Conditions: Migraine
Keywords: Migraine Prevention Prophylaxis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1590
Healthy volunteers: no

Brief summary:
The purpose of this is study is to compare the efficacy of BHV-3000 (rimegepant) to placebo as a preventive treatment for migraine, as measured by the reduction in the number of migraine days per month.

Detailed description:

Arms:
arm 1: DBT Phase (Weeks 1 through 12): Participants received a single oral dose of rimegepant 75 mg tablet every other day (EOD) for 12 weeks.

OLE Phase (Weeks 13 through 64): Participants who continued to meet study entry criteria and had acceptable laboratory test results per protocol, entered the OLE phase and received a single oral dose of rimegepant 75 mg tablet EOD for 52 weeks. If participants had a migraine on a day that they were not scheduled to dose with rimegepant, they could take one tablet of rimegepant 75 mg on that calendar day to treat a migraine (as needed \[PRN\] dosing).

After completing the OLE phase, participants had follow-up safety visits 2 and 8 weeks after the End-of-Treatment (EOT) visit. Participants who did not complete the DBT phase and/or did not enter or complete the OLE phase were to complete the EOT visit, the 2-week follow-up safety visit, and the 8-week follow-up safety visit after their early discontinuation. arm 2: DBT Phase (Weeks 1 through 12): Participants received a single oral dose of placebo matching to rimegepant tablet EOD for 12 weeks.

OLE Phase (Weeks 13 through 64): Participants who continued to meet study entry criteria and had acceptable laboratory test results per protocol, entered the OLE phase and received a single oral dose of rimegepant 75 mg tablet EOD for 52 weeks. If participants had a migraine on a day that they were not scheduled to dose with rimegepant, they could take one tablet of rimegepant 75 mg on that calendar day to treat a migraine (PRN dosing).

After completing the OLE phase, participants had follow-up safety visits 2 and 8 weeks after the End-of-Treatment (EOT) visit. Participants who did not complete the DBT phase and/or did not enter or complete the OLE phase were to complete the EOT visit, the 2-week follow-up safety visit, and the 8-week follow-up safety visit after their early discontinuation.

Interventions: intervention 1: Rimegepant intervention 2: Placebo
Intervention descriptions: intervention 1: Rimegepant 75 mg tablet EOD intervention 2: Placebo tablet to match rimegepant tablet EOD

Protocol document:
SAP_002.pdf: 
 
Biohaven Pharmaceuticals 
 
Protocol BHV3000-305 
 
A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to 
Evaluate the Efficacy and Safety of Rimegepant in Migraine Prevention 
Statistical Analysis Plan 
 
 
Version 10.0
Date: 16-Nov-2021  


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Statistical Analysis Plan for Protocol BHV3000-305 
Page 2 of 102
SIGNATURE PAGE 
Protocol Title: 
BHV3000-305: A Phase 2/3, Randomized, Double-
blind, Placebo-controlled Study to Evaluate the 
Efficacy and Safety of Rimegepant in Migraine 
Prevention
Sponsor: 
Biohaven Pharmaceuticals, Inc. 
Protocol Number: 
BHV3000-305 
Document Version/Date: 
Version 10.0/16-Nov-2021
Author: 
  
, 
 Biohaven 
Pharmaceuticals 
Signature:____________________________________ 
Date:________________________________________ 
Sponsor Approval 
By signing this document, I acknowledge that I have read the document and approve of the 
planned statistical analyses described herein.  I agree that the planned statistical analyses are 
appropriate for this study, are in accordance with the study objectives, and are consistent with 
the statistical methodology described in the protocol, clinical development plan, and all 
applicable regulatory guidelines. 
I have discussed any questions I have regarding the contents of this document with the 
biostatistical author.
I also understand that any subsequent changes to the planned statistical analyses, as described 
herein, may have a regulatory impact and/or result in timeline adjustments.  All changes to the 
planned analyses will be described in the clinical study report (CSR). 
Sponsor Signatories:
 
, 
 
 
Biohaven Pharmaceuticals
Signature:____________________________________ 
Date:________________________________________ 
, 
 
 Biohaven 
Pharmaceuticals  
Signature:____________________________________ 
Date:________________________________________ 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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TABLE OF CONTENTS 
SIGNATURE PAGE........................................................................................................ 2
LIST OF TABLES ........................................................................................................... 6
LIST OF FIGURES ......................................................................................................... 6
ABBREVIATIONS.......................................................................................................... 7
REVISION HISTORY .................................................................................................... 9
1 
INTRODUCTION AND OBJECTIVES OF ANALYSIS ................................... 18
1.1 
Introduction ........................................................................................................ 18 
1.2 
Study Objectives................................................................................................. 18
1.2.1 
Primary Objectives ...................................................................................... 18
1.2.2 
Secondary Objectives................................................................................... 18
1.2.3 
Exploratory Objectives ................................................................................ 19 
2 
STUDY DESIGN .................................................................................................... 20 
2.1 
Synopsis of Study Design ................................................................................... 20 
2.2 
Randomization Methodology ............................................................................ 21 
2.3 
Study Estimands ................................................................................................ 23
2.3.1 
Primary Objective Estimands ..................................................................... 23
2.3.2 
Secondary Objective Estimands ................................................................. 23
2.3.3 
Exploratory Objective Estimands .............................................................. 25 
3
POPULATION SAMPLES FOR ANALYSES .................................................... 27
4
SCHEDULE OF ANALYSES ............................................................................... 29
5 
SAMPLE SIZE AND POWER .............................................................................. 29 
6 
STATISTICAL METHODS .................................................................................. 29
6.1 
General Methods ................................................................................................ 29 
6.1.1 
Missing Data ................................................................................................. 30
6.1.2 
Type 1 Error Control ................................................................................... 30
6.1.3 
Subgroups ..................................................................................................... 31
6.1.3.1
Efficacy Subgroups for Evaluable mITT Subjects ............................. 31 
6.1.3.2
Safety Subgroups for Treated Subjects ............................................... 31
6.1.3.3
Safety Subgroups for DB or OL Rimegepant Treated Subjects........ 32
6.1.3.4
Safety Subgroups for OL Rimegepant Treated Subjects ................... 32
6.2 
Study Population ................................................................................................ 32 
6.2.1 
Population Samples for Analyses ............................................................... 32
6.2.2 
Enrollment .................................................................................................... 32
6.2.3 
Subject Disposition....................................................................................... 32
6.2.3.1 
Subject Disposition From Enrollment to Randomization .................. 33 
6.2.3.2 
Subject Disposition From Randomization to Treatment ................... 33 
6.2.3.3 
Subject Disposition in the DBT Phase .................................................. 33 
6.2.3.4 
Subject Disposition in the OLE Phase ................................................. 34
6.2.3.5 
Subject Disposition in the Follow-up Phase......................................... 35 
6.2.4 
Protocol Deviations ...................................................................................... 35 
6.2.5 
Pre-Treatment Characteristics ................................................................... 36
6.2.5.1
Demographics and Baseline Characteristics ....................................... 37
6.2.5.2
Medical History ...................................................................................... 38 
6.2.5.3
Migraine History .................................................................................... 38 


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6.2.5.4
Cardiac and Other Risk Factors .......................................................... 38
6.2.6 
Exposure ....................................................................................................... 38
6.2.6.1
Study Medication ................................................................................... 38
6.2.6.2
Drug Accountability............................................................................... 44
6.2.6.3
eDiary Compliance................................................................................. 46 
6.2.6.4
Non-Study Medications ......................................................................... 47
6.3 
Efficacy................................................................................................................ 48
6.3.1 
Reduction in Migraine Days per Month .................................................... 49
6.3.1.1 
Reduction in Migraine Days per Month in the DBT Phase: Primary 
Efficacy Endpoint................................................................................... 49 
6.3.1.2 
Reduction in Migraine Days per Month in the OLE Phase ............... 53
6.3.2 
Secondary Efficacy Endpoints .................................................................... 55
6.3.2.1 
Percentages of Subjects with Reduction in Migraine Days per Month
.................................................................................................................. 55
6.3.2.2 
Rescue Medication Days per Month .................................................... 58
6.3.2.3 
MSQoL in the DBT Phase ..................................................................... 59
6.3.2.4 
MIDAS in the DBT Phase ..................................................................... 60
6.3.2.5 
Overall Summary of Primary and Secondary Endpoints .................. 61 
6.3.3 
Exploratory Efficacy Endpoints ................................................................. 62
6.3.3.1
Reduction in MRM Days per Month ................................................... 62
6.3.3.2 
Reduction in Migraine Days in the First Week of the DBT Phase .... 65 
6.3.3.3 
Triptan or Ergotamine Days per Month ............................................. 66 
6.3.3.4 
Medication Days per Month on Non-Scheduled Days in the OLE 
Phase........................................................................................................ 68 
6.4 
Pharmacokinetic Evaluations ........................................................................... 69 
6.5 
Safety ................................................................................................................... 69 
6.5.1 
Adverse Events ............................................................................................. 70 
6.5.1.1 
Deaths ...................................................................................................... 70 
6.5.1.2 
AE Overviews ......................................................................................... 71 
6.5.1.3 
Pre-Treatment AEs ................................................................................ 72 
6.5.1.4 
On-Treatment AEs................................................................................. 72 
6.5.1.5 
Follow-up AEs ........................................................................................ 74 
6.5.1.6
AEs Across All Study Phases Combined ............................................. 74
6.5.1.7
Post-DBT Pre-OL Rimegepant AEs ..................................................... 74
6.5.2 
Laboratory Tests .......................................................................................... 75 
6.5.2.1 
Laboratory Test Abnormalities ............................................................ 75
6.5.2.2 
LFT Elevations ....................................................................................... 77
6.5.2.3 
Laboratory Test Changes From Baseline Over Time ........................ 78 
6.5.3 
Vital Signs and Physical Measurements .................................................... 79
6.5.3.1
Vital Sign and Physical Measurement Changes From Baseline Over 
Time ......................................................................................................... 79
6.5.3.2
Vital Sign and Physical Measurement Abnormalities ........................ 79
6.5.4 
Electrocardiograms...................................................................................... 80
6.5.4.1
ECG Changes From Baseline Over Time ............................................ 80
6.5.4.2
ECG Interpretation Shifts From Baseline to Worst Category .......... 80
6.5.4.3
ECG Abnormalities ............................................................................... 80


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6.5.5 
Sheehan-Suicidality Tracking Scale ........................................................... 81 
6.6 
Outcomes Research ............................................................................................ 81 
6.6.1 
MSQoL .......................................................................................................... 82 
6.6.2 
MIDAS .......................................................................................................... 82 
6.6.3 
CGI-c Scale ................................................................................................... 83
6.6.4 
PoM ............................................................................................................... 83 
6.6.5 
SM.................................................................................................................. 84
6.7 
COVID-19 Impact .............................................................................................. 84 
6.7.1 
COVID-19 Overall Impact .......................................................................... 84 
6.7.2 
COVID-19 Impact Over Time .................................................................... 84 
6.7.3 
COVID-19 Impact Listings ......................................................................... 85
7 
CONVENTIONS ..................................................................................................... 85 
7.1 
General ................................................................................................................ 85 
7.1.1 
Output Layout .............................................................................................. 85 
7.1.2 
Duplicate Subjects ........................................................................................ 86 
7.2 
Subgroups ........................................................................................................... 86 
7.3 
Derived Dates ..................................................................................................... 86 
7.4 
Analysis Periods ................................................................................................. 89 
7.5 
Analysis Visit Windows ..................................................................................... 91 
7.6 
Domain-Specific Derivations............................................................................. 93 
7.6.1 
Adverse Events ............................................................................................. 93 
7.6.2 
eDiary ............................................................................................................ 93 
7.6.2.1 
eDiary Reference Time Point Date and Epoch .................................... 93 
7.6.2.2 
eDiary Migraine Days ............................................................................ 95
7.6.2.3 
Scheduled and Non-Scheduled Days in the OLE Phase ..................... 96 
7.6.3 
Non-Study Medications ............................................................................... 98 
7.7 
Age at a Reference Date .................................................................................... 99 
8
CHANGES TO PLANNED ANALYSES IN THE PROTOCOL ...................... 99 
9
APPENDICES ....................................................................................................... 100
9.1 
COVID-19 Visit Impact ................................................................................... 100
9.1.1 
COVID-19 Visit Impact CRF Description ............................................... 100
9.1.2 
COVID-19 Impact ...................................................................................... 101 
9.1.3 
COVID-19 Visit Impact ............................................................................. 101 
9.1.4 
COVID-19 Premature Phase Termination .............................................. 101 
9.1.5 
COVID-19 Visit Impact Code ................................................................... 101 
9.1.5.1 
COVID-19 Visit Impact Code Derivation .......................................... 101 
9.1.5.2 
COVID-19 Visit Impact Code in Listings .......................................... 102 
 


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LIST OF TABLES 
Table 1:
Primary Objective Estimands ........................................................................... 23
Table 2: 
Secondary Objective Estimands ....................................................................... 24
Table 3:
Exploratory Objective Estimands .................................................................... 25
Table 4:
Analysis Visit Windows for Non-Efficacy Endpoints ..................................... 91
LIST OF FIGURES 
Figure 1: 
Study Schematic (Up to 12 Weeks of Double-blind Treatment with EOD 
Dosing, Followed by Up to 52 Weeks of Open-label Treatment with at Least 
EOD Dosing) ....................................................................................................... 22
 


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ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse event 
ALP 
Alkaline phosphatase  
ALT 
Alanine aminotransferase  
ASE 
Asymptotic standard error 
AST 
Aspartate aminotransferase  
BMI 
Body mass index 
CGI-c 
Clinical Global Impression - change 
CGRP 
Calcitonin gene-related peptide 
CI 
Confidence interval 
COVID-19 
Cornonavirus disease 2019 
CRF 
Case report form 
CSR 
Clinical study report 
CV 
Cardiovascular 
DB 
Double-blind 
DBT 
Double-blind treatment 
ECG 
Electrocardiogram 
eGFR 
Estimated glomerular filtration rate 
EOD 
Every other day 
EOFU 
End of follow-up 
EOT 
End of treatment 
HDL 
High-density lipoprotein  
IWRS 
Interactive web response system 
J2R 
Jump to reference 
LDL 
Low-density lipoprotein  
LFT 
Liver function test  
LLN 
Lower limit of normal 
LSM 
Least-squares mean 
MDRD 
Modification of diet in renal disease 
MIDAS 
Migraine Disability Assessment  
MR 
Menstrually-related 
MRM 
Menstrually-related migraine 
MSQoL 
Migraine Specific Quality of Life 
OL 
Open-label 
OLE 
Open-label extension 


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Abbreviation 
Definition 
OP 
Observational period 
OR
Outcomes research
POM 
Preference of medication 
PT 
Preferred term 
S-STS 
Sheehan-Suicidality Tracking Scale 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SI 
Systeme Internationale 
SOC 
System organ class 
SM 
Satisfaction with medication  
TEAE 
Treatment-emergent adverse event 
TBL 
Total bilirubin 
TLF 
Table, listing, and figure 
ULN 
Upper limit of normal  
US 
United States 
 


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REVISION HISTORY 
Version 
Description of Change 
1.0 
Original Issue 
2.0
 
General: Changed “during” to “in” when referring to DBT and OLE phases throughout 
document. Changed “rimegepant” to “DB or OL rimegepant” when referring to the DB or OL 
rimegepant phase, population, and study drug dates. Changed “dimension” to “domain” for 
MSQoL. 
 
Section 2.3.3: Removed “, Rimegepant Treated Subjects” from Table 3 OR endpoints. 
 
Section 6.1: Specified exceptions for treatment group displays in tables. 
 
Section 6.2.1: Added subsection titles and moved text for clarity. 
 
Section 6.2.3: Removed tables for enrolled subjects not in the mITT population. Added tables 
of demographics and baseline characteristics and migraine history for randomized subjects not 
in the mITT population. Added tables of demographics and rimegepant baseline 
characteristics for DB or OL rimegepant treated subjects by subgroup level and overall for all 
safety subgroups of interest specified in Section 6.1.3.  Added a table of prophylactic migraine 
medication use randomization strata for randomized subjects. 
 
Section 6.2.3.1: Added prophylactic migraine medication use randomization stratum to 
baseline characteristics. 
 
Section 6.2.3.2: Changed “rimegepant frequency” to “overall frequency”. 
 
Section 6.3.2.3: Specified that treatment group comparisons will be based on evaluable mITT 
subjects with MSQoL restrictive role function domain scores at both baseline and Week 12 of 
the on-DBT efficacy analysis period. 
 
Section 6.2.4.1: Added tables of eDiary DB or OL rimegepant exposure for DB or OL 
rimegepant treated subjects by subgroup level and overall for all safety subgroups of interest. 
Added time in follow-up for follow-up subjects to the table of eDiary study drug exposure. 
 
Section 6.2.4.2: Changed “study” to “study drug” in table of drug accountability compliance. 
 
Section 6.2.4.4: Added subsection titles and moved text for clarity. 
 
Section 6.3: Added 3 by-subject efficacy listings: subjects excluded from the efficacy analysis 
for randomized subjects not in the evaluable mITT population; primary and secondary 
efficacy endpoints for randomized subjects; exploratory endpoints for mITT subjects. 
 
Section 6.3.1: Specified additional details about 2 efficacy listings. 
 
Sections 6.3.1.1 and 6.3.2.1: Removed the phrase “(except prophylactic migraine medication 
use)”. 
 
Section 6.3.3.1: Specified additional details about the MRM day listing. 
 
Section 6.5: Replaced “EOS” with “EOFU” throughout section. 
 
Section 6.5.1.5: New section of “AEs Across All Study Phases Combined”. Moved text from 
Section 6.5. Added 1 table of all hepatic-related AEs leading to study drug discontinuation. 
 
Section 6.5.2.1: Moved text to Section 6.5.2.2. 
 
Section 6.5.2.2: Added subsection titles and moved text for clarity. Specified that exposure-
adjusted LFT elevations are multiple LFT elevation rates are assessed only for cumulative 
LFT elevations.  Specified additional details about eDISH plots. Moved text from Section 
6.5.2.1 about LFT ULN shifts from baseline. For by-subject longitudinal LFT plots, added 
subjects with ALP > 2 x ULN elevations and specified that treated migraine days will be 
displayed with symbols along the x-axis. 
 
Section 6.5.4.2: Modified section title. 


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Version 
Description of Change 
 
Section 6.5.4.3: Specified that ECG abnormalities will be summarized together with vital sign 
and physical measurement abnormalities in the same tables. 
 
Sections 6.6.3, 6.6.4, and 6.6.5: Removed baseline as a scheduled visit. 
 
Section 7.6.2: Defined treated migraine days. 
 
Section 7.3: Changed “last contact date/time” to “last contact date”. 
 
Section 7.4: Changed “last date/time” to “last date” for on-treatment and follow-up safety 
analysis periods. 
3.0 
 
General: Changed “populations for analyses” to “population samples for analyses”. Removed 
“survey” when referring to SM. Changed “95% normal CI” to “normal 95% CI”. Changed 
“SE” to “ASE” for binary efficacy endpoints. Changed “screening epoch” to “OP epoch”, 
“treatment epoch” to “DBT epoch”, and “extension epoch” to “OLE epoch”. 
 
Abbreviations: Added asymptotic standard error (ASE). 
 
Section 1.1: Changed protocol version from 4 to 7. 
 
Section 1.2.2: Modified the first objective to be based on moderate or severe migraines, and 
added an objective about comparing the change from baseline in the MIDAS total score at 
Week 12 of the DBT phase between rimegepant and placebo, as per Protocol Version 7. 
 
Section 1.2.3: Added 2 efficacy objectives, modified 5 existing efficacy objectives to be 
assessed by severity (total; moderate or severe), and updated language about MSQoL and 
MIDAS scores to align with Protocol Version 7. 
 
