤ 5 x U L N, > 5 x U L N t o ≤ 1 0 x U L N, > 1 0 x  
U L N t o ≤ 2 0 x U L N, a n d > 2 0 x U L N  
A S T > U L N t o ≤ 3 x U L N, > 3 x U L N t o ≤ 5 x U L N, > 5 x U L N t o ≤ 1 0 x U L N, > 1 0 x  
U L N t o ≤ 2 0 x U L N, a n d > 2 0 x U L N  
T hese are b ase d o n t he hi g hest rati o of v al ue t o U L N f or eac h l a b orat or y test. N ote t h at 
partici pa nts  ma y be i n o nl y 1 cate g or y f or eac h la b orat or y test . 
● C o m p osite ele vati o ns  
A L T or A S T > 3 x U L N a n d T B L > 1. 5 x U L N. T his is base d o n t he hi g h est rati o of val ue 
t o U L N f or eac h la b orat or y test. 
A L T or A S T > 3 x U L N a n d T B L > 2 x U L N. T his is base d o n t he hi g hest rati o of val ue t o 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 2 9  of 3 6  
 
 
U L N f or eac h la b orat or y test.  
T he n u m ber a n d p erce nta ge of partici pa nts wit h s hifts i n L F T ele vati o ns fr o m baseli ne t o t h e 
treat me nt safet y peri o d usi n g S S  (refer t o Secti o n 7. 2. 4 ) will als o be prese nte d acc or di n g t o t he 
greatest ele v ati o n ; cate g ories f or A L T a n d A S T are ≤ U L N, > U L N t o ≤ 3 × U L N, > 3 × U L N 
t o ≤ 5 × U L N, > 5 × U L N t o ≤ 1 0 × U L N, > 1 0 × U L N t o ≤ 2 0 × U L N, a n d > 2 0 × U L N. 
All  la b orat or y data will be liste d usi n g S S . F or a gi ve n gra de d la b orat or y test, t he listi n g 
dis pla ys all test res ults o ver ti me f or partici pa nts wit h a C T C A E Gra de 3 t o 4 la b orat or y test 
a b n or malit y at a n y ti me p oi nt. F or a gi v e n pre g n a n c y test, t he listi n g als o dis pla ys all test res ults 
o ver ti me f or p artici pa nts wit h a p ositi ve pre g na n c y test res ult at a n y ti me p oi nt, defi ne d as a 
ser u m or uri ne pre g na n c y test wit h “ p ositi ve” c haracter val ue.  
T he scatter pl ot of e val uati o n of Dr u g -I n d u ce d Seri o us He p at ot o xicit y (e DI S H) d uri n g t he 
st u d y usi n g S S  will dis pla y t he ma xi m u m rati o of t otal bilir u bi n le vel di vi de d b y U L N o n t h e 
y -a xis vers us t he ma xi m u m rati o of A L T le vel di vi de d b y U L N o n t he x -a xis, w here t he 
ma xi ma are i n t he sa me st u d y peri o d b ut n ot necessaril y c o nc urre nt. B ot h a xes are o n t he l o g 1 0 
scale wit h mi ni ma of 0. 1. Rati os < 0. 1 x U L N are set t o 0. 1.  A h oriz o ntal refere nce li ne is 
place d at 2 x U L N, a n d a vertical refere n ce li ne is place d at 3 x U L N. T he l o wer left q ua dra nt is 
la bele d “ N or mal Ra n ge”, t he u p p er left q ua dra nt is la bele d “ H y per bilir u bi ne mia”, t he l o wer 
ri g ht q ua dra nt is l a bele d “ Te m ple’s C or ollar y”, a n d t he u p per ri g ht q ua dra nt is la bele d 
“ P ossi ble H y’s La w Ra n ge.” A f o ot n ote s pecifies t hat “ Rati os < 0. 1 x U L N are set t o 0. 1. ” a n d 
is dis pla ye d o nl y if  1 partici pa nt  has a rati o set t o 0. 1.  
7. 5. 4  Vital Si g ns a n d P h ysical Meas ure me nts  
F or eac h vital si g n para meter (s yst olic bl o o d press ure, diast olic bl o o d press ure, p ulse rate, 
res pirat or y rat e, te m perat ure) a n d p h ysical meas ure me nt para m eter  ( wei g ht, B MI), o bser v e d  
val ue s a n d c ha n g es fr o m baseli ne will be s u m marize d at t he f oll o wi n g ti me p oi nts: baseli ne, 
eac h sc he d ul e d visit , earl y ter mi nati o n , a n d F oll o w -u p v isit usi n g S S . See S ecti o n 7. 2 .2  f or 
ha n di n g m ulti ple val ues i n a n a nal ysis wi n d o w.  
T he n u m ber a n d perce nta ge of p art icipa nts wit h vital si g n  a b n or malities i n t he f oll o wi n g 
cate g ories will  be prese nt e d  d uri n g t he treat me nt  ( usi n g S S)  a n d f oll o w-u p ( usi n g F U S S) safet y 
a nal ysis peri o ds , res pecti vel y, f or partici pa nts i n differe nt cat e g ories of a vera ge ri me ge pa nt 
e x p os ure ( < 2 , ≥ 2  t o < 8 , ≥ 8  < 1 4 , < 1 4 a n d ≥ 14  t a blets per m o nt h) a n d o v erall partici pa nts:  
I n di vi d ual listi n g will be pr o vi de d usi n g S S . 
S yst olic B P ( m m H g)  
mi n. < 9 0  
 
S yst olic B P ( m m H g)  
ma x. > 1 4 0  
 
S yst olic B P ( m m H g) 
c ha n ge fr o m baseli ne  
ma x. decrease 
≥3 0  
ma x. i ncreas e 
≥3 0  
Diast olic B P ( m m H g)  
mi n. < 5 0  
 
Diast olic B P ( m m H g)  
ma x. > 9 0  
 
Diast olic B P ( m m H g) 
c ha n ge fr o m baseli ne 
ma x. decrease 
≥2 0  
ma x. i ncreas e 
≥2 0  
P ulse rate ( beats/ mi n ) 
mi n. < 4 0  
ma x. > 1 2 0  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3 0  of 3 6  
 
 
7. 5. 5  1 2 -lea d E C G 
F or eac h 1 2 -le a d E C G para meter ( heart rate, P R i nter val, Q R S d urati o n, Q T i nter val, a n d 
Q Tc F), t he o bser v e d val ues a n d c ha n g es fr o m baseli ne will be s u m marize d at t he f oll o wi n g 
ti me p oi nts: baseli ne, eac h sc he d ule d visit , earl y ter mi nati o n , a n d F oll o w-u p v isit usi n g S S . See 
Secti o n 7. 2. 2  f or ha n di n g m ulti ple val ues i n a n a nal ysis wi n d o w. 
T he n u m ber a n d perce nta ge of partici pa nts wit h E C G a b n or malities i n t he f oll o wi n g cate g ories  
will be pres e nte d d uri n g t he treat me nt safet y ( usi n g S S) a n d f oll o w -u p  ( usi n g F U S S) safet y 
a nal ysis peri o ds , res pecti vel y, f or partici pa nts i n differe nt cat e g ories of a vera ge ri me ge pa nt 
e x p os ure ( < 2 , ≥ 2  t o < 8 , ≥ 8  < 1 4 , < 1 4 a n d ≥ 14  t a blets per m o nt h) a n d o v erall partici pa nts: 
● Q Tc F ( msec): ≤4 5 0, 4 5 0 - ≤4 8 0, 4 8 0 - ≤5 0 0 , > 5 0 0 
● Q Tc F i ncrease fr o m b aseli ne ( msec): ≤3 0, 3 0  - ≤6 0 , > 6 0. 
I n di vi d ual listi n g will be pr o vi de d usi n g S S . 
7. 6   C O VI D -1 9 -rel ate d Visit I m p act 
A  listi n g of e nr olle d partici pa nt s wit h visits i m pacte d b y C O VI D -1 9 will be pr o vi de d. T h e 
listi n g will c o ntai n t he f oll o wi n g i nf or mati o n: “ W hat was t he i m pact?”, “ H o w was t he i m pact 
relate d t o C O VI D-1 9 ?”, a n d “ Di d t he p artici pa nt  wit h dra w fr o m t he st u d y d u e t o C O VI D -1 9?”.  
8  
A P P E N DI X  
8. 1  T he Deri v ati o n of Mi gr ai ne D a y  
Mi grai ne Da y D eri vati o n  
e Diar y l o gs wit h all e ve ni n g q uesti o ns a n d f oll o w -u p q uesti o ns bei n g e m pt y will be delete d.  
A mi grai ne da y is defi n e d as a n e Diar y da y wit h eit her (I) or (II):  
I. Q ualifie d mi grai ne h ea dac he b ase d o n all t he f oll o wi n g criteria (a a n d b):  
a. Lasti n g f or ≥ 3 0 mi n utes:  
i. 
Hea dac he d urati o n  
= ( 1) H ea dac he e n d ti m e # –  h ea d ac he start ti me #, w here h ea dac he start a n d e n d 
dates ( wit h “ E N D E D ” t o t he q uesti o n a b o ut hea dac he stat us) are t he sa me, a n d 
e Diar y e ntr y date is o n t h e sa me date;  
= ( 2) H ea dac he e n d ti m e # –  h ea d ac he start ti me #, w here h ea dac he start a n d e n d 
dates ( wit h “ E N D E D ” t o t he q uesti o n a b o ut h ea dac h e stat us) are t h e sa me, b ut 
e Diar y e ntr y date is later t ha n t he hea d ac he start d ate;  
= ( 3) Hea d ac he e n d ti me # –  0 o’cl oc k of t he hea dac he e n d date, w here h ea dac he 
e n d date ( wit h “ E N D E D ” t o t he q uesti o n a b o ut hea dac he stat us) is later t ha n t he 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3 1  of 3 6  
 