Section 2.3: Defined estimands and intercurrent events in greater detail. Modified Tables 1 to 
3 to (1) exclude “Population” rows and (2) display “Endpoint” instead of “Variables”. 
 
Section 2.3.2: Modified Table 2 to be consistent with changes to Section 1.2.2.  
 
Section 2.3.3: Modified Table 3 to be consistent with changes to Section 1.2.3. 
 
Section 6.1: Specified that exposure, efficacy, and safety results for the DBT phase will be 
presented only by treatment group without an overall column. 
 
Section 6.1.2: Modified bulleted list to be consistent with changes to Section 1.2.2. 
 
Section 6.1.3: Added a by-subject listing of efficacy and safety subgroups for treated subjects. 
 
Section 6.2.1.3: Added another category to the subject disposition in the DBT phase table per 
CRF Version 3. 
 
Section 6.2.4.1: Added parameters to the tables of DB or OL rimegepant exposure and study 
drug exposure. 
 
Section 6.2.4.4: Defined migraine standard or care medications. Revised the bulleted lists of 
tables. 
 
Section 6.3.1.1: Specified that the principal analysis of the primary endpoint will be repeated 
for moderate or severe migraine severity. 
 
Section 6.3.2.1: Specified that analyses will be stratified by severity (total; moderate or 
severe). Specified that subgroup analyses will be stratified by prophylactic migraine 
medication use at randomization. 
 
Section 6.3.2.3: Replaced text about calculating domain scores and imputing missing data 
with a reference to the BHV3000 Core SAP. Specified that 2-sided normal 95% CIs for mean 
change from baseline will also be presented in a descriptive analyses over time.  
 
Section 6.3.2.4: New section “MIDAS in the DBT Phase” added to address the new secondary 
objective in Section 1.2.2. Moved description of MIDAS from Section 6.6.2 to here. Cross-
referenced methodology in Section 6.3.2.3 and the BHV3000 Core SAP. 


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Version 
Description of Change 
 
Section 6.3.2.5: New section “Overall Summary of Primary and Secondary Endpoints” added 
to present the hierarchical testing of primary and secondary endpoints. 
Section 6.3.3.2: Specified that analyses will be repeated for moderate or severe migraine 
severity. 
 
Section 6.5.2: Specified that LDL cholesterol and triglycerides will be analyzed as separate 
laboratory test parameters by 8-hour fasting status with a reference to the BHV3000 Core 
SAP. 
 
Section 6.5.2.2: Added mutually exclusive elevations for TBL and ALP in LFT elevation 
summary. Replaced “treated migraine days” with “DBT and OL rimegepant dosing days” in 
by-subject longitudinal LFT plots. 
 
Section 6.5.5: Replaced the sentence “If the total score > 0, then responses to all questions will 
be presented; otherwise, only the ideation subscale, behavioral subscale, and total scores will 
be presented.” with a reference to the BHV3000 Core SAP for listing content. 
 
Section 6.6: Replaced the sentence about listing contents with a reference to the BHV3000 
Core SAP for contents of these listings. 
 
Section 6.6.1: Specified that 2-sided normal 95% CIs for mean change from baseline will also 
be presented in a descriptive analyses over time. 
 
Section 6.6.2: Moved description of MIDAS to new Section 6.3.2.4. Added absenteeism and 
presenteeism scores to descriptive analyses. Specified that 2-sided normal 95% CIs for mean 
change will also be presented in descriptive analyses over time. 
 
Section 6.6.3 through 6.6.5: Modified descriptions of rating scales to be consistent with the 
BHV3000 Core SAP. Specified that combined categories defined in the BHV3000 Core SAP 
will also be summarized in descriptive analyses over time. 
 
Section 7.5: Modified Table 4 by removing column for OR endpoints and using same visit 
windows as on-treatment safety for OR. 
 
Section 7.6.2.1: New section “eDiary Reference Time Point Date/Time and Epoch” added to 
define derivations for these 2 variables. 
 
Section 7.6.2.2: Removed sentence about treated migraine days. 
 
Section 7.6.3: New section “Non-Study Medications” added to define medication types. 
4.0 
 
Abbreviations: Removed “ATC”. 
 
Section 3: Added a table of inclusion and exclusion from the evaluable mITT sample 
population for randomized subjects. 
 
Section 6.2.4.1: Removed 3 references to epoch. 
 
Section 6.2.4.4: Replaced “ATC” with “therapeutic class”. 
 
Section 6.3: Added a reference to Section 3. Replaced “eDiary date” with “eDiary reference 
time point date” throughout. 
 
Section 6.5.2: Specified that LDL cholesterol and triglycerides will be assessed by fasting 
status rather than by 8-hour fasting status. Specified that the by-subject listing of LFT values 
and ratios to ULN will display all results over time for enrolled subjects with select LFT 
elevations (ALT or AST > 3 x ULN; ALP or TBL > 2 x ULN) at any time point. 
 
Section 7.3: Added eDiary reference date/time. Added definitions of DBT and OL rimegepant 
study drug date/times to be based on the Week 12 kit assigned date/time rather than epoch. 
Modified definitions of DBT and OL rimegepant start/end date/times, and OP start/end dates. 
Removed eDiary date. 
 
Section 7.4: Added new analysis periods for eDiary efficacy endpoints. Modified analysis 
periods for OR efficacy endpoints. 


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Version 
Description of Change 
 
Section 7.6.2.1: Modified the derivation of epoch to be based on the DBT and OL rimegepant 
start dates.  
Section 7.6.2.2: Added 1 more criterion to determine whether a headache lasted 30 minutes. 
Added text to clarify the use of finding date/time for determining whether a headache lasted  
30 minutes and on determining multiple migraine characteristics. Revised text about 
determining migraine date. Removed text about counting a migraine day as 2 days. 
5.0 
 
Abbreviations: Added LSM. 
 
Section 1.1: Changed Protocol Version from 7 to 8.0. 
 
Section 1.2: Aligned objectives with Protocol Version 8.0. 
 
Section 2.3.1 to 2.3.3: Aligned objectives and estimands in Tables 1, 2, and 3 with Protocol 
Version 8.0. 
 
Section 3: Defined interim subjects. 
 
Section 6.1: Specified that interim subjects will be assessed by as-treated treatment group. 
 
Section 6.1.2: Aligned endpoints with Protocol Version 8.0. 
 
Section 6.2.2: Changed “treated subjects” to “randomized subjects”. 
 
Section 6.2.4.1: Changed “4 weeks” to “month” throughout section. 
 
Sections 6.3: Changed “4 weeks” and “interval” to “month” throughout section. Changed 
“mean” to “LSM” throughout section in treatment group comparisons. Combined the by-
subject listing of primary and secondary efficacy endpoints. 
 
Section 6.3.1.1:  
o 
Descriptive Analyses: Changed y-axis of scatter plots to be on change instead of 
reduction, and consistent with primary objective. 
o 
Principal Analysis: Clarified which GLMEM results supported primary, secondary, versus 
exploratory objectives. Removed mean values by visit from model estimates. Specified 
that the model will be repeated by prophylactic migraine medication use at randomization. 
Added 2 longitudinal plots of LSM changes from OP in the number of migraine days per 
month by severity (total; moderate or severe) versus month. 
o 
Subgroup Analyses: Specified that subgroup analyses of the primary endpoint will not 
include prophylactic migraine medication use at randomization in the model. Removed 
mean values by visit from model estimates. 
 
Section 6.3.1.2: Descriptive Analyses: Changed y-axis of scatter plots to be on change instead 
of reduction. Specified that results will support the exploratory objective about OLE phase 
efficacy. Added 2 longitudinal plots of mean changes from OP in the number of migraine days 
per month by migraine severity (total; moderate or severe) versus month. 
 
Section 6.3.2.1:  
o 
Replaced 2 paragraphs with text defining responders and failures. 
o 
DBT Descriptive Analyses: Specified that analyses by month will be presented using 2 
methods, Non-Evaluable = Failure and Non-Evaluable = Missing. Removed the “< 1” 
reduction category. Added 3 tables of percentage of subjects with reduction outcomes by 
migraine severity (total; moderate or severe) for each select percentage reduct
.  


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Statistical Analysis Plan for Protocol BHV3000-305 
Page 13 of 102
Version 
Description of Change 
o 
DBT Phase Treatment Group Comparisons: Specified that response rates will be based 
on responder outcomes described previously. Specified that results will support the 
secondary and exploratory objectives about percent reductions. Specified that endpoints 
will also be compared between treatment groups using unstratified CMH tests for each 
subgroup level; removed “stratified” from 2 bullets. Added 6 longitudinal plots of 
percentage of subjects with reduction versus month 
. 
o 
OLE Phase: Specified that analyses by month will be presented using 2 methods, Non-
Evaluable = Failure and Non-Evaluable = Missing. Specified that results will support the 
exploratory objective about OLE phase efficacy.  
 
Section 6.3.2.2: DBT Phase Treatment Group Comparisons: Clarified which GLMEM results 
supported secondary versus exploratory objectives. Specified that the model will be repeated 
by prophylactic migraine medication use at randomization. 
 
Sections 6.3.2.3 and 6.3.2.4: DBT Phase Treatment Group Comparisons: Changed GLMEM 
to GLM and removed subject as a random effect from the model. Removed mean values by 
visit from model estimates. Specified that the model will be repeated by prophylactic migraine 
medication use at randomization. 
 
Section 6.3.2.5: Aligned endpoints with Protocol Version 8.0. 
 
Section 6.3.3.1: DBT Phase Treatment Group Comparisons: Specified that the model will be 
repeated by prophylactic migraine medication use at randomization. 
 
Section 6.3.3.2: Treatment Group Comparisons: Changed GLMEM to GLM and removed 
subject as a random effect from the model. Specified that the model will be repeated by 
prophylactic migraine medication use at randomization. Removed mean values from model 
estimates. 
 
Section 6.5: Added post-DBT pre-OL rimegepant to the list of safety analysis periods. 
Specified that measurements will be slotted into analysis periods based on “measurement 
dates”, which are (1) imputed start dates for AEs, and (2) collection or assessment dates for all 
other safety parameters. 
 
Section 6.5.1.1: Added an overall AE summary table during post-DBT pre-OL rimegepant for 
interim subjects. 
 
Section 6.5.1.6: New section “Post-DBT Pre-OL Rimegepant AEs”. Added 3 tables of AEs 
during post-DBT pre-OL rimegepant for interim subjects. 
 
Section 6.5.2.1: Added a table of worst laboratory test abnormalities during post-DBT pre-OL 
rimegepant for interim subjects. 
 
Section 6.5.2.2: Added a table of LFT elevations during post-DBT pre-OL rimegepant for 
interim subjects. Removed 2 tables of multiple cumulative LFT elevation rates assessed as 
continuous parameters. 
 
Section 6.6: Specified that measurements will be slotted into analysis periods according to 
assessment dates. 
 
Section 7.4: Changed “interim efficacy” to “post-DBT pre-OL rimegepant efficacy”. Modified 
the definition of the on-DBT safety analysis period. Defined the post-DBT pre-OL rimegepant 
safety analysis period. 
 
Section 7.6.1: Modified the definition of the on-DBT safety analysis period. 
 
Section 7.6.3: Modified the definition of DBT concomitant non-study medications. 


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Statistical Analysis Plan for Protocol BHV3000-305 
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Version 
Description of Change 
6.0
 
Section 6.2.4.1: Replaced “study medication” with “study drug” where applicable. Specified 
that imputed OL rimegepant to treat headache date/time will be derived for subjects who 
answer “yes” to the question about having already taken study medication to treat a headache 
on the eDiary scheduled dosing report, but do not have study drug data from any other eDiary 
source on the same day. Specified that subjects with non-missing imputed OL rimegepant to 
treat headache date/times will be credited with taking 1 tablet of OL rimegepant on each of 
those days to account for missed OL rimegepant exposure from eDiary non-compliance. 
 
Section 6.3.2.1: Added another category to the outcomes table. 
 
Section 7.3: Defined imputed OL rimegepant to treat headache date/time, and added it to the 
derivation of study drug date/time. Specified that the reference date from the medication 
reconciliation form is compared with the IWRS Week 12 kit assigned date. 
 
Section 7.6.2.2: Added imputed OL rimegepant to treat headache date/time to the derivation of 
item 2a. 
7.0 
 
Abbreviations: Added eGFR, LLN, and MDRD. 
 
Section 3: Moved text about tables and listings to Section 6.2.1. 
 
Section 6.1.3: Modified subgroup levels of historical number of moderate or severe migraine 
attacks per month. Removed the cumulative rimegepant exposure subgroup and the by-subject 
listing of efficacy and safety subgroups. Removed subsequent references to safety subgroups 
of interest throughout. 
 
Section 6.2.1: New section “Population Samples for Analyses”. Moved text from Section 3 
here. 
 
Section 6.2.2: New section “Enrollment”. Added 3 tables: enrollment by country and site; 
enrollment by age group; accrual by randomization year and month. 
 
Section 6.2.3.3: Replaced “mITT” with “evaluable mITT”. 
 
Section 6.2.5: Modified the derivation of age at rimegepant baseline. Removed birth date from 
the demographics listing. Replaced “mITT” with “evaluable mITT”. Modified the listing of 
baseline characteristics. 
 
Section 6.2.5.1: Removed the derivation of age at informed consent. Added country to 
demographics.  
 
Section 6.2.5.3: Modified the contents of the migraine history table. 
 
Section 6.2.6.1: Specified multiple sources of study drug in the eDiary. Modified the contents 
of eDiary exposure tables. Modified the formulas for total study drug exposure and time in 
follow-up. 
 
Section 6.2.6.2: Added 1 table of eDiary versus drug accountability cumulative exposure. 
 
Section 6.2.6.3: Modified the contents of eDiary compliance tables. 
 
Section 6.3.1.1: Added “through Month 3” to the definition of the overall DBT mean. 
 
Section 6.3.1.2: Added “through Month 13” to the definition of the overall OL rimegepant 
mean. 
 
Sections 6.3.2.2 and 6.3.3.1: Added “through Month 3” to the definition of the overall DBT 
mean. Added “through Month 13” to the definition of the overall OL rimegepant mean. 
 
Section 6.3.2.3: Removed EOT. 
 
Section 6.5.2: Specified that eGFR will be calculated using the MDRD formula and an LLN 
of 60. Added a by-subject listing of local laboratory CK fractionation. 
 
Section 7.1.2: New section “Duplicate Subjects”. 
 
Section 7.2: Replaced text with “Not applicable”. 


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Statistical Analysis Plan for Protocol BHV3000-305 
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Version 
Description of Change 
 
Section 7.7: New section “Age at a Reference Date”. 
8.0 
 
Signature page: Replaced 
 with 
, and 
 with 
. 
 
Abbreviations: Added COVID-19. 
 
General: Changed “rimegepant baseline” to “DB or OL rimegepant baseline” throughout. 
Changed references to Section 6.1.3 to Section 6.1.3.1. 
 
Section 3: Defined COVID-19 impacted subjects. 
 
Section 6.1: Specified that all by-subject listings except administrative listings will identify 
subjects impacted by COVID-19. 
 
Section 6.1.3: Moved text to new subsection 6.1.3.1 “Efficacy Subgroups for Evaluable mITT 
Subjects”. Added subsections 6.1.3.2, 6.1.3.3, and 6.1.3.4.  
 
Section  6.1.3.1: Modified subgroup levels for historical number of moderate or severe 
migraine attacks per month and historical chronic migraine. 
 
Section 6.2.3: Specified that listings for the OLE and follow-up phases will identify subjects 
who terminated the phase prematurely due COVID-19. 
 
Section 6.2.3.3: Modified definitions of completed DBT phase, did not complete DBT phase, 
and completed DBT phase but not continuing to OLE phase. Added tables of subject 
disposition in the DBT phase for treated subjects by safety subgroup level and overall for each 
treatment group. 
 
Section 6.2.3.4: Modified definitions of completed OLE phase and did not complete OLE 
phase. Added reasons for premature OLE phase termination to the subject disposition table. 
Added tables of subject disposition in the OLE phase for OL rimegepant treated subjects by 
subgroup level and overall for all safety subgroups of interest. 
 
Section 6.2.3.5: Added reasons for premature follow-up phase termination to the subject 
disposition table. 
 
Section 6.2.5: Added the following tables: (1) demographics and baseline characteristics by 
safety subgroup level and overall for treated subjects; (2) migraine history for DB or OL 
rimegepant treated subjects by treatment group and overall; (3) demographics and baseline 
characteristics, migraine history, and cardiac and other risk factors by safety subgroup level 
and overall for DB or OL rimegepant treated subjects and OL rimegepant treated subjects. 
Defined age at OL rimegepant baseline and OL rimegepant baseline. 
 
Section 6.2.6.1: Specified that the listing of eDiary exposure and drug accountability will 
display COVID-19 visit impact code for visits impacted by COVID-19. Added eDiary 
exposure tables by safety subgroup level and overall for treated subjects, DB or OL 
rimegepant treated subjects, and OL rimegepant treated subjects. Modified contents of 
exposure tables. Modified the definition of study discontinuation. 
 
Section 6.2.6.2: Changed “>” to “ ” in eDiary versus drug accountability cumulative exposure 
table. Added methods for the drug accountability compliance table. 
 
Section 6.2.6.4: Section 6.2.6.1: Specified that non-study medication listings will display 
COVID-19 visit impact code for visits impacted by COVID-19. Added the following tables: 
(1) non-study prophylactic migraine standard of care medications for mITT subjects with 
prophylactic migraine medication use at randomization; (2) non-study concomitant 
medications by safety subgroup level and overall for DB or OL rimegepant treated subjects 
and OL rimegepant treated subjects. 
 
Section 6.3.1: Specified that the listing of eDiary evening report and follow-up headache logs 
will display COVID-19 visit impact code for visits impacted by COVID-19. 
PPD
PPD
PPD
PPD


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Statistical Analysis Plan for Protocol BHV3000-305 
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Version 
Description of Change 
 
Section 6.3.2.1: Added reduction categories to descriptive tables of reductions from the OP
over time during DBT and OLE. Added a category “Not evaluable” to Not Evaluable = 
Failure analyses by month. Specified that analyses for the Non-Evaluable = Failure method 
during the OLE phase will only be shown in the Addendum Report. 
 
Section 6.3.3.1: Specified that the menstrual periods listing will display COVID-19 visit 
impact code for visits impacted by COVID-19. 
 
Section 6.3.3.3: New section “Triptan or Ergotamine Days per Month”. Added 3 tables. 
 
Section 6.3.3.4: New section “Medication Days per Month on Non-Scheduled Dosing Days in 
the OLE Phase”. Added 1 table. 
 
Section 6.5: Specified that safety listings will display COVID-19 visit impact code for visits 
impacted by COVID-19. 
 
Section 6.5.1: Defined TEAEs on OL rimegepant. 
 
Section 6.5.1.1: Added tables of AE overviews by safety subgroup level and overall for DB or 
OL rimegepant treated subjects and OL rimegepant treated subjects. 
 
Section 6.5.1.3: Added AE tables by safety subgroup level and overall for treated subjects, DB 
or OL rimegepant treated subjects, and OL rimegepant treated subjects. 
 
Section 6.5.1.2: Added laboratory test tables by safety subgroup level and overall for treated 
subjects, DB or OL rimegepant treated subjects, and OL rimegepant treated subjects. 
 
Section 6.5.2: Specified which laboratory test listings will display COVID-19 visit impact 
code for visits impacted by COVID-19. 
 
Section 6.5.2.2: Added LFT tables by safety subgroup level and overall for DB or OL 
rimegepant treated subjects and OL rimegepant treated subjects. Added eDISH plots by 
mutually-exclusive safety subgroup level for DB or OL rimegepant treated subjects and OL 
rimegepant treated subjects. 
 