 
hea dac he start date, a n d e Diar y e ntr y d ate is later t ha n t he h ea dac he st art date b ut 
c o ul d be eit her e q ual t o or later t ha n t he h ea dac he e n d date . 
= ( 4) Hea d ac he e n d ti me # –  0  o’cl oc k of t he hea dac he e n d date, w here h ea dac he 
start date is missi n g, hea dac h e e n d date ( wit h “ E N D E D” t o t he q uesti o n a b o ut 
hea dac he st at us) is a vaila ble a n d e Di ar y e ntr y d ate is eit her e q u al t o or later t ha n 
t he hea dac he e n d date, a n d f oll o w-u p l o g is n ot a vaila ble . 
ii. 
Hea dac he -t o-e ntr y d urati o n  
= ( 1) e Diar y e ntr y ti me # –  hea d ac h e start ti me #, w here hea d ac h e start a n d e Diar y 
e ntr y dates are t he sa m e, a n d h ea d ac he e n d ti me # is missi n g ( n ot a ns were d or 
“ S TI L L C O N TI N UI N G” t o t he q uesti o n a b o ut hea dac h e stat us);  
= ( 2) e Diar y e ntr y ti me # –  0 o’cl oc k of t he e ntr y date, w here e Diar y e ntr y date is 
later t ha n t he hea dac he st art date, a n d h ea d ac he e n d ti me # is missi n g ( n ot a ns were d 
or “ S TI L L C O N TI N UI N G” t o t he q uesti o n a b o ut hea dac he stat us).  
iii. 
Hea dac he -t o-F U d urati o n  
= f oll o w -u p l o g hea dac he e n d ti me @ or f oll o w -u p l o g e ntr y ti me @ –  hea dac he start 
ti me #, w here f oll o w-u p hea dac he l o g is a vaila ble wit h a hea dac he e n d ti me or a 
f oll o w-u p l o g e ntr y ti me if hea dac he e n d ti me is missi n g.  
i v. 
F or partici p a nts w h o ha v e a hea d ac he o cc urre nce lasti n g f or > 1 cale n dar d a y s uc h 
t hat ≥1 e ve ni n g l o gs are rec or de d o n c o nsec uti ve e Diar y e ntr y da ys wit h t he sa me 
occ urre nce start ti me a n d hea dac he e n d ti me bei n g 
missi n g (i.e. “ S TI L L 
C O N TI N UI N G” st at us) f or ear lier d a ys a n d n o n-missi n g (i.e. “ E N D E D” stat us) f or 
t he last da y, d u plicate t he e ve ni n g l o g t hat is(e ntere d after hea d ac h e start date) a n d 
(t he l o g pri or t o t his l o g d oes n ot ha ve a s a me hea dac h e start date). Calc ulate t he 
f oll o wi n g d urati o n f or t h e d u plicate d e v e ni n g l o g, 
Hea dac he -t o-mi d ni g ht d urati o n  
= mi d ni g ht of t he da y - h ea dac he start ti me #.  
T hat is, f or e xa m ples b el o w, partici pa nt 2 l o g 2 a n d partici pa nt 3 l o g 2 will eac h b e 
s plit i nt o 2 l o gs:  
f or partici pa nt 2, l o g 2 will be s plit i nt o a n a d de d l o g wit h hea dac he starti n g fr o m 
1 9 A U G 2 0 2 2: 2 1: 1 0: 0 0 t o mi d ni g ht (i.e., d urati o n i n i v) a n d a n ori gi nal l o g wit h 
hea dac he starti n g fr o m 0’cl oc k t o e ntr y ti me of 2 0 A U G 2 0 2 2: 1 9: 5 4: 5 1 [i.e. d urati o n 
i n ii ( 2)];  
f or partici pa nt 3, l o g 2 will be s plit i nt o a n a d de d l o g wit h hea dac he starti n g fr o m 
1 7 M A R 2 0 2 3: 1 7: 3 0: 0 0 t o mi d ni g ht (i.e., d urati o n i n i v) a n d a n ori gi nal l o g wit h 
hea dac he starti n g fr o m 0’cl oc k t o 1 8 M A R 2 0 2 3: 2 1: 0 0: 0 0 [i.e. d urati o n i n i ( 3)].  
Partici
pa nt 
I D 
L o g  e Diar y E ntr y Ti me  
Hea dac he 
( Y E S/ N O
) 
Hea dac he Start Ti me  Hea dac he E n d Ti me  Hea dac he Stat us  
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3 2  of 3 6  
 
 
1  
1  
2 3 S E P 2 0 2 2: 2 1: 5 4: 2 2  Y E S  
2 3 S E P 2 0 2 2: 1 8: 3 3: 0 0    
S TI L L 
C O N TI N UI N G  
1  
2  
2 4 S E P 2 0 2 2: 2 2: 3 8: 1 7  Y E S  
2 3 S E P 2 0 2 2: 1 8: 3 3: 0 0    
S TI L L 
C O N TI N UI N G  
1  
3  
2 5 S E P 2 0 2 2: 2 2: 5 7: 3 0  Y E S  
2 3 S E P 2 0 2 2: 1 8: 3 3: 0 0  2 5 S E P 2 0 2 2: 0 8: 2 2: 0 0  E N D E D  
2  
1  
1 9 A U G 2 0 2 2: 1 9: 1 9: 2 9  N o  
  
  
  
2  
2  
2 0 A U G 2 0 2 2: 1 9: 5 4: 5
1  
Y E S  
1 9 A U G 2 0 2 2: 2 1: 1 0: 0
0  
  
S TI L L 
C O N TI N UI N G  
2  
3  
2 1 A U G 2 0 2 2: 1 8: 1 6: 4 0  Y E S  
1 9 A U G 2 0 2 2: 2 1: 1 0: 0 0  2 0 A U G 2 0 2 2: 1 5: 1 5: 0
0  
E N D E D  
3  
1  
1 6 M A R 2 0 2 3: 1 9: 4 7: 4
5  
Y E S  
1 6 M A R 2 0 2 3: 1 1: 0 0: 0
0  
1 6 M A R 2 0 2 3: 1 9: 4 8:
0 0  
E N D E D  
3  
2  
1 8 M A R 2 0 2 3: 2 1: 2 8: 5
7  
Y E S  
1 7 M A R 2 0 2 3: 1 7: 3 0: 0
0  
1 8 M A R 2 0 2 3: 2 1: 0 0:
0 0  
E N D E D  
v.  
A l o g is c o nsi dere d as l asti n g f or ≥ 3 0 mi n utes if t he res p o nse t o q uesti o n a b o ut 
hea dac he lasti n g ≥ 3 0 mi n utes is “ Y E S”, or a n y of t he d urati o ns cal c ulate d i n i, ii, 
iii is ≥ 3 0 mi n utes; a n d a d u plicate d e ve ni n g l o g is c o nsi dere d as lasti n g f or ≥ 3 0 
mi n utes if d urati o n calc ulate d i n i v is ≥ 3 0 mi n utes.  
vi.  
Defi ne a n e Di ar y refere n ce date t o be t he e Diar y e ntr y date f or sce nari os i ( 1), ii 
( 1), ii ( 2), a n d h ea d ac he start date f or s ce nari os i ( 2), iii, i v, a n d h ea dac he e n d date 
f or sce n ari o i ( 3) a n d i ( 4) . A mi grai ne da y will be i de ntifie d base d o n t h e e Diar y 
refere nce date. 
b.  Meeti n g at least o ne of t h e f oll o wi n g criteria (i or ii):  
i. 
≥ 2 of t he f oll o wi n g pai n feat ur es base d o n “ yes” res p o nse t o q uesti o ns wit h t he sa me 
e Diar y refere n ce dat e/ti me:  
▪ 
U nilateral l ocati o n #,  
▪ 
P ulsati n g q ualit y (t hr o b bi n g) #,  
▪ 
M o derate or s e vere pai n i nte nsit y #  
▪ 
A g gra vati o n b y or ca usi n g a v oi da nce of r o uti ne p h ysical acti vit y (e. g. wal ki n g 
or cli m bi n g stairs) #  
ii. 
≥ 1 of t he f oll o wi n g ass ociate d s y m pt o ms base d o n “ yes” res p o nse t o q uesti o ns wit h 
t he sa me e Diar y refere nce date/ti me: 
▪ 
Na usea #  
▪ 
V o miti n g #  
▪ 
B ot h p h ot o p h o bia # a n d p h o n o p h o bia #  
II. Ta ki n g tri pta n, er g ota mi ne or st u d y me dicati o n: “ Yes” res p o nse t o t he q uesti o n a b o ut ta ki n g 
tri pta n t o treat hea dac he or d uri n g a ura # @, q uesti o n a b o ut ta ki n g er g ota mi ne t o treat hea dac he 
or d uri n g a ura # @, or q uesti o n a b o ut ta ki n g st u d y me dicati o n t o treat hea d ac he or d uri n g a ura 
# @ &  i n t he L T T a nal ysis peri o d. 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3 3  of 3 6  
 