Sections 6.5.3.2, 6.5.4.2, and 6.5.4.3: Added tables by safety subgroup level and overall for 
DB or OL rimegepant treated subjects and OL rimegepant treated subjects. 
 
Section 6.6: Specified that OR listings will display COVID-19 visit impact code for visits 
impacted by COVID-19. 
 
Sections 6.6.1 and 6.6.2: Added 7 tables of treatment group comparisons of MSQOL and 
MIDAS score changes from baseline at Week 12 of DBT OR analysis period for treated 
subjects.  
 
Section 6.7: New section “COVID-19 Impact”. Added 3 tables and 2 listings. 
 
Section 7.3: Replaced “Week 12 kit assigned” with “Week 12 kit assigned local”. Modified 
the definitions of OL rimegepant last date/time, eDiary efficacy date/time, and last contact 
date. Defined the COVID-19 visit date. 
 
Section 7.5: Defined randomization days. Modified the title and contents of Table 4. 
 
Section 9: New section “Appendices”. 
 
Section 9.1: New section “COVID-19 Visit Impact”. 
9.0 
 
General: Changed “CGI-C” to “CGI-c”. 
 
Sections 2.3.3, 6.3.2.4, and 6.6.2: Removed the MIDAS lost productivity time score. 
 
Sections 6.2.2, 6.2.5.1, 6.2.5.3, and 6.2.5.4: Replaced text with reference to the BHV3000 
Core SAP. 
 
Section 6.2.6.1: Added patient-years of exposure to tables of eDiary rimegepant or placebo 
exposure during double-blind treatment and eDiary OL rimegepant exposure. 
 
Section 6.5: Specified that deaths are slotted into analysis periods according to the death date. 


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Statistical Analysis Plan for Protocol BHV3000-305 
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Version 
Description of Change 
 
Section 6.5.1: Moved text about deaths to new Section 6.5.1.1. Renumbered subsections.
 
Section 6.5.1.1: New section “Deaths”. Added a table of deaths. Specified contents of the 
deaths listing. 
 
Section 6.5.1.2: Removed AE leading to death from AE overview tables. 
 
Section 6.5.1.4:  
o 
DBT Phase: Changed “in  X% of subjects” to “with  X% frequency”. Removed 2 tables 
of exposure-adjusted AEs. Added tables of exposure-adjusted multiple occurrences of 
unique AEs. 
o 
DB or OL Rimegepant Phase: Removed all tables of exposure-adjusted AEs. Added  
tables of AEs occurring with  5% frequency by severity and exposure-adjusted multiple 
occurrences of unique AEs. 
o 
OLE Phase: Added tables of AEs occurring with  5% frequency by severity and 
exposure-adjusted multiple occurrences of unique AEs.  
 
Section 6.5.2: Replaced the eGFR MDRD formula with a reference to the BHV3000 Core 
SAP. 
 
Sections 6.5.2.1, 6.5.2.2, 6.5.3.2, 6.5.4.3, and 6.5.5: Replaced text with references to the 
BHV3000 Core SAP. 
 
Section 7.3: Modified the derivation of the last contact date. Added the death date. 
 
Section 7.6.1: Changed “exposure-adjusted AEs” to “exposure-adjusted multiple occurrences 
of unique AEs”. 
10.0 
Modified after the final database lock for the Addendum Report to correct errors and make analyses 
consistent. 
 
General: Replaced “Interim Week 12 CSR” with “CSR” and “final CSR” with “Addendum 
Report”. 
 
Sections 1.1 and 7.1.1: Specified the Addendum Report. 
 
Sections 3 and 6.3.3.1: Replaced “evaluable mITT menstruating female subjects” with 
“menstrual migraine evaluable mITT menstruating female subjects”, and “evaluable OL 
rimegepant mITT menstruating female subjects” with “menstrual migraine evaluable OL 
rimegepant mITT menstruating female subjects”. Defined these 2 new cohorts to align MRM 
days per month analyses with migraine days per month analyses. 
 
Section 6.3.3.4: Changed section title to “Medication Days per Month on Non-Scheduled Days 
in the OLE Phase”. Removed text about sources of rimegepant and the definition of non-
scheduled dosing days. Added a reference to Section 7.6.2.3. Replaced “non-scheduled dosing 
day” with “non-scheduled day”. 
 
Section 7.3: Modified definition of efficacy date. 
 
Section 7.6.2.2: Modified criterion 2a for no qualified migraine headache. 
 
Section 7.6.2.3: New section “Scheduled and Non-Scheduled Days in the OLE Phase”. Defined 
scheduled and non-scheduled days in the OLE phase, and provided an example. 


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1 INTRODUCTION AND OBJECTIVES OF ANALYSIS 
1.1
Introduction
This document presents the statistical analysis plan (SAP) for Biohaven Pharmaceuticals, 
Protocol BHV3000-305: A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to 
Evaluate the Efficacy and Safety of Rimegepant in Migraine Prevention. 
This SAP is based on BHV3000-305 Protocol Version 8.0, and describes the analysis of the 
double-blind treatment (DBT), open-label extension (OLE), and follow-up phases of the study. 
It contains analysis details and methodology to answer the study objectives, including planned 
summary tables, by-subject listings, and figures, which will provide the basis for the results 
section of the 90-Day Safety Update, CSR, and Addendum Report. Operational aspects related 
to collection and timing of planned clinical assessments are not repeated in this SAP unless 
relevant to the planned analyses.  
1.2 
Study Objectives 
1.2.1 
Primary Objectives 
To compare the efficacy of rimegepant to placebo as a preventive treatment for migraine, as 
measured by the reduction from baseline in the mean number of migraine days per month in the 
last 4 weeks of the DBT phase (a month is defined as 4 weeks for the purpose of this protocol). 
1.2.2 
Secondary Objectives 
 
To compare the efficacy of rimegepant to placebo on the proportion of subjects who 
have at least a 50% reduction from baseline in the mean number of moderate or severe 
migraine days per month in the last 4 weeks of the DBT phase. 
 
To compare the efficacy of rimegepant to placebo on the reduction from baseline in the 
mean number of migraine days per month over the entire course of the double-blind 
treatment phase. 
 
To compare the frequency of use of rescue medications between rimegepant and placebo 
in the last 4 weeks of the DBT phase.  
 
To compare the efficacy of rimegepant to placebo on the reduction from baseline in the 
mean number of migraine days per month in the first 4 weeks of the DBT phase. 
 
To evaluate the safety and tolerability of rimegepant. 
 
To evaluate the frequency of alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 3x upper limit of normal (ULN) with concurrent elevations in 
total bilirubin (TBL) > 2x ULN in subjects treated with rimegepant. 
 
To evaluate the frequency of hepatic-related adverse events (AEs) and hepatic-related 
treatment discontinuations in subjects treated with rimegepant. 


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To compare the change from baseline in the Migraine-Specific Quality-of-Life 
Questionnaire (MSQoL) v2.1 restrictive role function domain score at Week 12 of the 
DBT phase between rimegepant and placebo. 
 
To compare the change from baseline in the Migraine Disability Assessment (MIDAS) 
total score at Week 12 of the DBT phase between rimegepant and placebo. 
1.2.3 
Exploratory Objectives 
 
To compare the efficacy of rimegepant to placebo on the reduction from baseline in the 
mean number of migraine days per month by severity (total; moderate or severe) in each 
month and the entire course of the DBT phase. 
 
To compare the efficacy of rimegepant to placebo on the proportion of subjects who 
have at least a 50% reduction from baseline in the mean number of migraine days per 
month by severity (total; moderate or severe) in each month and the entire course of the 
DBT phase. 
 
To evaluate the reduction in the number of migraine days per month by severity (total; 
moderate or severe) in each month and the entire course of the OLE phase.  
 
To compare the efficacy of rimegepant to placebo as a preventive treatment for 
menstrually-related migraine (MRM), as measured by the reduction from baseline in the 
mean number of MRM days per month in each month and the entire course of the DBT 
phase. 
 
To compare the efficacy of rimegepant to placebo on the proportion of subjects who 
have at least a 75% reduction from baseline in the mean number of migraine days per 
month by severity (total; moderate or severe) in each month and the entire course of the 
DBT phase. 
 
To compare the efficacy of rimegepant to placebo on the proportion of subjects who 
have a 100% reduction from baseline in the mean number of migraine days per month by 
severity (total; moderate or severe) in each month and the entire course of the DBT 
phase. 
 
To evaluate the frequency of elevated liver function tests (LFT: AST, ALT, or TBL) in 
subjects treated with rimegepant. 
 
To evaluate the frequency of subjects with ALT or AST elevations > 3x ULN in 
temporal association with nausea, vomiting, anorexia, abdominal pain, or fatigue in 
subjects treated with rimegepant. 
 
To evaluate the effect of rimegepant treatment on the MSQoL v2.1 domain scores. 
 
To evaluate the effect of rimegepant treatment on the Migraine Preference of Medication 
(PoM). 
 
To evaluate the effect of rimegepant treatment on the Satisfaction with Medication (SM). 
 
To evaluate the effect of rimegepant treatment on the MIDAS scores. 


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Statistical Analysis Plan for Protocol BHV3000-305 
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To evaluate the effect of rimegepant treatment on the Clinical Global Impression of 
Change (CGI-c) scale. 
 
To compare the efficacy of rimegepant to placebo on the reduction from baseline in the 
mean number of migraine days per week by severity (total; moderate or severe) in the 
first week of the DBT phase. 
 
To compare the frequency of use of rescue medications between rimegepant and placebo 
in each month and the entire course of the DBT phase. 
2 STUDY DESIGN 
2.1 
Synopsis of Study Design 
BHV3000-305 is a multicenter, randomized, double-blind, placebo-controlled study to assess 
the efficacy and safety of rimegepant in migraine prevention with DBT, OLE, and follow-up 
phases. 
The screening phase includes a screening visit and a 28-day observational period (OP) of 
standard care. For subjects to be eligible for the study, they must report having had 4-18 
migraine attacks of moderate to severe intensity per month in the 3 months prior to the 
screening visit, and at least 6 migraine days and no more than 18 headache days during the 28-
day OP which will be documented in the electronic diary (eDiary).  
After providing informed consent, patients will first participate in the screening phase to 
determine eligibility for the study. Upon completion of the screening visit, subjects will be 
provided an eDiary to document each day of the 28-day OP if a migraine occurred, the migraine 
intensity, and if the migraine was treated. Subjects will record the standard of care migraine 
treatment received on a paper diary and female subjects will record their menstrual period 
information on a paper log. 
Subjects will have blood drawn for baseline lab profiles at the pre-randomization laboratory 
visit; this visit must occur within 96 hours (4 days) of the baseline visit. Subjects will then 
return for the baseline visit. 
After completing the 28-day OP and the pre-randomization laboratory visit, patients will return 
to the study site for their baseline visit where eligibility for continued participation in the study 
will be assessed prior to randomization and dispensement of study medication. After the 
investigator reviews the results of the pre-randomization laboratory visit and determines 
continued eligibility, the site staff will inform the patient whether or not they are eligible to start 
dosing. If eligible, subjects will be instructed that they must take one tablet of blinded study 
medication (rimegepant or placebo) every other day (EOD). If subjects have a migraine during 
the DBT phase of the study, if needed, they may treat the migraine with their standard of care 
medication and continue to take blinded study medication on their regular EOD schedule 
(scheduled dosing days only). Refer to BHV3000-305 Protocol Table 1: Schedule of 
Assessments – Double-Blind Treatment. 


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At the completion of the 12-week DBT phase, subjects may be entered into the 52-week OLE 
phase following laboratory test results are within acceptable ranges per protocol. During the 
OLE phase, subjects will be instructed that they must take one tablet of open-label (OL) 
rimegepant EOD. If subjects have a migraine on a day that they are not scheduled to dose with 
study drug, then they may take one tablet of OL rimegepant on that calendar day to treat a 
migraine. Thus, during the OLE phase, subjects can take a maximum of one tablet of study drug 
per calendar day for this 52-week period. Refer to BHV3000-305 Protocol Table 2: Schedule of 
Assessments – Open-Label Extension Phase Including End of Treatment (EOT) and Follow-up 
Visits. 
Study visits will occur at screening (enrollment), pre-randomization lab visit (which must occur 
within 96 hours of the baseline visit), baseline (randomization), Weeks 2, 4, 8, and 12. At the 
completion of the 12-week DBT phase, subjects may enter into the 12-week OLE phase if they 
continue to meet study entry criteria and laboratory test results are acceptable per protocol. 
During the OLE phase, visits occur at Weeks 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 
and 64/EOT. Subjects will return to the study site at the end of Week 64 for the EOT visit. 
There is also a 2-Week and 8-Week follow-up visit 14 days and 8 weeks after the EOT visit, 
respectively, for assessment of LFTs. Subjects who do not complete the DBT phase and/or do 
not enter or complete the OLE phase should complete the EOT visit, the 2-Week or the 8-Week 
safety follow-up visit. 
2.2 
Randomization Methodology 
After the completion of the 28-day OP, subjects will enter the DBT phase and up to 
approximately 800 eligible subjects will be randomized to receive rimegepant or placebo with 
an EOD dosing schedule. Subjects will be randomized in a 1:1 ratio to rimegepant or placebo 
treatment groups, stratified by current use of prophylactic migraine medication (yes or no). It is 
estimated that approximately 675 subjects will enter the OLE phase. Subject numbers, treatment 
group, and study medication will be assigned via the Interactive Web Response System (IWRS). 
A by-subject administrative listing of randomization scheme and codes will be provided for all 
randomization numbers and block numbers, even those not assigned to a subject. This listing 
will be sorted by randomization number and block number. 
 


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Figure 1: 
Study Schematic (Up to 12 Weeks of Double-blind Treatment with EOD Dosing, Followed by Up to 52 
Weeks of Open-label Treatment with at Least EOD Dosing)   
 


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2.3
Study Estimands
An estimand is the target of estimation to address the scientific question of interest posed by a 
study objective. The four attributes of an estimand include the population of interest, endpoint of 
interest, specification of how intercurrent events are reflected in the scientific question of 
interest, and the population-level summary for the endpoint. 
For all objectives, the population of interest is defined through appropriate inclusion/exclusion 
criteria to reflect the targeted patient population for approval. Refer to the BHV3000-305 
Protocol for inclusion/exclusion criteria. 
Intercurrent events are those that occur after treatment initiation and either preclude observation 
of the endpoint or affect its interpretation. The following will be considered intercurrent events: 
 
Study drug discontinuation before the time point of interest defining the endpoint. For 
efficacy and safety objectives, study drug discontinuation will be handled with a while-
on-treatment strategy, i.e., response to treatment prior to the occurrence of the 
intercurrent event of interest, such that all observed values of the endpoint of interest will 
be used prior to study drug discontinuation. For outcomes research objectives, study drug 
discontinuation will be handled with a treatment policy strategy, i.e., the occurrence of 
the intercurrent event will be considered irrelevant, such that all observed values of the 
endpoint of interest will be used regardless of study drug discontinuation. 
 
Use of non-study migraine standard of care medications on or before the time point of 
interest. For all objectives, this intercurrent event will be handled with a treatment policy 
strategy, such that all observed values of the endpoint of interest will be used.   
2.3.1 
Primary Objective Estimands 
The estimands corresponding to the primary endpoint for this study are shown in Table 1.  
Table 1: 
Primary Objective Estimands 
Objective
Reduction in the mean number of migraine days per month in the last 4 weeks 
of the DBT phase – Efficacy 
Endpoint 
Change from OP in the mean number of migraine days per month on treatment in 
the last month (Weeks 9 to 12) of the DBT phase 
Pop. Summary 
Change from OP by treatment group using descriptive statistics and model, and 
difference between treatment groups from model 
2.3.2 
Secondary Objective Estimands 
The estimands corresponding to the secondary objectives are shown in Table 2. 


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Table 2: 
Secondary Objective Estimands 
Objective 
Proportion of subjects 
moderate or severe migraine 
days per month in the last 4 weeks of the DBT phase – Efficacy 
Endpoint
Number and p
from OP in the mean 
number of moderate or severe migraine days per month on treatment in the last month 
of the DBT phase  
Pop. Summary 
Frequency by treatment group and difference in percentages between treatment groups 
Objective 
Reduction from baseline in the mean number of migraine days per month over 
the entire course of the DBT phase – Efficacy 
Endpoint 
Change from baseline in the mean number of migraine days per month over the entire 
double-blind treatment phase (Weeks 1 to 12) 
Pop. Summary 
Change from OP by treatment group using descriptive statistics and model, and 
difference between treatment groups from model 
Objective 
Frequency of use of rescue medication days per month in the last 4 weeks of the 
DBT phase – Efficacy 
Endpoint 
Mean number of rescue medication days per month on treatment in the last month of 
the DBT phase 
Pop. Summary 
Value by treatment group using descriptive statistics and model, and difference 
between treatment groups from model 
Objective 
Reduction from baseline in the mean number of migraine days per month in the 
first 4 weeks of the DBT phase – Efficacy 
Endpoint 
Change from OP in the mean number of migraine days per month on treatment in the 
first month (Weeks 1 to 4) of the DBT phase 
Pop. Summary 
Change from OP by treatment group using descriptive statistics and model, and 
difference between treatment groups from model 
Objective 
Safety and Tolerability  
Endpoint 
Percentage of subjects with AEs, serious AEs (SAE), AEs leading to study drug 
discontinuation, and clinically significant laboratory abnormalities on treatment in the 
DBT and OLE phases 
Pop. Summary 
Frequency by treatment group and overall 
Objective 
Concurrent LFT elevations – Safety 
Endpoint 
Number and percentage of subjects with ALT or AST > 3 x ULN concurrent with 
elevations in TBL > 2 x ULN on treatment in the DBT and OLE phases 
Pop. Summary 
Frequency by treatment group and overall 
Objective 
Hepatic-related AEs – Safety 
Endpoint 
Number and percentage of subjects with hepatic-related AEs and hepatic-related AEs 
leading to study drug discontinuation on treatment in the DBT and OLE phases 
Pop. Summary 
Frequency by treatment group and overall 


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Objective 
MSQoL restrictive role function domain score change from baseline at Week 12 – 
Efficacy 
Endpoint
Change from baseline in the MSQoL restrictive role function domain score at Week 12
in the DBT phase 
Pop. Summary 
Change from baseline by treatment group using descriptive statistics and model, and 
difference between treatment groups from model 
Objective 
MIDAS total score change from baseline at Week 12 – Efficacy 
Endpoint 
Change from baseline in the MIDAS total score at Week 12 in the DBT phase 
Pop. Summary
Change from baseline by treatment group using descriptive statistics and model, and 
difference between treatment groups from model 
2.3.3 
Exploratory Objective Estimands 
The estimands corresponding to the exploratory objectives are shown in Table 3. 
Table 3: 
Exploratory Objective Estimands 
Objective 
Reduction in the mean number of migraine days per month by migraine severity 
(total; moderate or severe) in each month and the entire course of the DBT phase 
– Efficacy 
Endpoint 
Change from OP in the mean number of migraine days per month on treatment by 
migraine severity in each month and overall in the DBT phase 
Pop. Summary 
Change from OP by treatment group using descriptive statistics and model, and 
difference between treatment groups from model 
Objective 
Proportion of subjects who have 
by 
migraine severity (total; moderate or severe) in each month and the entire course 
of the DBT phase – Efficacy 
Endpoint
in the mean 
number of migraine days per month on treatment by migraine severity in each month 
and overall in the DBT phase  
Pop. Summary
Frequency by treatment group and difference in percentages between treatment groups 
Objective 
Reduction in the number of migraine days per month by migraine severity (total; 
moderate or severe) in each month and the entire course of the OLE phase – 
Efficacy 
Endpoint 
(1) Change from OP in the mean number of migraine days per month and (2) number 
and percentage of subjects who have  
from OP in the 
mean number of migraine days per month, on treatment by migraine severity in each 
month and overall in the OLE phase 
Pop. Summary 
Change from OP and frequency by treatment group and migraine severity using 
descriptive statistics 


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Objective 
Reduction in the mean number of MRM days per month in each month and the 
entire course of the DBT phase – Efficacy 
Endpoint
Change from OP in the mean number of MRM days per month on treatment in each 
month and overall in the DBT phase 
Pop. Summary 
Change from OP by treatment group using descriptive statistics and model, and 
difference between treatment groups from model 
Objective 
month by 
migraine severity (total; moderate or severe) in each month and the entire course 
of the DBT phase – Efficacy 
Endpoint
Number and p
in the mean 
number of migraine days per month on treatment by migraine severity in each month 
and overall in the DBT phase 
Pop. Summary
Frequency by treatment group and difference in percentages between treatment groups 
by migraine severity 
Objective 
 
by migraine severity (total; moderate or severe) in each month and the entire 
course of the DBT phase – Efficacy 
Endpoint 
Number and p
in the mean 
number of migraine days per month on treatment by migraine severity in each month 
and overall in the DBT phase  
Pop. Summary 
Frequency by treatment group and difference in percentages between treatment groups 
by migraine severity 
Objective 
LFT elevations – Safety 
Endpoint 
Number and percentage of subjects with LFT elevations (ALT, AST, or TBL) on 
treatment in DBT and OLE phases 
Pop. Summary 
Frequency by treatment group and overall 
Objective 
LFT elevations > 3 x ULN in temporal association with AEs – Safety 
Endpoint 
Number and percentage of subjects with ALT or AST elevations > 3 x ULN 
concurrent with nausea, vomiting, anorexia, abdominal pain, or fatigue on treatment in 
DBT and OLE phases 
Pop. Summary 
Frequency by treatment group and overall 
Objective 
MSQoL – Outcomes Research 
Variable 
Change from baseline in the MSQoL score over time for each domain in the DBT and 
OLE phases 
Pop. Summary
Change in MSQoL score from baseline at each visit and last visit for each domain by 
treatment group and overall using descriptive statistics 
Objective 
PoM – Outcomes Research 
Variable 
Number and percentage of subjects in each of 5 preference categories of study 
medication relative to previous migraine medications over time 
Pop. Summary
Frequency by treatment group  and overall at each visit and last visit 


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Objective 
SM – Outcomes Research 
Variable 
Number and percentage of 
satisfied to completely dissatisfied) of study medication over time 
Pop. Summary
Frequency by treatment group and overall at each visit and last visit 
Objective 
MIDAS – Outcomes Research 
Variable 
Change from baseline in MIDAS scores over time 
Pop. Summary
Change in total, absenteeism, presenteeism, and item scores from baseline at each visit 
and last visit by treatment group and overall using descriptive statistics 
Objective 
CGI-c – Outcomes Research   
Variable 
Number and p
improvement categories (very 
much improved to very much worse) relative to OP over time 
Pop. Summary
Frequency of subjects at each visit and last visit by treatment group and overall 
Objective
Reduction in the mean number of migraine days per week by migraine severity 
(total; moderate or severe) in the first week of the DBT phase – Efficacy 
Endpoint 
Change from OP in the mean number of migraine days per week on treatment by 
migraine severity in the first week of the DBT phase  
Pop. Summary
Change from OP by treatment group using descriptive statistics and model, and 
difference between treatment groups from model by migraine severity 
Objective 
Frequency of use of rescue medication days per month in each month and the 
entire course of the DBT phase – Efficacy 
Endpoint 
Mean number of rescue medication days per month on treatment in each month and 
overall in the DBT phase 
Pop. Summary 
Value by treatment group using descriptive statistics and model, and difference 
between treatment groups from model 
3 POPULATION SAMPLES FOR ANALYSES
The following population samples for analyses (“analysis sets”) will be evaluated and used for 
presentation and analysis of data: 
 Enrolled subjects: Subjects who sign an informed consent form and are assigned a subject 
identification number by IWRS, i.e., non-missing informed consent date. 
 Randomized subjects: Enrolled subjects who are assigned a randomized treatment group 
and prophylactic medication use stratum by IWRS, i.e., non-missing IWRS randomization 
date. 
 Modified intent-to-treat (mITT) subjects: Enrolled subjects who were randomized only 
once and received at least one dose of double-blind (DB) study medication (rimegepant or 


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placebo), i.e., non-missing DBT start date. This corresponds to the Full Analysis Set in the 
BHV3000-305 Protocol. 
o Evaluable mITT subjects: mITT subjects with  14 days of eDiary efficacy data (not 
necessarily consecutive) in both the OP and at least one month (i.e., 4-week interval) in 
the DBT phase. This corresponds to the Efficacy Analysis Set in the BHV3000-305 
Protocol. 
o Evaluable first week mITT subjects: mITT subjects with at least one day of eDiary 
efficacy data in both the OP and the first week of the DBT phase.  
o Menstrual migraine evaluable mITT menstruating female subjects: mITT 
menstruating female subjects with  1 day of eDiary menstrually-related (MR) efficacy 
data and  14 days of eDiary efficacy data (not necessarily consecutive) in both the OP 
and at least one month (i.e., 4-week interval) in the DBT phase.  
o OL rimegepant mITT subjects: mITT subjects who received at least one dose of OL 
rimegepant, i.e., non-missing OL rimegepant start date. 
 Evaluable OL rimegepant mITT subjects: OL rimegepant mITT subjects with  14 
days of eDiary efficacy data (not necessarily consecutive) in both the OP and at least 
one month (i.e., 4-week interval) in the OLE phase. 
 Menstrual migraine evaluable OL rimegepant mITT menstruating female 
subjects: OL rimegepant mITT menstruating female subjects with  1 day of eDiary 
MR efficacy data and  14 days of eDiary efficacy data (not necessarily 
consecutive)in both the OP and at least one month (i.e., 4-week interval) in the OLE 
phase. 
 Treated subjects: Enrolled subjects who received at least one dose of study drug (DB or 
OL), i.e., non-missing study drug start date. This corresponds to the Safety Analysis Set in 
the BHV3000-305 Protocol. 
 OL rimegepant treated subjects: Enrolled subjects who received at least one dose of OL 
rimegepant, i.e., non-missing OL rimegepant start date.  
o Interim subjects: OL rimegepant treated subjects with OL rimegepant start date – 
 
 DB or OL rimegepant treated subjects: Enrolled subjects who received at least one dose of 
rimegepant (DB or OL) i.e., non-missing DB or OL rimegepant start date. This corresponds 
to the Rimegepant Safety Analysis Set in the BHV3000-305 Protocol. 
 Follow-up subjects: Treated subjects whose last contact date is in the follow-up safety 
analysis period. 
 Coronavirus Disease 2019 (COVID-19) impacted: Enrolled subjects who are impacted by 
COVID-19 (see Section 9.1.2). 
See Sections 
 and 
 for derived dates and analysis periods, respectively. 


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4 SCHEDULE OF ANALYSES 
The following planned analyses will be conducted: 
 
Blinded interim analysis for the 90-Day Safety Update with a scheduled database 
snapshot date of 13-June-2019. Analyses will focus on key safety endpoints (e.g., deaths, 
AEs by severity, SAEs, AEs leading to study drug discontinuation, worst laboratory test 
abnormalities, LFT elevations) and supportive endpoints (e.g., subject disposition, 
demographics and baseline characteristics, study drug exposure). 
 
Week 12 unblinded analysis for the CSR when the last treated subject completes the last 
visit in the DBT phase. All analyses described in this SAP will be performed.  
 
Final unblinded analysis for the Addendum Report when the last treated subject 
completes the last visit in the follow-up phase. Analyses will focus on efficacy during the 
OLE phase, and safety during the DB or OL rimegepant phase and follow-up phase. 
Additional unplanned analyses may be performed based on regulatory agency requests. 
5 SAMPLE SIZE AND POWER 
With a sample size of roughly 800 subjects randomized, and 400 subjects per treatment group, 
evaluable mITT population (i.e., 
Efficacy Analysis Set in the BHV3000-305 Protocol). Assuming rimegepant provides roughly a 
1-day advantage over placebo on the primary endpoint and a common standard deviation (SD) of 
s 
for the change in migraine days per month and the SD are consistent with publicly available 
information from another investigational oral calcitonin gene-related peptide (CGRP) antagonist 
for this indication. 
6 STATISTICAL METHODS 
6.1 
General Methods 
Refer to the BHV3000 Core SAP for descriptive statistics, counting rules, rounding rules, 
dictionaries for coding AEs, medical history, and non-study medications, handling duplicate 
subjects, and examples of complete dates. 
Tables will present results by treatment group (i.e., rimegepant and placebo) and overall with the 
following exceptions: 
 
Results for enrolled subjects will be presented only by overall without treatment group. 
 
Exposure, efficacy, and safety results for the DBT phase will be presented only by 
treatment group without overall.
 
Results for follow-up subjects will be presented by 6 groups: rimegepant, placebo, 
placebo to open-label rimegepant, placebo no open-label rimegepant, double-blind or 
open-label rimegepant, and overall. “Placebo to open-label rimegepant” denotes as-
treated placebo subjects who received open-label rimegepant, and “placebo no open-label 


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rimegepant” denotes as-treated placebo subjects who never received open-label 
rimegepant; note that these 2 groups add to the “placebo” group. Also note that the 
“rimegepant” and “placebo to open-label rimegepant” groups add to the “double-blind or 
open-label rimegepant” group. 
The population samples of treated subjects, OL rimegepant treated subjects, DB or OL 
rimegepant treated subjects, interim subjects, and follow-up subjects will be assessed by as-
treated treatment group, i.e., by the treatment actually received, unless specified otherwise. 
Otherwise, all other population samples will be assessed by as-randomized treatment group. 
All listings except administrative listings will identify subjects who are impacted by COVID-19 
(see Section 9.1.2). 
Select listings of measurements over time will display COVID-19 visit impact code for visits that 
are impacted by COVID-19 (see Section 9.1.5.2). 
All statistical analyses will be performed using SAS statistical software (Version 9.4 or higher).   
6.1.1 
Missing Data 
All analyses will be based on observed data unless specified otherwise. A sensitivity analysis of 
the primary endpoint will impute missing data (see Section 6.3.1.1). 
6.1.2 
Type 1 Error Control 
Type 1 error is controlled through the use of hierarchical testing. The significance of the primary 
endpoint is evaluated at the 0.05 level. If the primary endpoint is significant, then the following 
secondary endpoints will be tested hierarchically in the following order, each at the 0.05 level:  
1. Proportion of subjects with  
reduction from OP in the mean number of moderate or 
severe migraine days per month in the last month of the DBT phase 
2. Change from OP in the mean number of migraine days per month in the entire DBT phase 
3. Mean number of rescue medications days per month in the last month of the DBT phase 
4. Change from OP in the mean number of migraine days per month in the first month of the 
DBT phase 
5. Change from baseline in MSQoL restrictive role function score at Week 12 of the DBT phase 
6. Change from baseline in MIDAS total score at Week 12 of the DBT phase. 
Thus, a secondary endpoint will be tested only if the preceding secondary endpoint in the 
hierarchy is determined to be significant. Descriptive p-values will be provided for any non-
significant secondary endpoints and comparative exploratory endpoints.  


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6.1.3 
Subgroups 
Efficacy subgroup tables will present results by subgroup level for subjects with non-missing 
subgroup level data, unless specified otherwise. Safety subgroup tables will present results by 
subgroup level and overall analogously.  
Subgroup levels may be redefined or combined based on the availability of data. 
6.1.3.1 
Efficacy Subgroups for Evaluable mITT Subjects 
For evaluable mITT subjects, the following efficacy subgroups are of interest: 
 
Age: < 40,  40, < 65 ,  65 
 
Sex: female, male 
 
Race: White, Black or African American, Other Including Asian, Asian 
 
Ethnicity: Hispanic or Latino, Not Hispanic or Latino 
 
Baseline body mass index (BMI; kg/m2): < 25,  25 to < 30,  30  
 
Historical number of moderate or severe migraine attacks per month: < 6,  6, < 8,  8, < 
12,  12, < 15,  15 
Historical primary migraine type: migraine with aura, migraine without aura 
Historical chronic migraine: yes, no
 
Prophylactic migraine medication use at randomization (i.e., IWRS randomization strata): 
yes, no 
 
Total migraine days per month in the OP: < 14,  14. 
6.1.3.2 
Safety Subgroups for Treated Subjects 
For treated subjects, the following safety subgroups are of interest: 
Age: < 40,  40, < 65 ,  65 
 
Sex: female, male 
 
Sex and age: female < 40, female  40, male < 40, male  40 
Race: White, Black or African American, Other Including Asian, Asian 
Ethnicity: Hispanic or Latino, Not Hispanic or Latino 
 
Baseline body mass index (BMI; kg/m2): < 25,  25 to < 30,  30  
Prophylactic migraine medication use at randomization: yes, no.


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6.1.3.3 
Safety Subgroups for DB or OL Rimegepant Treated Subjects 
For DB or OL rimegepant treated subjects, the following safety subgroups are of interest: 
 
Time on DB or OL rimegepant: < 6 months,  6 months,  1 year (see Section 6.2.6.1). 
These apply to the Addendum Report. 
6.1.3.4 
Safety Subgroups for OL Rimegepant Treated Subjects 
For OL rimegepant treated subjects, the following safety subgroups are of interest: 
 
Average OL rimegepant exposure (tablets per month):  14, > 14 to  16, > 16 (see 
Section 6.2.6.1). 
6.2 
Study Population 
6.2.1 
Population Samples for Analyses 
The number of subjects in each population sample listed in Section 3 will be presented by as-
randomized or as-treated treatment group (see Section 6.1), not randomized, and overall.  
Inclusion and exclusion from the evaluable mITT sample population will be summarized by as-
randomized treatment group and overall for randomized subjects. Reasons for exclusion 
categories are mutually exclusive and will include the following: (1) not mITT: not treated with 
DBT; (2) not mITT: treated with DBT but randomized more than once; (3) mITT but not 
evaluable: < 14 days of efficacy data in OP only; (4) mITT but not evaluable: < 14 days of 
efficacy data in all 3 months of the DBT phase only; (5) mITT but not evaluable: < 14 days of 
efficacy data in both OP and in all 3 months of the DBT phase. See Section 6.3.1.1 for months. 
A by-subject listing of population samples for analyses will be provided for enrolled subjects. 
The listing will flag subjects in populations, and include as-treated treatment group. 
6.2.2 
Enrollment 
Enrollment by (1) country and site and (2) age group will be tabulated for enrolled subjects. The 
enrollment by country and site table also displays results for randomized subjects and treated 
subjects. Refer to the BHV3000 Core SAP for additional details.  
A frequency table of accrual by randomization year and month will also be provided for 
randomized subjects. 
6.2.3 
Subject Disposition 
By-subject listings of subject disposition in the DBT, OLE, and follow-up phases will be 
provided respectively for enrolled subjects, OL rimegepant treated subjects, and follow-up 
subjects. Listings for the OLE and follow-up phases will identify subjects who terminated the 
phase prematurely due to COVID-19 (see Section 9.1.4). 
Another by-subject listing of eligibility with inclusion and exclusion criteria will be provided for 
enrolled subjects. 


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6.2.3.1 
Subject Disposition From Enrollment to Randomization
Subject disposition from enrollment to randomization will be summarized for enrolled subjects 
overall as the number and percentage of subjects in the following categories: 
 Randomized 
 Not randomized 
 Reasons for discontinuation, including not reported (based on the DB Subject Status Case 
Report Form [CRF]). 
6.2.3.2 
Subject Disposition From Randomization to Treatment 
Subject disposition from randomization to treatment will be summarized for randomized subjects 
by as-randomized treatment group and overall as the number and percentage of subjects in the 
following categories: 
 Treated 
 Not treated 
 Reasons for discontinuation, including not reported (based on the DB Subject Status CRF). 
6.2.3.3 
Subject Disposition in the DBT Phase 
Subject disposition in the DBT phase will be summarized for treated subjects by as-treated 
treatment group and overall as the number and percentage of subjects in the following categories: 
 
Ongoing in DBT phase (identified as subjects with missing response to the question about 
completing all DB visits on the DB Subject Status CRF) 
 
Completed DBT phase (identified as subjects with primary completion/discontinuation 
reason of “Completed Double Blind Phase” on the DB Subject Status CRF) 
 
Did not complete DBT phase (identified as subjects with “no” response to the question 
about completing all DB visits or primary completion/discontinuation reason not missing 
but not equal to “Completed Double Blind Phase” on the DB Subject Status CRF) 
o Reasons for not completing, including not reported 
 
Continuing to OLE phase (identified as subjects with “yes” response to the question about 
continuing to OL on the DB Subject Status CRF) 
 
Continuing to follow-up phase (identified as subjects with “yes” response to the question 
about continuing to follow-up on the DB Subject Status CRF) 
 
Not continuing to follow-up phase (identified as subjects with “no” response to the question 
about continuing to follow-up on the DB Subject Status CRF) 
o Reasons for not continuing, including not reported 


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Completed DBT phase but not continuing to OLE phase (identified as subjects with 
primary completion/discontinuation reason of “Completed Double Blind Phase” and “no” 
response to the question about not continuing to OL on the DB Subject Status CRF) 
o Reasons for not continuing, including not reported. 
Subject disposition in the DBT phase will be summarized analogously for evaluable mITT 
subjects by as-randomized treatment group and overall only. 
Subject disposition in the DBT phase will be summarized analogously for treated subjects by 
subgroup level and overall for all safety subgroups of interest described in Section 6.1.3.2 for 
each treatment group. 
6.2.3.4 
Subject Disposition in the OLE Phase 
Subject disposition in the OLE phase will be summarized for OL rimegepant treated subjects by 
as-treated treatment group and overall as the number and percentage of subjects in the following 
categories: 
 
Ongoing in OLE phase (identified as subjects with missing response to the question about 
completing all OL visits on the OL Subject Status CRF) 
 
Completed OLE phase (identified as subjects with primary completion/discontinuation 
reason of “Completed Open Label Phase” on the OL Subject Status CRF)
 
Did not complete OLE phase (identified as subjects with “no” response to the question 
about completing all OL visits or primary completion/discontinuation reason not missing 
but not equal to “Completed Open Label Phase” on the OL Subject Status CRF) 
o Reasons for not completing, including not reported 
 
Terminated OLE phase prematurely due to COVID-19 (see Section 9.1.4) 
o Reasons for termination, including not reported  
 
Continuing to follow-up phase (identified as subjects with “yes” response to the question 
about continuing to follow-up on the OL Subject Status CRF) 
 
Not continuing to follow-up phase (identified as subjects with “no” response to the question 
about continuing to follow-up on the OL Subject Status CRF) 
o Reasons for not continuing, including not reported. 
Subject disposition in the OLE phase will be summarized analogously for OL rimegepant mITT 
subjects by as-randomized treatment group and overall. 
Subject disposition in the OLE phase will also be summarized analogously for OL rimegepant 
treated subjects by subgroup level and overall for all safety subgroups of interest described in 
Section 6.1.3.4. 