 
N ote t hat data mar ke d wit h “ #” are i de ntifie d fr o m t he e ve ni n g hea dac he l o g; data mar ke d wit h 
“ @” are i de ntifie d fr o m t he f oll o w -u p h ea d ac he l o g ; data mar k e d wit h “ &” are i d e ntifie d fr o m 
dr u g a d mi nistrati o n i nf or mati o n c ollecte d via C R F. 
III. After a mi grai ne d a y is deri ve d base d o n ste ps I a n d II f or eac h l o g, t he l o gs wit h d u plicate d 
e Diar y refere n ce d ate will be de d u pe d b y kee pi n g t he ori gi nal l o g if b ot h ori gi nal l o g a n d a d d e d 
l o g are o n t he sa me refere nce dat e, f oll o w e d b y kee pi n g t he o ne wit h mi grai ne d a y 
i de ntificati o n = Y E S, ne xt  f oll o we d b y kee pi n g t he m ost se vere mi grai n e, a n d t he n f oll o we d b y 
kee pi n g t he l o g wit h t he latest hea dac he e n d date. 
8. 2  T he M a p pi n g R ule f or P D C ate g o ries  
D uri n g t he B H V 3 0 0 0 -3 1 8 ( C 4 9 5 1 0 1 8) st u d y, t he pr ot oc ol de viati o n cate g orizati o n f or m a n d 
rec or d f or m w ere u p dat e d d ue t o c ha n ges i n t he Ti ger me d S O P a n d as per t h e Pfizer 
re q uire me nts. T he u p date d d oc u me nt beca me effecti ve i n t he s yste m o n 2 7 J ul y 2 0 2 3. T he ne w 
cate g oriz ati o n f or m has ma de s o me c ha n ges t o t he P D cate g orizati o ns c o m pare d t o t he ol d 
versi o n, w hic h i ncl u des assi g ni n g P Ds i nt o m ore refi ne d s u b -cate g ories, a n d m o dif yi n g t he P D 
se verit y criteri a. F or e x a m ple, bef ore t he u p dat e, t he cate g ori es were la bele d A, B, C … J, wit h 
c orres p o n di n g s u b -cate g ories were A 1, A 2, A 3, A 4, B 1, B 2, a n d s o o n; after t he u p dat e, t he 
cate g ories w ere c ha n g e d t o 1), 2), 3)... 9), a n d t here are se v eral s u b -cat e g ories u n der eac h 
cate g or y; t he se verit y le vels w o ul d be Maj or/ M i n or bef ore t he u p date, a n d were u p date d t o 
I m p ort a nt/ N o n-i m p orta nt. Si nce t he P D data i n t he ol d a n d ne w versi o ns of t he cate g ori zati o n 
f or ms ma y n ot c orres p o n d t o eac h ot h er or ca n n ot be dir ectl y c o n vert e d bet wee n eac h ot her, 
P Ds are prese nte d i n t w o dif fere nt fas hi o ns i n t he c urre nt P D l o g. I n or der t o prese nt a 
c o nsiste nt P D cate g oriz ati o n i n t he fi nal C S R, t he f oll o wi n g d ecisi o n was m a de u p o n 
disc ussi o n wit hi n t he st u d y tea m fr o m Pfizer a n d Ti ger me d:  
A cc or di n g t o t he re g ulat or y re q uire me nts a n d t he Pfizer a n d Ti ger me d S O Ps, a nal ysis o n 
I m p ort a nt P Ds w o ul d be prese nte d i n t he C S R b o d y. Si nce t he defi niti o ns a n d criteria f or 
I m p ort a nt P D i n t he ol d versi o n are g e nerall y c o nsiste nt wit h t h ose f or Maj or P D i n t he ne w 
versi o n, wit h t he o nl y differe n ce l yi n g i n t hat t he s a me P D w o ul d b e cate g orize d i nt o differe nt 
cate g ories i n t he t w o v ersi o ns, it is p ossi ble t o c o n vert a Maj or P D i nt o a n I m p orta nt P D 
f oll o wi n g c o nsiste nt r ules, as well as c o n verti n g a C O VI D-1 9 -rel ate d Mi n or P Ds i nt o N o n-
i m p orta nt P Ds. 
T he rec o m me n de d r ules f or ma p pi n g t he ol d cate g orizati o n of 
M aj or P Ds t o t he n e w 
cate g oriz ati o n of I m p orta nt P Ds are as f oll o ws:  
•  T he ori gi nal A 2 “ S u bject has si g n e d I C F, b ut di d n ot si g n t he u p d ate d I C F a n d 
c o nti n ue d i n t he trial” c orres p o n ds t o 1 1) -1 0 “I C F si g ne d b y t he s u bject or s u bject’s 
le gal re pres e ntati ve is a s u perse de d or o ut date d versi o n (t he P D will be re gar de d as 
I m p orta nt if t he u p date d I C F c o ntai ns u p date d or i m p orta nt i nf or mati o n o n ris k -relate d 
la n g ua ge)”. 
•  T he ori gi nal A 4 “I nf or m e d c o nse nt pr ocess or I C F c o m pleti o n, ma na ge m e nt or ot her 
as pects di d n ot meet re q uire me nts” c orres p o n ds t o 1 1) -7 “ U p date d I C F was n ot si g ne d 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3 4  of 3 6  
 