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6.2.3.5 
Subject Disposition in the Follow-up Phase 
Subject disposition in follow-up phase will be summarized for follow-up subjects by as-treated 
treatment group and overall as the number and percentage of subjects in the following categories: 
 
Did not formally enter the follow-up phase (identified as subjects with missing response to 
the question about completing all follow-up visits on the Follow-up Subject Status CRF and 
without “yes” response to the question about continuing to follow-up on the DB or OL 
Subject Status CRF) 
 
Ongoing in follow-up phase (identified as subjects with missing response to the question 
about completing all follow-up visits on the Follow-up Subject Status CRF and with “yes” 
response to the question about continuing to follow-up on the DB or OL Subject Status 
CRF) 
 
Completed follow-up phase (identified as subjects with “yes” response to the question about 
completing all follow-up visits on the Follow-up Subject Status CRF) 
 
Did not complete follow-up phase (identified as subjects with “no” response to the question 
about completing all follow-up visits on the Follow-up Subject Status CRF) 
o Reasons for not completing, including not reported 
Terminated follow-up phase prematurely due to COVID-19 (see Section 9.1.4) 
o Reasons for termination, including not reported. 
6.2.4 
Protocol Deviations 
A protocol deviation is any variance from the approved protocol, either intentional or 
unintentional.  The possible categories for all protocol deviations are as follows: 
 
Informed Consent 
 
Inclusion/Exclusion Criteria (specify #) 
 
Concomitant Medication 
 
SAE Reporting 
 
Regulatory 
 
Drug Storage/Preparation 
 
Drug Administration 
 
Visit Schedule 
 
EPro Diary Non-compliance 
 
Non-compliance (i.e., trends, missed assessments). 


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A significant protocol deviation is any deviation that could impact subject safety or the integrity 
of the trial. For the purposes of this study, significant protocol deviations will be defined as the 
following: 
 
Inadequate informed consent or initiation of study procedures prior to completing the 
informed consent 
 
Subjects receiving an enrollment date in IWRS, but not meeting the inclusion/exclusion 
criteria 
 
Unreported SAEs 
Use of prohibited medication as defined by the protocol 
eDiary non-compliance 
Repeated deviations of the same nature for a given site or subject. 
The sponsor, or designee, will be responsible for producing the final significant protocol 
deviation file (formatted as a Microsoft Excel file). This file will include site, subject ID, 
deviation date, deviation type, and a description of the protocol deviation. 
The number and percentage of randomized subjects with significant protocol deviations will be 
summarized by deviation type and by as-randomized treatment group and overall. Deviation 
types will be presented in descending order of overall frequency. 
A by-subject listing of significant protocol deviations will be provided for enrolled subjects.   
6.2.5 
Pre-Treatment Characteristics 
Pre-treatment characteristics will include the following: demographics and baseline 
characteristics; medical history; migraine history; and cardiac and other risk factors. 
Pre-treatment characteristics will be summarized descriptively by as-randomized treatment group 
and overall for evaluable mITT subjects to support efficacy. 
Pre-treatment characteristics will also be summarized by as-treated treatment group and overall for 
treated subjects to support safety. 
Demographics and baseline characteristics, as well as migraine history, will also be summarized by as-
randomized treatment group and overall for randomized subjects not in the evaluable mITT population. 
Demographics and baseline characteristics will also be summarized analogously for treated subjects by 
subgroup level and overall for all safety subgroups of interest described in Section 6.1.3.2 for each 
treatment group. 
Demographics and DB or OL rimegepant baseline characteristics (including both age at informed consent 
and age at DB or OL rimegepant baseline), as well as migraine history and cardiac and other risk factors, 
will be summarized by as-treated treatment group and overall for DB or OL rimegepant treated subjects 
to support DB or OL rimegepant safety. Age at DB or OL rimegepant baseline is defined using DB or OL 
rimegepant start date as the reference date (see Section 7.7). These will also be summarized 


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analogously by subgroup level and overall for all safety subgroups of interest described in Section 
6.1.3.3. 
Demographics and OL rimegepant baseline characteristics (including both age at informed consent and 
age at OL rimegepant baseline), as well as migraine history and cardiac and other risk factors, will be 
summarized by subgroup level and overall for all safety subgroups of interest described in Section 
6.1.3.4 for OL rimegepant treated subjects to support OL rimegepant safety. Age at OL rimegepant 
baseline is defined using OL rimegepant start date as the reference date (see Section 7.7). 
Prophylactic migraine medication use at randomization (i.e., IWRS randomization strata) will be 
summarized as categorical parameters for randomized subjects. 
Baseline will be defined according to population as follows: 
 Enrolled subjects not randomized: Last non-missing value 
 Randomized subjects not treated: Last non-missing value on or before the IWRS 
randomization date/time
 mITT subjects and treated subjects: Last non-missing value on or before the study drug start 
date/time (i.e., in the pre-treatment analysis period; see Sections 
 and
) 
 DB or OL rimegepant treated subjects: Last non-missing value on or before the DB or OL 
rimegepant start date (i.e., DB or OL rimegepant baseline) 
 OL rimegepant treated subjects: Last non-missing value on or before the OL rimegepant start 
date (i.e., OL rimegepant baseline). 
The following listings will be provided for enrolled subjects: 
 Demographics, including informed consent date. All reported races will be displayed for 
subjects who reported multiple races. 
 Baseline characteristics, including previous BHV3000-305 subject identifier from the 
Rescreen CRF 
 Medical history, displaying results by SOC and PT 
Migraine history split into general migraine history, migraine symptom history, and migraine 
aura history
Cardiac and other risk factors for subjects with any risk factor present. Only records with 
“yes” responses to questions about having risk factors will be displayed. 
6.2.5.1 
Demographics and Baseline Characteristics 
Refer to the BHV3000 Core SAP for the table of demographics and baseline characteristics. This 
table will also summarize the following parameters: 
Experiences menstrual periods (yes, no; if female)
Screened for previous BHV3000 study (any previous study, BHV3000-111, BHV3000-201, 
BHV3000-301, BHV3000-302, BHV3000-303) 


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 Prophylactic migraine medication use at randomization (yes, no). 
6.2.5.2 
Medical History 
Medical history will be summarized by system organ class (SOC) and preferred term (PT), and 
displayed in descending order of overall frequency within SOC and PT. 
6.2.5.3 
Migraine History
Refer to the BHV3000 Core SAP for the migraine history table. 
6.2.5.4 
Cardiac and Other Risk Factors
Refer to the BHV3000 Core SAP for the table of cardiac and other risk factors.  
6.2.6 
Exposure 
Analyses will be based on as-treated treatment group to support safety, unless specified 
otherwise. 
6.2.6.1 
Study Medication
The eDiary has multiple sources of study drug exposure. Subjects are required to report study 
drug date/times and doses in the following 4 eDiary sources as appropriate: (1) study medication 
from the scheduled dosing report; (2) study medication to treat headache or aura from the 
evening report headache log; (3) additional study medication to treat headache or aura from the 
evening report headache log; or (4) study medication to treat headache or aura from the follow-
up headache log. In addition, sites may report study drug dates and doses in the eDiary 
medication reconciliation form from missed scheduled dosing reports or evening report headache 
logs.  
Imputed OL rimegepant to treat headache date/time will be derived for subjects who answer 
“yes” to the question about having already taken study medication to treat a headache on the 
eDiary scheduled dosing report, but do not have study drug data from any other eDiary source on 
the same day. Subjects with non-missing imputed OL rimegepant to treat headache date/times 
will be credited with taking 1 tablet of OL rimegepant on each of those days to account for 
missed OL rimegepant exposure from eDiary non-compliance. Otherwise, if no study drug data 
were reported in the eDiary on a given day (i.e., missing study drug date/time), then it is assumed 
that the subject did not take study drug that day. See Section 
 for derived dates.  
A by-subject listing will present eDiary exposure (i.e., number of tablets taken) and drug 
accountability for randomized subjects. This listing will include all drug accountability data 
including treatment (DB rimegepant; DB placebo; OL rimegepant) corresponding to the kit ID, 
but only eDiary records with non-missing study drug start date/time and number of tablets > 0. 
The eDiary subcategory of question (scheduled dosing report; evening report headache log 
[study medication; additional study medication]; follow-up headache log; and medication 
reconciliation form) will also be displayed. COVID-19 visit impact code for visits impacted by 
COVID-19 will also be displayed (see Section 9.1.5.2). 


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Another by-subject listing will present eDiary exposure (i.e., total number of tablets taken) in 
each month (i.e., 4-week interval) in the DBT and OLE phases for treated subjects. This will also 
display cumulative DBT, OL rimegepant, and DB or OL rimegepant exposures from both 
sources (i.e., eDiary and drug accountability), and flag subjects with 10 cumulative tablet 
difference between the 2 sources. 
A by-subject administrative listing of batch numbers sorted by batch number and site-subject ID 
will be provided for treated subjects.
eDiary Rimegepant or Placebo Exposure During Double-Blind Treatment 
eDiary rimegepant or placebo exposure during the DBT phase will be summarized descriptively 
by treatment group for treated subjects, and will include the following parameters: 
 Time on DBT (weeks), derived as (DBT end date – DBT 
 
 Cumulative DB exposure (tablets), derived by summing number of tablets across DB study 
drug records 
 Average DB exposure (tablets per month), derived as 4 × cumulative DB exposure/time on 
DBT 
 Total DB exposure (tablets) summed across all subjects, derived by summing cumulative DB 
exposure across all subjects 
 Total DB exposure (patient-years), derived by summing (DBT end date – DBT start date + 
1)/365.25 across all subjects. 
 Number and percentage of subjects in the following average DB exposure (tablets per month) 
categories: 
 > 16.8 
above EOD dosing) 
 > 15.4 
above EOD dosing) 
 
 12.6 to  15.4 (  1
of EOD dosing) 
 
 11.2 to  16.8 (  
EOD dosing) 
 
 12.6 (  
 
 
 11.2 (  
 
 Number and percentage of subjects who took > 1 DB tablet on any 1 day. This could be from 
the same bottle or different bottles due to an unscheduled visit or erroneous eDiary usage. 
 Single study drug record (i.e.,  2 tablets taken from a single source) 
 Multiple study drug records (i.e.,  2 tablets taken based on multiple sources with the 
same study drug date) 


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Subject-reported duplicate data (i.e., duplicate study drug times from  2 eDiary 
subject-reported sources)
 
Subject-reported non-duplicate data (i.e., non-duplicate study drug times from  2 
eDiary subject-reported sources) 
 
Both site-reported data on medication reconciliation form and subject-reported data 
(i.e., duplicate study drug dates from the medication reconciliation form and an 
eDiary subject-reported source) 
 
Site-reported data on medication reconciliation form only (i.e., duplicate study drug 
dates only from the medication reconciliation form) 
 Number and percentage of subjects who took: 
 
 12 DB tablets per month for 3 consecutive months, i.e., 3 consecutive 4-week intervals 
(see first paragraph below)
 
 13 ,  14,  15, and  16 DB tablets per month for 3 consecutive months 
 Number and percentage of subjects who took the incorrect DB study drug: 
 All the time (i.e., as-treated treatment group not equal to as-randomized treatment group) 
 At least once (i.e., subject randomized to rimegepant who took placebo; subject 
randomized to placebo who took rimegepant). 
eDiary rimegepant or placebo exposure during DBT will also be summarized descriptively by 
subgroup level and overall for all safety subgroups of interest described in Section 6.1.3.2 for 
each treatment group. 
eDiary tablets per month will assess the number of 4-week (28-day) intervals in which a subject 
exceeded select tablet counts from the DBT start date to the DBT end date, where the number of 
4-week intervals are consecutive (see Section 6.3.1.1 for months). For example, suppose a 
subject takes 20 tablets through 4 weeks, 10 tablets after 4 weeks to 8 weeks, and 25 tablets after 
8 weeks to 12 weeks. Thus, this subject is not considered to have taken  14 tablets (more than 
EOD frequency) per month for 3 consecutive months.  
See Section 
 for the definition of study days used to define analysis visit windows. 
In order to determine subjects who took incorrect DB study drug, eDiary DB study drug dates 
will be compared to sorted kit dispense dates recorded on the Drug Accountability CRF.  Study 
drug will be considered to be taken from a kit if the kit dispense date  study drug date < next kit 
dispense date; if > 1 kit ID has the same dispense date, then study drug will be considered to be 
taken from the kit with the smallest kit ID. Kit IDs from drug accountability will then be 
compared to kit IDs in the unblinded container file to determine whether the kit contained DB 
rimegepant, DB placebo, or OL rimegepant. 
A Kaplan-Meier mortality table will summarize time to DBT discontinuation in 4-week intervals 
(i.e.,  4, > 4 to  8, > 8 to  12, > 12) by treatment group and overall for treated subjects. A 


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Kaplan-Meier mortality plot by treatment group will display the percentage of treated subjects on 
DBT (y-axis) versus weeks (x-axis). Time to DBT discontinuation (weeks) is defined as (DBT 
end date – DBT 
. Subjects will be considered to have discontinued DBT if they 
have non-missing DBT last date. Otherwise, in an interim analysis or snapshot before the Week 
12 interim analysis database lock, subjects will be censored at the DBT end date. 
eDiary DB or OL Rimegepant Exposure During the Entire Study 
eDiary DB or OL rimegepant exposure during the entire study (i.e., both DBT and OLE phases 
combined) will be summarized descriptively by treatment group and overall for DB or OL 
rimegepant treated subjects, and will include the following parameters: 
 Time on DB or OL rimegepant (weeks), derived as (DB or OL rimegepant end date – DB or 
OL rimegepant 
 
 Number and percentage of subjects in the following time on DB or OL rimegepant (weeks) 
categories:  11, < 23,  23,  51, 63. These correspond to using a 1-week lower bound on 
3, 6, 12, and 15 months, respectively. 
 Cumulative DB or OL rimegepant exposure (tablets), derived by summing number of DB or 
OL rimegepant tablets across records with non-missing DB or OL rimegepant date/times.  
 Average DB or OL rimegepant exposure (tablets per month), derived as 4 × cumulative DB 
or OL rimegepant exposure/time on DB or OL rimegepant 
 Total DB or OL rimegepant exposure (tablets) summed across all subjects, derived by 
summing cumulative DB or OL rimegepant exposure across all subjects 
 Number and percentage of subjects who took > 1 DB or OL rimegepant tablet on any 1 day 
 Single study drug record 
 Multiple study drug records 
 
Subject-reported duplicate data  
 
Subject-reported non-duplicate data 
 
Both site-reported data on medication reconciliation form and subject-reported data  
 
Site-reported data on medication reconciliation form only 
Note that imputed OL rimegepant to treat headache date/time by definition will not 
contribute to taking more than 1 OL rimegepant tablet per day. 
 Total DB or OL rimegepant exposure (patient-years), derived by summing (DB or OL 
rimegepant end date – DB or OL rimegepant start date + 1)/365.25 across all subjects. 
eDiary DB or OL rimegepant exposure during the entire study will also be summarized 
descriptively by subgroup level and overall for all safety subgroups of interest described in 
Section 6.1.3.3. 


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A Kaplan-Meier mortality table will summarize time to rimegepant discontinuation in 4-week 
intervals (i.e.,  4, > 4 to  8, etc.) by treatment group and overall for DB or OL rimegepant 
treated subjects. A Kaplan-Meier mortality plot (overall, not by treatment group) will display the 
percentage of DB or OL rimegepant treated subjects on rimegepant (y-axis) versus weeks (x-
axis). Time to DB or OL rimegepant discontinuation (weeks) is defined as (DB or OL 
rimegepant end date – DB or OL rimegepant 
. Subjects will be considered to 
have discontinued DB or OL rimegepant if they have non-missing DB or OL rimegepant last 
date. Otherwise, in an interim analysis, subjects will be censored at the DB or OL rimegepant 
end date. 
 
eDiary Study Drug Exposure 
eDiary study drug exposure will be summarized descriptively by treatment group and overall for 
treated subjects, and will include the following parameters: 
 Time in the OP (weeks) 
 Time from randomization to last contact (weeks), where study drug start date will be used if 
IWRS randomization date is missing 
 Time on DBT (weeks) 
 Cumulative DB exposure (tablets) 
 Average DB exposure (tablets per month) 
 Total DB exposure (tablets) summed across all subjects 
 Time on OL rimegepant (weeks) 
 Cumulative OL rimegepant exposure (tablets) 
 Average OL rimegepant exposure (tablets per month) 
 Total OL rimegepant exposure (tablets) summed across all subjects 
 Time on study drug (weeks), derived as (study drug end date – study drug 
 
 Number and percentage of subjects in the following time on study drug (weeks) categories:  
11,  23,  51,  63. These correspond to using a 1-week lower bound on 3, 6, 12, and 15 
months, respectively. 
 Cumulative study drug exposure (tablets), derived by summing number of tablets across 
study drug records (DBT + OLE) 
 Average study drug exposure (tablets per month), derived as 4 × cumulative study drug 
exposure/time on study drug 
 Total study drug exposure (tablets) summed across all subjects, derived by summing 
cumulative study drug exposure across all subjects 


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 Total study drug exposure (patient-years), derived by summing (study drug end date – study 
drug start date + 1)/365.25 across all subjects 
 Time in follow-up (weeks), derived as derived as (last contact date – study drug last date)/7, 
for follow-up subjects 
 Time on study (weeks), derived as (last contact date – study drug start date + 1)/7 
 Number and percentage of subjects in the following time on study (weeks) categories:  11, 
 23,  51,  63. These correspond to using a 1-week lower bound on 3, 6, 12, and 15 
months, respectively. 
Kaplan-Meier mortality tables will summarize time to study drug discontinuation and time to 
study discontinuation in 4-week intervals (i.e.,  4, > 4 to  8, etc.) by treatment group and 
overall for treated subjects. A Kaplan-Meier mortality plot by treatment group will display the 
percentage of treated subjects on study drug (y-axis) versus weeks (x-axis).  
 Time to study drug discontinuation (weeks) is defined as (study drug end date – study drug 
start date + 1)/7. Subjects will be considered to have discontinued study drug if they have 
non-missing study drug last date/time. Otherwise, in an interim analysis or snapshot before 
the final database lock, subjects will be censored at the study drug end date. 
 Time to study discontinuation (weeks) is defined as (last contact date – IWRS randomization 
date + 1)/7.  If a subject is not randomized, then the study drug start date will be used instead 
of IWRS randomization date. In an interim analysis or snapshot before the final database 
lock, subjects will be considered to have discontinued the study if any of the following 
criteria 1 through 4 are met: 
1) All of the following criteria from the DB Subject Status CRF are met (see 
Section 6.2.3.3): 
a) Completed or did not complete the DB phase 
b) Not continuing to OLE phase 
c) Not continuing to follow-up phase 
2) All of the following criteria from the OL Subject Status CRF are met (see 
Section 6.2.3.4) 
a) Completed or did not complete the OLE phase 
b) Not continuing to follow-up phase  
3) Did not formally enter the follow-up phase (see Section 6.2.3.5) 
4) Completed or did not complete the follow-up phase (see Section 6.2.3.5) 
Otherwise, subjects will be censored at the last contact date. At the final database lock, all 
subjects will be considered to have discontinued the study. (This definition of study 
discontinuation was applied to the CSR.) 
 