 
at t he first visit after E C a p pr o val (t he P D will be re gar de d as I m p orta nt if t he u p date d 
I C F c o ntai ns u p date d or i m p orta nt i nf or mati o n o n ris k-relate d l a n g ua ge)”. 
•  T he ori gi nal B 2 “ S u bject met e xcl usi o n criteria, b ut e ntere d t h e st u d y” c orres p o n ds t o 
1) -2 “ S u bject met e x cl usi o n criteria, b ut e ntere d t he st u d y”.  
•  T he ori gi nal C 2 “ St u d y dr u g d ose err or (refer t o pr ot oc ol 7. 2. 2 a n d 7. 2. 3”) c orres p o n ds 
t o 2) -2 “ Err or i n st u d y dr u g d ose or met h o d of a d mi nistrati o n, etc. (refer t o pr ot oc ol 
7. 2. 2 a n d 7. 2. 3)”.  
•  T he ori gi nal C 4 “ St u d y dr u g was n ot st ore d or tra ns p orte d per pr ot oc ol, a n d was 
a d mi nistere d t o t he s u bject bef ore it was assesse d as usa ble b y t he s p o ns or” c orres p o n ds 
t o 2) -4 “ St u d y dr u g st ora ge iss ues (e. g., if s u bject was dis pe nse d a n d use d st u d y dr u g  
wit h te m perat ure e x c ursi o ns t hat has bee n dee me d n ot usa ble or has n ot be c o nfir me d 
as w het her or n ot usa ble, it w o ul d be re gar de d as a n I m p orta nt P D. If s u bject was 
dis pe nse d st u d y dr u g wit h te m perat ure e xc ursi o ns b ut di d n ot use it, or us e d it after it 
was c o nfir me d t o be f urt her usa ble, it w o ul d be re gar de d as a N o n -i m p orta nt P D”. 
•  T he ori gi nal D 1 “ S u bject use d pr ot oc ol -pr o hi bite d me dicati o ns or t hera pies d uri n g t he 
trial” c orres p o n ds t o 3) -1 “ S u bject use d pr ot oc ol -pr o hi bite d me dicati o ns or t hera pies”.  
•  T he ori gi nal E 1 “ Pre g na nc y test (if a p plica bl e) 
missi n g” c orres p o n ds t o 4) -3 
“ Pre g na nc y t est missi n g”.  
•  T he ori gi nal E 2 “ S u bject e ntere d st u d y des pite missi n g la b orat or y assess me nts or 
a u xiliar y e xa mi nati o ns, etc., c o ncer ni n g t he eli gi bilit y criteria” c orres p o n ds t o 6) -3 
“ St u d y pr oce d ure or e x a mi nati o n missi n g or i nc o m plete (f or i n dicat ors c o ncer ni n g t he 
assess me nt of eli gi bilit y criteria or pri mar y e n d p oi nt, if t he pr oce d ure/e xa mi nati o n has 
ha d a n i m p orta nt i m pact o n st u d y res ults, e. g., w here t he pr oce d ure/e xa mi nati o n was 
missi n g f or m ore t ha n 1 2 c o nsec uti ve wee ks, it w o ul d be re gar de d as I m p orta nt)”.  
•  T he ori gi nal E 5 “e Diar y or B Y O D n ot c o m plete d per pr ot oc ol (t o b e assess e d as Maj or 
i n case of e Diar y missi n g f or 6 or m ore ti mes a m o nt h)” c orres p o n ds t o 6) -2. T he 
ori gi nal E 6 c orres p o n ds t o 6) -5 if wit h t he ke y w or d s “c o ntr ace pti o n” or “ pre g na nc y ” 
i n t he P D d escri pti o n, or t o 6) -2 “st u d y pr oce d ure or e xa mi nati o n (e Diar y c o m pleti o n, 
E C G, p h ysical e xa mi nati o n, q uesti o n naire, rati n g scale, et c.) n ot d o ne p er pr ot oc ol” if 
wit h o ut t he a b o ve ke y w or ds. T he ori gi nal F 2 “ Vis it missi n g” c orres p o n ds t o 5) -2 
“ Visit missi n g (t o be re g ar de d as I m p orta nt if t he missi n g visit has ha d a n i m p orta nt 
i m pact o n st u d y res ults, e. g., lea di n g t o safet y data missi n g f or m ore t ha n 1 2 wee ks or 
wit h dra wal fr o m visit)”.  
•  T he ori gi nal J 1 “ N ot fitti n g i nt o a n y of t he a b o ve cate g ories” c orres p o n ds t o 1 0) -1 “ N o 
sta n dar d s u b-cate g ories ”.  
T he rec o m me n de d r ules f or ma p pi n g t he of cate g orizati o n of Mi n or P Ds d ue  t o C O VI D-1 9 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3 5  of 3 6  
 