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eDiary OL Rimegepant Exposure 
eDiary OL rimegepant exposure will be summarized descriptively by subgroup level and overall 
for all safety subgroups of interest described in Section 6.1.3.4, and will include the following 
parameters: 
 Time on OL rimegepant (weeks) 
 Number and percentage of subjects in the following time on OL rimegepant (weeks) 
categories:  11,  23,  51. These correspond to using a 1-week lower bound on 3, 6, and 12 
months, respectively. 
Cumulative OL rimegepant exposure (tablets)
 Average OL rimegepant exposure (tablets per month) 
 Number and percentage of subjects in the subgroup categories defined in Section 6.1.3.4 
 Number and percentage of subjects who took > 1 OL rimegepant tablet on any 1 day 
o
Single study drug record
o
Multiple study drug records
 Subject-reported duplicate data  
 Subject-reported non-duplicate data 
 Both site-reported data on medication reconciliation form and subject-reported data  
 Site-reported data on medication reconciliation form only 
 Total OL rimegepant exposure (tablets) summed across all subjects 
 Total OL rimegepant exposure (patient-years), derived by summing (OL rimegepant end date 
– OL rimegepant start date + 1)/365.25 across all subjects. 
6.2.6.2 
Drug Accountability 
Drug accountability is provided by the site on the Drug Accountability CRF.  
Drug Accountability Exposure 
Drug accountability exposure will be summarized with descriptive statistics by treatment group 
and overall for treated subjects: 
 Time from first DB kit dispensed to last DB kit returned (weeks), derived as (latest DB kit 
return date – earliest DB kit dispense date + 1)/7. Subjects who were dispensed  1 DB kit 
but never returned any DB kit will be credited with 1 day.  
 Cumulative DB exposure (tablets) based on DB kits dispensed and returned, derived as 
summing (30 – number of tablets remaining) across records with non-missing DB kit 
dispense and return dates.  
 Average DB exposure (tablets per month) based on DB kits dispensed and returned, derived 


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as 4 × cumulative DB exposure based on DB kits dispensed and returned/time from first DB 
kit dispensed to last DB kit returned.
 Time from first OL kit dispensed to last OL kit returned (weeks), derived as (latest OL kit 
return date – earliest OL kit dispense date + 1)/7. Subjects who were dispensed  1 OL kit 
but never returned any OL kit will be credited with 1 day.  
Cumulative OL exposure (tablets) based on OL kits dispensed and returned, derived as 
summing (30 – number of tablets remaining) across records with non-missing OL kit 
dispense and return dates.  
Average OL exposure (tablets per month) based on OL kits dispensed and returned, derived 
as 4 × cumulative OL exposure based on OL kits dispensed and returned/time from first OL
kit dispensed to last OL kit returned.  
 Time from first DB or OL rimegepant kit dispensed to last DB or OL rimegepant kit returned 
(weeks). This is time from first DB kit dispensed to last DB kit returned for subjects whose 
as-treated treatment group is rimegepant. This is time from first OL kit dispensed to last OL 
kit returned for subjects whose as-treated treatment group is placebo. 
 Cumulative DB or OL rimegepant exposure (tablets) based on DB or OL rimegepant kits 
dispensed and returned. This is cumulative DB and OL combined exposure for subjects 
whose as-treated treatment group is rimegepant, and cumulative OL exposure for subjects 
whose as-treated treatment group is placebo. 
 Average DB or OL rimegepant exposure (tablets per month) based on DB or OL rimegepant 
kits dispensed and returned, derived as 4 × cumulative DB or OL rimegepant exposure based 
on DB or OL rimegepant kits dispensed and returned/time from first DB or OL rimegepant 
kit dispensed to last DB or OL rimegepant kit returned. 
eDiary versus drug accountability cumulative exposure will be summarized by treatment group 
and overall with the number and percentage of subjects in the following categories: 
 
 10,  20,  30 absolute tablet difference in cumulative DB exposure for treated subjects
 
 10,  20,  30,  40,  50 absolute tablet difference in OL rimegepant exposure for OL 
rimegepant treated subjects. 
Absolute tablet difference is defined as the absolute value of {eDiary cumulative exposure 
(tablets) – drug accountability cumulative exposure (tablets)}. 
Drug Accountability Compliance 
Drug accountability compliance will be summarized by as-randomized treatment group and 
overall with the number and percentage of randomized subjects in the following categories: 
 Any kit dispensed 
 Did not return  1 kit dispensed and discontinued study drug, defined as any of the 
following:  
o Randomized subjects who were not treated and did not return  1 DB kit dispensed 


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o Treated subjects who did not return  1 DB kit dispensed and discontinued DBT (i.e., 
non-missing DBT last date)
o OL rimegepant treated subjects who did not return  1 OL rimegepant kit dispensed and 
discontinued OL rimegepant (i.e., non-missing OL rimegepant last date). 
 Did not return any kit dispensed and discontinued study drug. 
Kit dispensed and kit returned will be identified from “yes” responses to the questions “was this 
kit dispensed” and “was this kit returned”, respectively. 
6.2.6.3 
eDiary Compliance 
eDiary Compliance During Pre-Randomization and in the DBT Phase 
eDiary compliance in the OP and DBT phase will be summarized descriptively by treatment 
group and overall for treated subjects for each source (subject; subject or site). Subject sources 
are the scheduled dosing report, evening report headache log, follow-up headache log, PoM, and 
SM survey. Site source is the medication reconciliation form. 
Finding days are those with complete finding dates from any subcategory of question. 
Compliance will be derived for the following periods: 
 Last 28 days before randomization: 100 × (total number of finding days in the last 28 days 
before the IWRS randomization date)/28
 Randomization to last DBT visit: 100 × (total number of finding days from the IWRS 
randomization date to the last DBT visit date)/(total number of days from the IWRS 
randomization date to the last DBT visit date).  
DBT start date will be used if IWRS randomization date is missing. 
For each source and period, eDiary compliance will be summarized as a continuous parameter 
and as the number and percentage of subjects with   80% and  90% compliance.   
eDiary Compliance in the DB or OL Rimegepant Phase 
eDiary compliance in the DB or OL rimegepant phase will be summarized analogously to eDiary 
compliance by treatment group and overall for DB or OL rimegepant treated subjects. 
Compliance will be derived for the following period: 
 DB or OL rimegepant start to last DB or OL rimegepant visit: 100 × (total number of finding 
days from the DB or OL rimegepant start date to the last DB or OL rimegepant visit 
date)/total number of days from the DB or OL rimegepant start date to the last DB or OL 
rimegepant visit date). 


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6.2.6.4 
Non-Study Medications 
Non-study medications will be summarized by therapeutic class and preferred name. For each 
subject, multiple records of the same medication will be counted only once within each 
therapeutic class and preferred name. Medications will be displayed in descending order of 
overall frequency within therapeutic class and preferred name, unless specified otherwise. 
Non-study medications will be identified from the Concomitant Medication and Migraine 
Standard of Care Medications CRFs.  
Migraine standard of care medications are defined as those reported on either the (1) Migraine 
Standard of Care Medications CRF, or (2) Concomitant Medication CRF with medical history, 
AE, additional AE, or other indication indicative of migraine.  
Prophylactic migraine standard of care medications are defined as migraine standard of care 
medications with a “yes” response to the question about prophylactic migraine medication on the 
Migraine Standard of Care Medications CRF. Otherwise, all other migraine standard of care 
medications will be considered to be non-prophylactic. 
See Section 7.6.3 for the definitions of non-study medication types, e.g., prior, current, DBT 
concomitant, DB or OL rimegepant concomitant, follow-up. 
By-subject listings of non-study medications and standard of care migraine medications will be 
provided by therapeutic class and preferred name for enrolled subjects, and will display COVID-
19 visit impact code for visits impacted by COVID-19 (see Section 9.1.5.2). Prophylactic and 
non-prophylactic migraine standard of care medications will be identified, as well as medication 
type. 
Refer to the BHV3000 Core SAP for non-study medication start and stop date imputation, and 
listing content. 
Non-Study Medications for Treated Subjects 
Non-study medications will be summarized by therapeutic class and preferred name by treatment 
group and overall for treated subjects and the following medication types and subsets: 
 Prior medications: all; migraine standard of care; prophylactic migraine standard of care 
 Current medications: all; migraine standard of care; prophylactic migraine standard of care
 DBT concomitant medications (excluding overall treatment group): all; migraine standard of 
care; prophylactic migraine standard of care. 
Medications will be displayed in descending order of rimegepant frequency within therapeutic 
class and preferred name.  
Non-study prophylactic migraine standard of care medications will also be summarized 
analogously by treatment group for mITT subjects with prophylactic migraine medication use at 


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randomization. Medications will be displayed in descending order of overall frequency within 
therapeutic class and preferred name. (This was an adhoc analysis for the CSR.) 
Non-Study Medications for DB or OL Rimegepant Treated Subjects 
Non-study DB or OL rimegepant concomitant medications will be summarized analogously by 
treatment group and overall for DB or OL rimegepant treated subjects and the following subsets: 
all; migraine standard of care; prophylactic migraine standard of care. 
Non-study DB or OL rimegepant concomitant medications will also be summarized analogously 
by subgroup level and overall for all safety subgroups of interest described in Section 6.1.3.3. 
Non-Study Medications for OL Rimegepant Treated Subjects 
Non-study OL rimegepant concomitant medications will be summarized analogously by 
subgroup level and overall for all safety subgroups of interest described in Section 6.1.3.4. 
Medication subsets include the following: all; migraine standard of care; prophylactic migraine 
standard of care. 
Non-Study Medications for Follow-up Subjects 
Non-study follow-up medications will be summarized analogously by treatment group and 
overall for follow-up subjects and the following subsets: all; migraine standard of care; 
prophylactic migraine standard of care. 
6.3 
Efficacy 
Efficacy endpoints will be assessed by as-randomized treatment group.  
Randomization is stratified by prophylactic migraine medication use at randomization (i.e., 
IWRS randomization stratum; yes or no).  Hence, treatment group comparisons of continuous 
efficacy endpoints will be adjusted by prophylactic migraine medication use at randomization, 
whereas treatment group comparisons of binary efficacy endpoints will be stratified by 
prophylactic migraine medication use at randomization (except in subgroup analyses). If there 
are sparse data within a stratum, then results may be presented unstratified.  
In treatment comparisons of binary efficacy endpoints, CIs will be based on a normal 
approximation to the binomial distribution using asymptotic standard error (ASE). Otherwise, 
CIs for continuous efficacy endpoints will be based on the normal distribution. All CIs will be 2-
sided.  
Select efficacy listings will display efficacy analysis period (i.e., OP, on-DBT, on-OL 
rimegepant, and follow-up). See Sections 7.4 and 7.5 for the definition of efficacy analysis 
periods and study days. 


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The following general by-subject efficacy listings will be provided:
 Subjects excluded from the efficacy analysis for randomized subjects not in the evaluable 
mITT population sample, including the reason for exclusion (see Section 3). 
 Primary and secondary efficacy endpoints for randomized subjects, including the reason for 
exclusion from the evaluable mITT population sample (see Sections 6.3.1.1 and 6.3.2) 
 Exploratory endpoints for mITT subjects (see Section 6.3.3). 
6.3.1 
Reduction in Migraine Days per Month 
Subjects are instructed to report headache status (yes, no), severity (mild, moderate, severe, 
none), and characteristics (e.g., aura, nausea, vomiting), as well as medication taken to treat 
headache or during aura, in the eDiary evening report headache log or follow-up headache log 
recorded every day in the OP, DBT, and OLE phases. 
Migraine days per month will be assessed as “migraine days per 4 weeks” to correspond with the 
4-week visit schedule. Migraine days per month are based on data from the previous visit to the 
current visit (i.e., 4-week interval), and are prorated to account for missing migraine reports.  
A by-subject listing will present efficacy analysis period and the following from the eDiary 
evening report headache log and follow-up headache log for enrolled subjects who had a “yes” 
response to having a headache or an aura-only event: headache status; aura-only event status, 
headache lasting  30 minutes status; headache start and end dates; headache severity; headache 
pain features present* (i.e., unilateral, pulsating, worsen or avoid activity), headache pain 
characteristics present (i.e., aura, nausea, vomiting, photophobia, phonophobia); medication used 
to treat headache or during aura* (i.e., study medication, additional study medication, triptan, 
ergotamine, other medication). Migraine days, rescue medication days, and MRM days will also 
be identified in the listing. Parameters marked with “*” will be displayed only for subjects with a 
“yes” response to these questions. COVID-19 visit impact code for visits impacted by COVID-
19 will be displayed (see Section 9.1.5.2). 
Another by-subject listing for treated subjects will present the following: number of migraine 
days per month by severity (total; moderate or severe) in the OP efficacy analysis period, overall 
DBT mean, overall OL rimegepant mean, and in each month (i.e., 4-week interval) in the on-
DBT and on-OL rimegepant efficacy analysis periods; number of days of efficacy data in the 
aforementioned intervals, overall DBT mean, and overall OL rimegepant mean; and migraine 
day values, changes and percent changes from OP in the aforementioned intervals, overall DBT 
mean, and overall OL rimegepant mean.  
See Section 7.6.2.2 for the definitions of efficacy data days and migraine days. 
6.3.1.1 
Reduction in Migraine Days per Month in the DBT Phase: Primary Efficacy 
Endpoint 
The number of migraine days per month in the DBT phase will be examined relative to the 
number of migraine days per month in the OP for evaluable mITT subjects, i.e., subjects with  


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14 days of eDiary efficacy data (not necessarily consecutive) in both the OP analysis period and 
 1 month (i.e., 4-week interval) in the on-DBT analysis period.  
Months in the DBT phase are defined as follows: 
Month 1 (  4 weeks; study days 1 to 28) 
 Month 2 (> 4 to  8 weeks; study days 29 to 56) 
Month 3 (> 8 to  12 weeks; study days 57 to 84) 
Analyses will be based on eDiary efficacy dates in the OP and on-DBT efficacy analysis periods. 
The number of migraine days per month will be prorated to 28 days and derived as follows: 
 OP: 28 × (total number of migraine days in the OP analysis period)/(total number of efficacy 
data days in the OP analysis period).  
 Month (i.e., 4-week interval) in the on-DBT efficacy analysis period: 28 × (total number of 
migraine days in the month)/(total number of efficacy data days in the month). Subjects must 
have  14 days of efficacy data (not necessarily consecutive) in the specified month to be 
evaluable. 
 Overall DBT mean: 28 × (total number of migraine days through Month 3 in the on-DBT 
efficacy analysis period)/(total number of efficacy data days through Month 3 in the on-DBT 
efficacy analysis period). 
Missing Efficacy Data 
Missing efficacy data in the OP and DBT phases will be assessed using the number and 
percentage of mITT subjects in the following categories: 
 Evaluable 
 Not evaluable, i.e., < 14 days of efficacy data in the OP and < 14 days of efficacy data in all 
3 months (i.e., 4-week intervals) of the DBT phase 
o < 14 days of efficacy data in the OP  
o < 14 days of efficacy data in any of the following months (i.e., 4-week intervals) of the 
DBT phase: 
 Month 1:  4 weeks 
 Month 2: > 4 to  8 weeks 
 Month 3: > 8 to  12 weeks 
Descriptive Analyses 
Analyses will be based on evaluable mITT subjects.  


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Values and changes (both absolute and percent) from the OP in the number of migraine days per 
month in the DBT phase will be summarized descriptively as continuous parameters (including 
2-sided normal 95% CIs for mean change) by treatment group and migraine severity in each 
month of the DBT phase and overall DBT mean. Migraine severity categories are (1) total (mild, 
moderate, severe, none, or not reported) and (2) moderate or severe.  
Values and changes will also be summarized by subgroup level for all efficacy subgroups of 
interest described in Section 6.1.3.1. 
The following scatter plots will be produced by treatment group: 
 Change from OP in the number of total migraine days per month in the last month of the 
DBT phase (y-axis) versus number of migraine days per month in the OP (x-axis) 
 Percent change from OP in the number of total migraine days per month in the last month of 
the DBT phase (y-axis) versus number of migraine days per month in the OP (x-axis) 
 Change from OP in the number of total migraine days per month in the overall DBT mean 
(y-axis) versus number of migraine days per month in the OP (x-axis) 
 Percent change from OP in the number of total migraine days per month in the overall DBT 
mean (y-axis) versus number of migraine days per month in the OP (x-axis). 
Plots will include a horizontal reference line at 0. The last 2 plots were included as adhoc 
analyses in the CSR. 
In the percent change analyses, subjects must also have  1 migraine day (i.e., absolute not 
prorated to 28 days) of appropriate migraine severity in the OP analysis period to be included. 
Treatment Group Comparisons 
Analyses will be based on evaluable mITT subjects and total migraine severity, unless specified 
otherwise. 
Principal Analysis
The principal analysis of the primary endpoint will use a generalized linear mixed effect model 
with the following variables: change from the OP in number of total migraine days per month as 
the dependent variable; subject as a random effect; number of total migraine days per month in 
the OP as a covariate; treatment group, prophylactic migraine medication use at randomization, 
month (i.e., months 1 to 3 of the DBT phase), and the month-by-treatment group interaction as 
fixed effects. The model will be repeated by prophylactic migraine medication use at 
randomization (yes, no).The following model estimates will be reported: 
 Least-squares mean (LSM) change from OP, SE, and 95% CI by month and randomization 
stratum (yes, no, overall) for each treatment group 
 Difference in LSM changes from OP between treatment groups (rimegepant  placebo), SE, 
95% CI, and p-value by randomization stratum (yes, no) for each month 


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 Difference in LSM changes from OP between treatment groups (rimegepant  placebo), SE, 
95% CI, and p-value for each month. Results in the last month will support the primary 
objective, results in the first month will support the fourth secondary objective, and results in 
the second month will support the first exploratory objective.
Overall LSM change from OP, SE, and 95% CI by randomization stratum (yes, no, overall) 
for each treatment group 
Difference in overall LSM changes from OP between treatment groups (rimegepant 
placebo), SE, 95% CI, and p-value by randomization stratum (yes, no) 
 Difference in overall LSM changes from OP between treatment groups (rimegepant  
placebo), SE, 95% CI, and p-value. Results will support the second secondary objective. 
These analyses will be repeated for moderate or severe migraine severity to support the first 
exploratory objective. All variables in the model will be the same, except (1) change from the OP 
in number of moderate or severe migraine days per month will be the dependent variable, and (2) 
number of moderate or severe migraine days per month in the OP will be the covariate. 
A longitudinal plot will display the LSM change in the number of total migraine days from OP 
per month (y-axis) versus month of the DBT phase (x-axis). Another longitudinal plot will 
display the LSM change in the number of moderate or severe migraine days from OP per month 
(y-axis) versus month of the DBT phase (x-axis). Error bars will denote 95% CIs. 
Sensitivity Analysis 
A sensitivity analysis of the primary endpoint will use the same generalized linear mixed effect 
model as the principal analysis, but with jump to reference (J2R) to impute missing data in 
months 1 to 3 using N = 1000 datasets. The imputation model will use the following variables: 
age, sex, race, prophylactic migraine medication use at randomization, and the number of 
migraine days per month in the OP. Race may be reduced to fewer levels (e.g., white versus non-
white) based on the availability of data. 
Subgroup Analyses
Subgroup analyses of the primary endpoint will use the same generalized linear mixed effect 
model specified for the principal analysis of the primary endpoint, except without prophylactic 
migraine medication use at randomization. The following model estimates will be reported for 
each subgroup level of all efficacy subgroups of interest specified in Section 6.1.3.1, except 
prophylactic migraine medication use at randomization: 
 LSM change from OP, SE, and 95% CI by month for each treatment group 
 Difference in LSM changes from OP between treatment groups (rimegepant  placebo), SE, 
95% CI , and p-value by month 
 Overall LSM change from OP, SE, and 95% CI for each treatment group 
 Difference in overall LSM changes from OP between treatment groups (rimegepant  
placebo), SE, 95% CI, and p-value. 


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6.3.1.2 
Reduction in Migraine Days per Month in the OLE Phase 
The number of migraine days per month in the OLE phase will be examined relative to the 
number of migraine days per month in the OP for evaluable OL rimegepant mITT subjects, i.e., 
mITT subjects with  14 days of eDiary efficacy data (not necessarily consecutive) in both the 
OP analysis period and  1 month (i.e., 4-week interval) in the on-OL rimegepant efficacy 
analysis period. Results will support an exploratory objective.  
Months in the OLE phase will be defined as: 
 Month 1 (> 12 to  16 weeks; study days 85 to 112) 
 Month 2 (> 16 to  20 weeks; study days 113 to 140)  
 Month 3 (> 20 to  24 weeks; study days 141 to 168) 
Month 4 (> 24 to  28 weeks; study days 169 to 196) 
 Month 5 (> 28 to  32 weeks; study days 197 to 224) 
Month 6 (> 32 to  36 weeks; study days 225 to 252) 
 Month 7 (> 36 to  40 weeks; study days 253 to 280) 
 Month 8 (> 40 to  44 weeks; study days 281 to 308) 
 Month 9 (> 44 to  48 weeks; study days 309 to 336) 
 Month 10 (> 48 to  52 weeks; study days 337 to 364) 
 Month 11 (> 52 to  56 weeks; study days 365 to 392) 
 Month 12 (> 56 to  60 weeks; study days 393 to 420) 
 Month 13 (> 60 to  64 weeks; study days 421 to 448). 
Analyses will be based on eDiary efficacy dates in the OP analysis period and on-OL rimegepant 
efficacy analysis period. 
The number of migraine days per month will be prorated to 28 days, and derived as follows: 
 OP: See Section 6.3.1.1. 
 Month (i.e., 4-week interval) in the on-OL rimegepant efficacy analysis period: 28 × (total 
number of migraine days in the month)/(total number of efficacy data days in the month). 
Subjects must have  14 days of efficacy data (not necessarily consecutive) in the specified 
month to be evaluable. 


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 Overall OL rimegepant mean: 28 × (total number of migraine days through Month 13 in the 
on-OL rimegepant efficacy analysis period)/(total number of efficacy data days through 
Month 13 in the on-OL rimegepant efficacy analysis period). 
Missing Efficacy Data 
Missing efficacy data in the OP and OLE phases will be assessed using the number and 
percentage of OL rimegepant mITT subjects by treatment group and overall in the following 
categories: 
 Evaluable 
 Not evaluable, i.e., < 14 days of efficacy data in the OP and all 13 months (i.e., all 13 4-week 
intervals) in the OLE phase 
 < 14 days of efficacy data in the OP  
 < 14 days of efficacy data in any of the following months in the OLE phase: 
 
Months 1 to 3: > 12 to  24 weeks 
 
Months 4 to 6: > 24 to  36 weeks 
 
Months 7 to 9: > 36 to  48 weeks 
 
Months 10 to 13: > 48 to  64 weeks 
Descriptive Analyses 
Analyses are based on evaluable OL rimegepant mITT subjects. 
Values and changes (both absolute and percent) from the OP in the number of migraine days per 
month in the OLE phase will be summarized descriptively as continuous parameters (including 
2-sided normal 95% CIs for mean change) by treatment group (including overall) and severity 
(total; moderate or severe) in each month of the OLE phase and overall OL mean. Results will 
support the exploratory objective about OLE phase efficacy. 
A scatter plot by treatment group will display the change in the number of total migraine days 
per month in the OL overall mean (y-axis) versus number of migraine days per month in the OP 
(x-axis). Another scatter plot by treatment group will display the percent change in the number of 
total migraine days per month in the OL overall mean (y-axis) versus number of migraine days 
per month in the OP (x-axis). Plots will include a horizontal reference line at 0. 
A longitudinal plot will display the mean change from OP in the number of total migraine days 
per month (y-axis) versus month of the OLE phase (x-axis). Another longitudinal plot will 
display the mean change from OP in the number of moderate or severe migraine days per month 
(y-axis) versus month of the OLE phase (x-axis). Error bars will denote 95% CIs. 
In the percent change analyses, subjects must also have  1 migraine day (i.e., absolute not 
prorated to 28 days) of appropriate severity in the OP analysis period to be included. 


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6.3.2 
Secondary Efficacy Endpoints  
6.3.2.1 
Percentages of Subjects with Reduction in Migraine Days per Month 
Analyses will be based on evaluable mITT subjects and evaluable OL rimegepant mITT subjects. 
In analyses by months, subjects must (1) achieve the reduction criterion from OP in the number 
of migraine days in the specified month, (2) be evaluable (i.e., have  14 days of efficacy data 
[not necessarily consecutive
(absolute 
not prorated to 28 days) of appropriate migraine severity in the OP analysis period to be 
classified as responders in the specified month. Otherwise, subjects will be classified as failures 
in the specified month.  
In analyses of the overall DBT or OLE mean, subjects must (1) achieve the reduction criterion 
(absolute not prorated to 28 days) of appropriate migraine severity in the OP analysis period to 
be classified as responders. Otherwise, subjects will be classified as failures. 
Percentages of Subjects With Reduction in Migraine Days per Month in the DBT Phase
Analyses will be based on evaluable mITT subjects with eDiary efficacy dates in the OP and on-
DBT efficacy analysis periods (see Section 6.3.1.1).  
Descriptive Analyses 
The number and percentage of evaluable mITT subjects with reductions from the OP in the 
number of migraine days per month in the DBT phase will be presented by treatment group and 
severity (total; moderate or severe) in each month of the DBT phase and overall DBT mean (see 
Section 6.3.1.1 for months). Reduction from OP categories will be
 5,  0; 
> 0 to  2; > 2 to  4; > 4 to  6; > 6 to  8; > 8 to  10; > 10 to  12; > 12 to  14; > 14
 Analyses by month will be 
presented using the following 2 methods:  
 Non-Evaluable = Failure: Analyses will be based on all evaluable mITT subjects in all 
months. An additional reduction category “Not evaluable” will be included. 
 Non-
migraine severity in the OP analysis period and < 14 days of efficacy data in the specified 
month will be excluded from analyses of the specified month. 
The number and percentages of evaluable mITT subjects with reduction outcomes will be 
presented by treatment group in each month of the DBT phase and overall DBT mean for each 
 75%, and 
. Outcomes categories at each month will be defined as follows: 
 Responder, i.e., 
 14 days of efficacy data in the specified month, 
X% 
reduction in the specified 
the OP analysis period. 


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 Failure
o No migraine days of appropriate migraine severity in the OP. 
o Evaluable but < X% reduction in the month
 14 days of efficacy data 
and < X% reduction in the specified month. 
o 
X% reduction but not evaluable in the month
X% reduction 
to < 14 days of efficacy data in the specified month. 
o < X% reduction but not evaluable in the month, i.e., subjects with < X
to < 14 days of efficacy data in the specified month. 
o No days of efficacy data in the month. 
Outcomes categories for the overall DBT mean will be defined as follows: 
 
X% reduction in the overall DBT mean 
of appropriate migraine severity in the OP analysis period. 
 Failure  
o No migraine days of appropriate migraine severity in the OP. 
o < X% reduction, i.e., subjects with < X% reduction in the overall DBT mean. 
In the above description, X = 50,  75, and 100. Failure subcategories are mutually exclusive, 
because subjects who meet more than 1 failure criterion will be classified according to the first 
failure criterion met in the hierarchy above. 
The following histograms will be produced by treatment group for evaluable mITT subjects: 
 Percentage of subjects in categories of reduction from OP in the number of total migraine 
days per month in the last month of the DBT phase (y-axis) versus reduction category 
(x-axis). This is based on evaluable mITT subjects in Month 3. 
 Percentage of subjects in categories of reduction from OP in the number of total migraine 
days per month in the overall DBT mean (y-axis) versus reduction category (x-axis). 
Reduction categories are displayed in descending order: > 14; > 12 to  14; > 10 to  12; > 8 to 
 10; > 6 to  8; > 4 to  6; > 2 to  4; > 0 to  2; increase or no reduction in migraine 
days/month (ie.,  0). Histograms will include a vertical reference line between the last 2 
categories. Histograms were included as adhoc analyses in the CSR. 
Treatment Group Comparisons 
For each migraine severity (total; moderate or severe) and select percentage reductions 
%, 
 
the percentages of evaluable mITT subjects with reductions will be 
compared between treatment groups using Cochran-Mantel-Haenszel (CMH) tests stratified by 
prophylactic migraine medication use at randomization (yes, no). Response rates will be based 
on responder outcomes described previously. The following statistics will be presented for each 
month of the DBT phase and overall DBT mean by migraine severity: 


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 Response rate (“n/N”), risk (i.e., percentage), ASE, and 95% normal CI by randomization 
stratum for each treatment group 
 Overall response rate (“n/N”), stratified risk, ASE, and 95% normal CI for each treatment 
group 
 Difference in risks between treatment groups (rimegepant – placebo), ASE, 95% CI, and p-
value by randomization stratum 
 Difference in overall stratified risks between treatment groups (rimegepant – placebo), ASE, 
95% CI, and p-value.  
Results for  50% reduction of moderate or severe migraine severity in the last month (i.e., 
month 3) will support the first secondary objective. All other results will support exploratory 
objectives about percentage reductions.  
These endpoints will also be compared between treatment groups using unstratified CMH tests 
by migraine severity (total; moderate or severe) for each subgroup level of all efficacy subgroups 
of interest specified in Section 6.1.3.1 except prophylactic migraine medication use. For each 
migraine severity and subgroup level, the following statistics will be presented for each month in 
the DBT phase and overall DBT mean: 
 Response rate (“n/N”), risk (i.e., percentage), ASE, and 95% normal CI by treatment group  
 Difference in risks between treatment groups (rimegepant – placebo), ASE, 95% CI, and p-
value. 
Longitudinal plots will display the percentage of subjects with reduction (i.e., overall stratified 
risks on y-axis) versus month of the DBT phase (x-axis) for e
(total; moderate or severe). Error bars will 
denote 95% CIs. 
Percentages of Subjects With Reduction in Migraine Days per Month in the OLE Phase 
Analyses will be based on evaluable OL rimegepant mITT subjects with eDiary efficacy dates in 
the OP and on-OL rimegepant efficacy analysis periods.
The number and percentage of evaluable OL rimegepant mITT subjects with reductions from the 
OP in the number of migraine days per month in the OLE phase will be presented by treatment 
group and overall, and severity (total; moderate or severe) in each month of the OLE phase and 
overall OL mean (see Section 6.3.1.2 for months). Reduction from OP categories will be same as 
those defined previously for the DBT phase. Analyses by month will be presented using the 
analogous Non-Evaluable = Failure and Non-Evaluable = Missing methods described previously 
for the DBT phase. Analyses for the Non-Evaluable = Failure method will only be shown in the 
Addendum Report. Results will support the exploratory objective about OLE phase efficacy. 


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6.3.2.2 
Rescue Medication Days per Month
During the DBT and OLE phases, subjects may record taking triptan, ergotamine, and other 
medications to treat headache or during aura in the eDiary evening report headache log or 
follow-up headache log.  
Rescue medication days per month will be assessed as “rescue medication days per 4 weeks” to 
correspond with the 4-week visit schedule. Rescue medication days per month are based on data 
from the previous visit to the current visit (i.e., 4-week interval) where a rescue medication day 
is defined as a day of efficacy data with complete reference time point date and a “yes” response 
to at least one of the following questions: taking triptan to treat headache or during aura; taking 
ergotamine to treat headache or during aura; taking other medication to treat headache. 
Rescue Medication Days per Month in the DBT Phase 
Analyses are based on evaluable mITT subjects with eDiary reference time point dates in the on-
DBT efficacy analysis period.  
The number of rescue medication days per month in the DBT phase will be prorated to 28 days 
and derived as follows: 
 Month (i.e., 4-week interval) in the on-DBT efficacy analysis period: 28 × (total number of 
rescue medication days in the month)/(total number of efficacy data days in the month). 
Subjects must have  14 days of efficacy data (not necessarily consecutive) in the specified 
month to be evaluable. 
 Overall DBT mean: 28 × (total number of rescue medication days through Month 3 in the on-
DBT efficacy analysis period)/(total number of efficacy data days through Month 3 in the on-
DBT efficacy analysis period). 
Descriptive Analyses 
The number of rescue medication days per month in the DBT analysis period will be 
summarized descriptively as a continuous parameter (including 2-sided normal 95% CIs for 
mean) by treatment group in each month of the DBT phase and overall DBT mean.  
 
 
Treatment Group Comparisons 
A generalized linear mixed effect model will have the following variables: number of rescue 
medication days per month as the dependent variable; subject as a random effect; treatment 
group, prophylactic migraine medication use at randomization, month (i.e., months 1 to 3 of the 
DBT phase), and the month-by-treatment group interaction as fixed effects. The model will be 
repeated by prophylactic migraine medication use at randomization (yes, no). The following 
model estimates will be reported: 


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 LSM, SE, and 95% CI by month and randomization stratum (yes, no, overall) for each 
treatment group
 Difference in LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, and p-
value by randomization stratum (yes, no) for each month 
 Difference in LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, and p-
value for each month. Results in the last month will support the third secondary objective, 
whereas results in the other months will support an exploratory objective. 
 Overall LSM, SE, and 95% CI by randomization stratum (yes, no, overall) for each treatment 
group 
 Difference in overall LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, 
and p-value by randomization stratum (yes, no) 
 Difference in overall LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, 
and p-value. Results will support an exploratory objective. 
Rescue Medication Days per Month in the OLE Phase 
Analyses are based on evaluable OL rimegepant mITT subjects with eDiary reference time point 
dates in the on-OL rimegepant efficacy analysis period.  
The number of rescue medication days per month in the OLE phase will be prorated to 28 days 
and derived as follows: 
 Month (i.e., 4-week interval) in the on-OL rimegepant efficacy analysis period: 28 × (total 
number of rescue medication days in the month)/(total number of efficacy data days in the 
month). Subjects must have  14 days of efficacy data (not necessarily consecutive) in the 
specified month to be evaluable. 
 Overall OL rimegepant mean: 28 × (total number of rescue medication days through Month 
13 in the on-OL rimegepant efficacy analysis period)/(total number of efficacy data days 
through Month 13 in the on-OL rimegepant efficacy analysis period). 
The number of rescue medication days per month in the OLE phase will be summarized 
descriptively as a continuous parameter (including 2-sided normal 95% CIs for mean) by 
treatment group and overall in each month of the OLE phase and overall OLE mean.  
6.3.2.3 
MSQoL in the DBT Phase
The MSQoL will be assessed at early termination and the following visits: baseline; Week 12 of 
the DBT phase; and Weeks 24 and 64 of the OLE phase. 
The MSQoL consists of 14 items across the following 3 domains: (1) restrictive role function, (2) 
preventative role function and (3) emotional function. Refer to the BHV3000 Core SAP for 
calculating transformed domain scores and imputing missing data. 
Measurements will be first selected from the on-DBT efficacy period, and then slotted into the 
Week 12 analysis visit window (see Week 12 of the analysis visit window for outcome research 


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[OR] endpoints column in Table 4).  If a subject has multiple values in the analysis visit window, 
then the non-missing value closest to the target date for the visit will be used; in the case of a tie, 
the latest value collected will be used. 
See Sections 6.2.5, 7.4, and 7.5 for definitions of baseline, analysis periods, and analysis visit 
windows, respectively. 
Descriptive Analyses 
Values and changes from baseline in transformed scores for each domain will be summarized 
descriptively (included 2-sided normal 95% CIs for mean change) as continuous parameters by 
treatment group at baseline and Week 12.  
As-randomized analyses will be based on evaluable mITT subjects with MSQoL domain scores 
at both baseline and Week 12 of the on-DBT efficacy analysis period. See Section 6.6.1for as-
treated analyses of MSQoL in the DBT and OLE phases for treated subjects. 
Treatment Group Comparisons 
Analyses will be based on evaluable mITT subjects with MSQoL restrictive role function 
domain scores at both baseline and Week 12 of the on-DBT efficacy analysis period. 
A generalized linear model will have the following variables: Week 12 change from baseline in 
the restrictive role function transformed score as the dependent variable; baseline restrictive role 
function transformed score as a covariate; treatment group and the prophylactic migraine 
medication use at randomization as fixed effects. The model will be repeated by prophylactic 
migraine medication use at randomization (yes, no). The following model estimates will be 
reported: 
 LSM change from baseline at Week 12, SE, and 95% CI by randomization stratum (yes, no, 
overall) for each treatment group 
 Difference in LSM changes from baseline between treatment groups (rimegepant  placebo) 
at Week 12, SE, 95% CI, and p-value by randomization stratum (yes, no) 
 Difference in LSM changes from baseline between treatment groups (rimegepant  placebo) 
at Week 12, SE, 95% CI, and p-value. Results will support the fifth secondary objective. 
6.3.2.4 
MIDAS in the DBT Phase 
The MIDAS is a retrospective, patient-administered, 5-item questionnaire that measures 
headache-related disability as lost time due to headache from paid work or school, household 
work, and non-work activities. The MIDAS will be assessed at early termination and the 
following visits: baseline; Week 12 of the DBT phase; and Weeks 24 and 64 of the OLE phase. 
Refer to the BHV3000 Core SAP for calculating MIDAS scores (i.e., total, absenteeism, 
presenteeism, item) and imputing missing data. 
Measurements will be first selected from the on-DBT efficacy period, and then slotted into the 
Week 12 analysis visit window; see Section 6.3.2.3. 


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Descriptive Analyses 
Values and changes from baseline in total, absenteeism, presenteeism, and item scores will be 
summarized as described in Section 6.3.2.3. 
As-randomized analyses will be based on evaluable mITT subjects with MIDAS scores at both 
baseline and Week 12 of the on-DBT efficacy analysis period. See Section 6.6.2 for as-treated 
analyses of MIDAS in the DBT and OLE phases for treated subjects. 
Treatment Group Comparisons 
Analyses will be based on evaluable mITT subjects with MIDAS total scores at both baseline 
and Week 12 of the on-DBT efficacy analysis period. 
A generalized linear model will have the following variables: Week 12 change from baseline in 
the total score as the dependent variable; baseline total score as a covariate; treatment group and 
prophylactic migraine medication use at randomization as fixed effects. The model will be 
repeated by prophylactic migraine medication use at randomization (yes, no). The same model 
estimates as those described in Section 6.3.2.3 will be reported. Results will support the last 
secondary objective.
6.3.2.5 
Overall Summary of Primary and Secondary Endpoints  
An overall summary of treatment comparisons of all primary and secondary endpoints tested 
hierarchically will present the following statistics: 
 Continuous endpoints involving change from OP or baseline 
 Overall LSM change and 95% CI for each treatment group 
 Difference in overall LSM changes between treatment groups (rimegepant  placebo), 
95% CI, and p-value.  
This applies to the following endpoints: primary endpoint; secondary endpoint of change in 
mean number of migraine days per month in the overall DBT phase; secondary endpoint of 
change in mean number of migraine days per month in the first month of the DBT phase; 
MSQoL restrictive role domain score change from baseline at Week 12; and MIDAS total 
score change from baseline at Week 12. 
 Continuous endpoints not involving change from OP or baseline 
 Overall LSM and 95% CI for each treatment group 
 Difference in overall LSMs between treatment groups (rimegepant  placebo), 95% CI, 
and p-value. 
This applies to the secondary endpoint of the mean number of rescue medication days per 
month in the last month of the DBT phase. 
 Binary endpoints  
 Overall response rate (“n/N”), stratified risk, and 95% CI for each treatment group