 
t o t he ne w cat e g orizati o n of N o n-I m p orta nt P Ds d ue t o C O VI D-1 9 are as f oll o ws:  
•  T he ori gi nal F 1 “ Visit o ut of all o wa bl e wi n d o w” c orres p o n ds t o 5) -1 “ Visit n ot 
perf or me d p er pr ot o c ol ( visit o ut of wi n d o w)”.  
•  T he ori gi nal F 2 “ Visit missi n g” c orres p o n ds t o 5) -2 “ Visit missi n g (t o be re gar de d as 
I m p ort a nt if t h e missi n g visit has ha d a n i m p orta nt i m pact o n st u d y res ults, e. g., lea di n g 
t o safet y data missi n g f or m ore t ha n 1 2 wee ks or wit h dra wal fr o m visit)”. 
•  T he ori gi nal 
E -3 “ Ot her la b orat or y tests, p h ysical e xa mi nati o n, vital si g ns, 
q uesti o n naire, or ot her pr ot oc ol -s pecifi e d pr oce d ures missi n g” c orres p o n ds t o 6) -3 
“ St u d y pr oce d ure or e x a mi nati o n missi n g or i nc o m plete (f or i n dicat ors c o ncer ni n g t he 
assess me nt  of eli gi bilit y criteria or pri mar y e n d p oi nt, if t he pr oce d ure/e xa mi nati o n has 
ha d a n i m p orta nt i m pact o n st u d y res ults, e. g., w here t he pr oce d ure/e xa mi nati o n was 
missi n g f or m ore t ha n 1 2 c o nsec uti ve wee ks, it w o ul d be re g ar de d as I m p orta nt)” if 
wit h t he k e y w or d “ vital si g ns” i n t he P D descri pti o n, or t o 4) -4 “ La b test n ot d o ne (f or 
i n dicat ors c o ncer ni n g t he assess me nt of eli gi bilit y criteria or pri mar y e n d p oi nt, if t he 
test has ha d a n i m p orta nt i m pact o n st u d y res ults, e. g., w here t he test was missi n g f or 
m ore t ha n 1 2 c o ns ec uti v e wee ks, it w o ul d b e re g ar de d as I m p orta nt) ” if wit h o ut t he 
a b o ve ke y w or d.  
•  T he ori gi nal E -4 “ La b test or ot her pr oce d ure o ut of pr ot oc ol -s pecifie d wi n d o w” 
c orres p o n ds t o 6) -2 “st u d y pr oce d ure or e x a mi nati o n (e Diar y c o m pl eti o n, E C G, 
p h ysical e xa mi nati o n, q u esti o n naire, rati n g scale, etc.) n ot d o ne per pr ot oc ol”.  
•  T he ori gi nal E -6 “ La b orat or y test, c o ntrace pti ve meas ure or ot her pr oce d ure n ot d o ne 
per pr ot oc ol or L a b Ma n ual ” c orres p o n ds t o 4) -4 “ La b test n ot d o ne (f or i n dicat ors 
c o ncer ni n g t he assess me nt of eli gi bilit y criteria or pri mar y e n d p oi nt, if t he test has  ha d 
a n i m p orta nt i m pact o n st u d y res ults, e. g., w here t he test was missi n g f or m ore t ha n 1 2 
c o nsec uti ve 
wee ks, it 
w o ul d be re gar de d as I m p orta nt) ” if 
wit h t he ke y w or d 
“ bicar b o nate” i n t he P D descri pti o n; or t o 6) -2 “st u d y pr oce d ure or e xa mi nati o n 
(e Diar y c o m pleti o n, E C G, p h ysical e xa mi nati o n, q uesti o n naire, rati n g scale, etc.) n ot 
d o ne per pr ot o c ol” if wit h t he ke y w or d “li ver f u ncti o n”; or t o 4) -7 “ L a b orat or y test 
pr ocess di d n ot m eet pres cri be d c o n diti o ns (i ncl u di n g s u bject’s state at bl o o d c ollecti o n 
an d s peci me n h a n dli n g, etc.) b ut s peci me n was a nal yze d ” if wit h t h e ke y w or d 
“tra ns p ort”; or t o 5) -1 “ Visit n ot perf or me d per pr ot oc ol ( visit o ut of wi n d o w)” if 
wit h o ut t he a b o ve ke y w or ds.  
O nce ma p pe d i nt o t he c orres p o n di n g ne w cate g ories, all Maj or P Ds will be s u m marize d as 
I m p ort a nt P Ds, a n d all ( Mi n or) P Ds d ue t o C O VI D-1 9 will be s u m marize d as ( N o n -i m p orta nt) 
P Ds d ue t o C O VI D -1 9 i n t he C S R. T he a b o ve is here b y s pecifie d.  
 
9  
R E F E R E N C E S  
G ui deli nes o n t he Pla n ni n g a n d Re p orti n g of Dr u g Cli nical Data Ma n a ge me nt a n d Statistical 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)


Fi nal  A nal ysis Pla n  
Pr ot oc ol N o.: B H V 3 0 0 0 -3 1 8/ C 4 9 5 1 0 1 8  
A pril 0 7 , 2 0 2 3 
C o nfi de ntial  
Pa ge 3 6  of 3 6  
 
 
A nal ysis ( Attac h me nt of 2 0 1 6 N o. 1 1 3 A n n o u nce me nt)  
G ui deli ne o n Bi ostatistics i n Cli nical Trials ( Attac h me nt of 2 0 1 6 N o. 9 3 A n n o u nce me nt) 
 
0 9 0 1 7 7 e 1 a 0 6 0 3 9 e e\ A p pr o v e d\ A p pr o v e d O n: 1 0- S e p- 2 0 2 4 0 1: 4 0 ( G M T)