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 Overall stratified risk difference between treatment groups (rimegepant – placebo), 95% 
CI, and p-value. 
This applies to the secondary endpoint of percentage of subjects with  50% reduction in 
mean number of moderate or severe migraine days per month in the last month of the DBT 
phase. 
Analyses will be based on principal methods described in Sections 6.3.1.1 and 6.3.2. Endpoints 
will be displayed in the order presented in Sections 1.2.1 and 1.2.2. P-values that are determined 
to be significant based on the testing hierarchy will be flagged. 
6.3.3 
Exploratory Efficacy Endpoints 
6.3.3.1 
Reduction in MRM Days per Month 
Female subjects will record their menstrual period start and stop dates in a menstrual period log. 
Menstruating females will be identified as females with either (1) a “yes” response to the 
question about experiencing menstrual periods on the Demographics CRF (see Section 6.2.5), or 
(2) at least one complete menstrual period start date from the Menstrual Period Log CRF. 
An eDiary reference time point date is considered to be exclusively in a menstrual interval if the 
complete menstrual period start date  2 days  eDiary reference time point date
complete 
menstrual period start date + 2 days.
A day of MR efficacy data is defined as a non-missing eDiary efficacy date inclusively in a 
menstrual interval.  
An MRM day is defined as a non-missing eDiary migraine date inclusively in a menstrual 
interval. 
MRM days per month will be assessed as “MRM days per 4 weeks” to correspond with the 4-
week visit schedule. MRM days per month are based on data from the previous visit to the 
current visit (i.e., 4-week interval), and are prorated to account for missing migraine reports. 
A by-subject listing of menstrual periods that includes efficacy analysis period will be provided 
for enrolled female subjects, and will display COVID-19 visit impact code for visits impacted by 
COVID-19 (see Section 9.1.5.2). 
A by-subject listing of MRM days will be provided for menstruating female treated subjects, and 
will present the following: number of MRM days per month by migraine severity (total; 
moderate or severe) in the OP efficacy analysis period, overall DBT mean, overall OL 
rimegepant mean, and in each month of the on-DBT and on-OL rimegepant efficacy analysis 
periods, number of days of MR efficacy data in these aforementioned periods, overall DBT 
mean, and overall OL rimegepant mean; MRM day values, changes and percent changes from 
OP in the aforementioned months, overall DBT mean, and overall OL rimegepant mean. 
Reduction in MRM Days per Month in the DBT Phase 


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The number of MRM days per month in the DBT phase will be examined relative to the number 
of MRM days per month in the OP for menstrual migraine evaluable mITT menstruating female 
subjects, i.e., mITT menstruating females with  1 day of eDiary MR efficacy data and  14 days 
of eDiary efficacy data (not necessarily consecutive) in both the OP analysis period and at least 
one month (i.e., 4-week interval) in the on-DBT efficacy analysis period (see Section 7.6.2).  
Months in the DBT phase are defined in Section 6.3.1.2. 
Analyses will be based on eDiary efficacy dates in the OP analysis period and on-DBT efficacy 
analysis period. 
The number of MRM days per month will be prorated to 28 days, and derived as follows: 
 OP: 28 × (total number of MRM days in the OP analysis period)/(total number of efficacy 
data days in the OP analysis period).  
 Month (i.e., 4-week interval) in the on-DBT efficacy analysis period: 28 × (total number of 
MRM days in the month)/(total number of efficacy data days in the month). Subjects must 
have at least one day of MR efficacy data in the specified month to be evaluable. 
 Overall DBT mean: 28 × (total number of MRM days through Month 3 in the on-DBT 
efficacy analysis period)/(total number of efficacy data days through Month 3 in the on-DBT 
efficacy analysis period). 
Missing MR Efficacy Data 
Missing MR efficacy data in the OP and DBT phases will be assessed using the number and 
percentage of mITT menstruating female subjects in the following categories:
 Evaluable 
 Not evaluable, i.e., no days of MR efficacy data in the OP and no days of MR efficacy data 
in all 3 months (i.e., all 3 4-week intervals) of the DBT phase 
 No days of MR efficacy data in the OP 
 No days of MR efficacy data in any of the following months (i.e., 4-week intervals) of 
the DBT phase: 
 
Month 1:  4 weeks 
 
Month 2: > 4 to  8 weeks 
 
Month 3: > 8 to  12 weeks 
Descriptive Analyses 
Values and changes (both absolute and percent) from the OP in the number of MRM days per 
month in the DBT phase will be summarized descriptively as continuous parameters (including 
2-sided normal 95% CIs for mean change) by treatment group and migraine severity (total; 
moderate or severe) in each month of the DBT phase and overall DBT mean.  


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Analyses are based on evaluable mITT menstruating female subjects. In the percent change 
analyses, subjects must also have  1 MRM day of appropriate migraine severity in the OP 
analysis period to be included. 
Treatment Group Comparisons 
A generalized linear mixed effect model similar to the one described for the primary endpoint in 
Section 6.3.1.1 will be used with the following variables: change from the OP in number of total 
MRM days per month as the dependent variable; subject as a random effect; number of total 
MRM days per month in the OP as a covariate; treatment group, prophylactic migraine 
medication use at randomization, month (i.e., months 1 to 3 of the DBT phase), and the month-
by-treatment group interaction as fixed effects. The model will be repeated by prophylactic 
migraine medication use at randomization (yes, no). The same model estimates will be reported 
as for the primary endpoint (see Section 6.3.1.1).  
Reduction in MRM Days per Month in the OLE Phase 
The number of MRM days per month in the OLE phase will be examined relative to the number 
of MRM days per month in the OP for menstrual migraine evaluable OL rimegepant mITT
menstruating female subjects, i.e., defined as OL rimegepant mITT menstruating female subjects 
with  1 day of MR efficacy data and  14 days of eDiary efficacy data (not necessarily 
consecutive) in both the OP analysis period and at least one month (i.e., 4-week interval) in the 
on-OL rimegepant efficacy analysis period.  
Months in the OLE phase are defined in Section 6.3.1.2. 
Analyses will be based on eDiary efficacy dates in the OP and on-OL rimegepant efficacy 
analysis periods. 
The number of MRM days per month will be prorated to 28 days and derived as follows: 
 OP: See Section 6.3.1.1. 
 Month (i.e., 4-week interval) in the on-OL rimegepant efficacy analysis period: 28 × (total 
number of MRM days in the month)/(total number of efficacy data days in the month). 
Subjects must have  1 day of MR efficacy data in the specified month to be evaluable. 
 Overall OL rimegepant mean: 28 × (total number of MRM days through Month 13 in the on-
OL rimegepant efficacy analysis period)/(total number of efficacy data days through Month 
13 in the on-OL rimegepant efficacy analysis period). 
Missing MR Efficacy Data 
Missing MR efficacy data in the OP and OLE phases will be assessed using the number and 
percentage of OL rimegepant mITT menstruating female subjects in the following categories: 
 Evaluable 


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 Not evaluable, i.e., no days of MR efficacy data in the OP and no days of MR efficacy data 
in all 13 months (i.e., all 13 4-week intervals) of the OLE phase 
 No days of MR efficacy data in the OP  
 No days of MR efficacy data in any of the following months (i.e., 4-week intervals) of 
the OLE phase: 
 
Months 1 to 3: > 12 to  24 weeks 
 
Months 4 to 6: > 24 to  36 weeks 
 
Months 7 to 9: > 36 to  48 weeks 
 
Months 10 to 13: > 36 to  64 weeks 
Descriptive Analyses 
Values and changes (both absolute and percent) from the OP in the number of MRM days per 
month in the OLE phase will be summarized descriptively as continuous parameters (including 
2-sided normal 95% CIs for mean change) by as-randomized treatment group and overall and 
migraine severity (total; moderate or severe) in each month of the OLE phase and overall OL 
rimegepant mean.  
Analyses are based on evaluable OL rimegepant mITT menstruating female subjects. In the 
percent change analyses, subjects must also have  1 MRM day of appropriate migraine severity 
in the OP analysis period to be included. 
6.3.3.2 
Reduction in Migraine Days in the First Week of the DBT Phase 
The number of migraine days in the first week of the DBT phase will be examined relative to the 
number of migraine days per week in the OP for evaluable first week mITT subjects, i.e., mITT 
subjects with at least one day of eDiary efficacy data in both the OP analysis period and the first 
week of the on-DBT analysis period.  
The first week of the DBT phase is defined as study days 1 to 7. See Sections 7.4 and 7.5 for the 
definition of analysis periods and study days used to define analysis visit windows.  
Analyses will be based on evaluable first week mITT subjects with eDiary efficacy dates in the 
OP analysis period and the on-DBT efficacy analysis period. 
The number of migraine days per week will be prorated to 7 days, and derived as follows: 
 OP: 7 × (total number of migraine days in the OP analysis period)/(total number of efficacy 
data days in the OP analysis period).  
 First week of the on-DBT efficacy analysis period: 7 × (total number of migraine days in the 
first week)/(total number of efficacy data days in the first week). Subjects must have at least 
one day of efficacy data in the first week to be evaluable. 
Descriptive Analyses 


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Values and changes (both absolute and percent) from the OP in the number of migraine days per 
first week of the DBT phase will be summarized descriptively as continuous parameters 
(including 2-sided normal 95% CIs for mean change) by treatment group and migraine severity
(total; moderate or severe). 
In the percent change analyses, subjects must also have  1 migraine day of appropriate severity 
in the OP analysis period to be included. 
Treatment Group Comparisons 
Analyses will be based on total severity, unless specified otherwise. 
A generalized linear model will use the following variables: change from the OP in number of 
total migraine days per week in the first week as the dependent variable; number of total 
migraine days per week in the OP as a covariate; treatment group and prophylactic migraine 
medication use at randomization as fixed effects. The model will be repeated by prophylactic 
migraine medication use at randomization (yes, no). The following model estimates will be 
reported: 
 LSM change from OP, SE, and 95% CI by randomization stratum (yes, no, overall) for each 
treatment group
 Difference in mean changes from OP between treatment groups (rimegepant  placebo), SE, 
95% CI, and p-value by randomization stratum (yes, no) 
 Difference in mean changes from OP between treatment groups (rimegepant  placebo), SE, 
95% CI, and p-value. Results will support the exploratory objective. 
These analyses will be repeated for moderate or severe migraine severity. All variables in the 
model will be the same, except (1) change from the OP in number of moderate or severe 
migraine days per week will be the dependent variable, and (2) number of moderate or severe 
migraine days per week in the OP will be the covariate. 
6.3.3.3 
Triptan or Ergotamine Days per Month 
This adhoc analysis was added to the CSR. 
Triptan or ergotamine days are a subset of rescue medication days (see Section 6.3.2.2). Triptan 
or ergotamine days per month will be assessed as “Triptan or ergotamine days per 4 weeks” to 
correspond with the 4-week visit schedule. Triptan or ergotamine days per month are based on 
data from the previous visit to the current visit (i.e., 4-week interval) where a triptan or 
ergotamine day is defined as a day of efficacy data with complete reference time point date and a 
“yes” response to at least one of the following questions: taking triptan to treat headache or 
during aura; taking ergotamine to treat headache or during aura.  
Triptan or Ergotamine Days per Month in the DBT Phase 


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Analyses are based on evaluable mITT subjects with eDiary reference time point dates in the on-
DBT efficacy analysis period.  
The number of triptan or ergotamine days per month in the DBT phase will be prorated to 28 
days and derived as follows: 
 Month (i.e., 4-week interval) in the on-DBT efficacy analysis period: 28 × (total number of 
triptan or ergotamine days in the month)/(total number of efficacy data days in the month). 
Subjects must have  14 days of efficacy data (not necessarily consecutive) in the specified 
month to be evaluable. 
 Overall DBT mean: 28 × (total number of triptan or ergotamine days through Month 3 in the 
on-DBT efficacy analysis period)/(total number of efficacy data days through Month 3 in the 
on-DBT efficacy analysis period). 
Descriptive Analyses 
The number of triptan or ergotamine days per month in the DBT analysis period will be 
summarized descriptively as a continuous parameter (including 2-sided normal 95% CIs for 
mean) by treatment group in each month of the DBT phase and overall DBT mean.  
Treatment Group Comparisons 
A generalized linear mixed effect model will have the following variables: number of triptan or 
ergotamine days per month as the dependent variable; subject as a random effect; treatment 
group, prophylactic migraine medication use at randomization, month (i.e., months 1 to 3 of the 
DBT phase), and the month-by-treatment group interaction as fixed effects. The model will be 
repeated by prophylactic migraine medication use at randomization (yes, no). The following 
model estimates will be reported: 
 LSM, SE, and 95% CI by month and randomization stratum (yes, no, overall) for each 
treatment group
 Difference in LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, and p-
value by randomization stratum (yes, no) for each month 
 Difference in LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, and p-
value for each month.  
 Overall LSM, SE, and 95% CI by randomization stratum (yes, no, overall) for each treatment 
group 
 Difference in overall LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, 
and p-value by randomization stratum (yes, no) 
 Difference in overall LSMs between treatment groups (rimegepant  placebo), SE, 95% CI, 
and p-value.  
Triptan or Ergotamine Days per Month in the OLE Phase 


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Analyses are based on evaluable OL rimegepant mITT subjects with eDiary reference time point 
dates in the on-OL rimegepant efficacy analysis period. 
The number of triptan or ergotamine days per month in the OLE phase will be prorated to 28 
days and derived as follows: 
 Month (i.e., 4-week interval) in the on-OL rimegepant efficacy analysis period: 28 × (total 
number of triptan or ergotamine days in the month)/(total number of efficacy data days in the 
month). Subjects must have  14 days of efficacy data (not necessarily consecutive) in the 
specified month to be evaluable. 
 Overall OL rimegepant mean: 28 × (total number of triptan or ergotamine days through 
Month 13 in the on-OL rimegepant efficacy analysis period)/(total number of efficacy data 
days through Month 13 in the on-OL rimegepant efficacy analysis period).
The number of triptan or ergotamine days per month in the OLE phase will be summarized 
descriptively as a continuous parameter (including 2-sided normal 95% CIs for mean) by 
treatment group and overall in each month of the OLE phase and overall OLE mean.  
6.3.3.4 
Medication Days per Month on Non-Scheduled Days in the OLE Phase 
This adhoc analysis was added to the CSR and further modified for the Addendum Report.  
See Section 7.6.2.3 for the definition of non-scheduled days in the OLE phase. 
Rescue medication is defined as triptan, ergotamine, or other medication (see Section 6.3.2.2). 
On non-scheduled days, either OL rimegepant or rescue medication can be taken.
For a given medication, the number of medication days per month on non-scheduled days for the 
overall OL rimegepant mean is defined as: 28 × (total number of medication days on the same 
days as non-scheduled days through Month 13 in the on-OL rimegepant efficacy analysis 
period)/(total number of non-scheduled days through Month 13 in the on-OL rimegepant efficacy 
analysis period). 
The number of medication days per month on non-scheduled days for the overall OL mean will 
be summarized descriptively as a continuous parameter for evaluable OL rimegepant mITT 
subjects by treatment group and overall for the following medications: 
 Any medication: rimegepant or rescue medication 
 Acute migraine medication, defined as rimegepant, triptan, or ergotamine 
 Rimegepant only 
 Rescue medication only 
 Rimegepant and rescue medication 
 Triptan or ergotamine only. 


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6.4 
Pharmacokinetic Evaluations 
No pharmacokinetic data were collected in this study. 
6.5 
Safety
Safety analyses will be tabulated by as-treated treatment group and overall, unless specified 
otherwise. Results for treated subjects on DBT will be tabulated by as-treated treatment group 
without overall treatment group. 
Safety outcome measures will include deaths, AEs, laboratory tests, vital signs, physical 
measurements, electrocardiograms (ECGs), and S-STS.  
Safety analysis periods are pre-treatment, pre-rimegepant treatment, on-DBT, on-OL rimegepant, 
on-treatment (on-DBT and on-OL rimegepant combined), on-rimegepant (DB or OL), post-DBT 
pre-OL rimegepant, and follow-up (see Section 7.4).  
 For the blinded interim analysis in the 90-Day Safety Update, safety analysis periods of 
primary interest will be on-DBT, on-OL rimegepant, on-treatment, and follow-up.  
 For unblinded analyses in CSRs, safety analysis periods of primary interest will be on-DBT, 
on-rimegepant, and follow-up. 
Measurements will be slotted into analysis periods based on “measurement date”, which is (1) 
imputed start date for AEs, (2) death date for deaths (see Section 7.3), and (3) collection or 
assessment date for all other safety parameters. 
Select safety parameters will be summarized as continuous parameters at baseline and each 
scheduled visit over time in the various safety analysis periods. Measurements will be slotted 
into safety analysis periods and analysis windows as follows: 
 For treated subjects, measurements will be first slotted into the on-DBT, on-OL rimegepant, 
and follow-up safety analysis periods. Next, measurements will be slotted into analysis visit 
windows in these analysis periods. 
 For rimegepant treated subjects, measurements will be first slotted into the on-rimegepant 
and follow-up safety analysis periods (see Section 7.4). Next, measurements will be slotted 
into analysis visit windows in these analysis periods. 
If a subject has multiple values in an analysis visit window in a safety analysis period, then the 
non-missing value in the analysis period closest to the target date for the visit will be used; in the 
case of a tie, the latest value collected (from the central laboratory, if applicable) will be used. 
Results will also be shown at EOT for each phase, i.e., last non-missing measurement in the on-
DBT, on-OL rimegepant, and on-DB or OL rimegepant safety analysis periods. Results will also 
be shown at end of follow-up (EOFU), i.e., last non-missing measurement in the follow-up safety 
analysis period.  
In analyses of the worst abnormality or category in a safety analysis period, subjects must have a 
non-missing measurement in the safety analysis period to be included for a given parameter. In 


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shift from baseline analyses, subjects must have a non-missing measurement at baseline and in
the safety analysis period to be included for a given parameter.    
See Sections 6.2.5, 7.4, and 7.5 for the definitions of baseline, safety analysis periods, and 
analysis visit windows, respectively. 
By-subject listings of safety data will include safety analysis period (i.e., pre-treatment, on-DBT, 
on-OL rimegepant, and follow-up), study day, rimegepant study day, COVID-19 visit impact 
code for visits impacted by COVID-19 (see Section 9.1.5.2), and are described in subsections. In 
addition, a by-subject listing of procedures will be provided for enrolled subjects. 
A by-subject listing of safety narrative subject identifiers will be provided for enrolled subjects 
with select events, as described in the BHV3000 Core SAP. The listing will flag subjects with 
select events. 
6.5.1 
Adverse Events 
Refer to the BHV3000 Core SAP for AE start date imputation, AE counting rules, definition of 
treatment-emergent adverse events (TEAEs), definition of exposure-adjusted multiple 
occurrences of unique AEs, definition of AEs related to study drug, and AE listing contents. 
AEs will be displayed in tables and listings by SOC and PT, unless specified otherwise. AEs by 
SOC and PT on DBT will be displayed in descending order of rimegepant frequency within SOC 
and PT, unless specified otherwise. AEs by SOC and PT on OL rimegepant, on rimegepant, on 
treatment, and during follow-up will be displayed in descending order of overall frequency 
within SOC and PT, unless specified otherwise. TEAEs on DBT are those that developed, 
worsened, or became serious on DBT relative to pre-treatment. TEAEs on DB or OL rimegepant 
are those that developed, worsened, or became serious on DB or OL rimegepant relative to pre-
rimegepant. TEAEs on OL rimegepant are those that developed, worsened, or became serious on 
OL rimegepant relative to pre-OL rimegepant. 
A by-subject listing of all AEs will be provided for enrolled subjects that will flag on-DBT 
TEAEs and on-OL rimegepant TEAEs. Additional by-subject AE listings will be provided for 
SAEs, AEs leading to study drug discontinuation for treated subjects, hepatic-related AEs, and 
AEs of special interest (i.e., potential drug abuse AEs, CV, suicidality).  
6.5.1.1 
Deaths 
Deaths will be identified from any of the following sources: 
 AE CRF: PT or reported term containing “death”, outcome of fatal, “yes” response to the 
question “Did the AE result in death?”, or non-missing death date. 
 DB Subject Status CRF: death as primary reason for phase completion/discontinuation; or 
death as reason for completing the DB phase through Week 12 and not entering the OL 
phase.  
 OL Subject Status CRF: death as primary reason for phase completion/discontinuation. 


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 Follow-up Subject Status CRF: death as primary reason for phase 
completion/discontinuation. 
Deaths will be tabulated by safety analysis period for enrolled subjects as follows: by treatment 
group for treated subjects; not treated; and overall. Counts will be displayed without percentages. 
A by-subject listing of deaths will be provided for enrolled subjects, and will display all CRF 
sources of death, safety analysis period, death date (see Section 7.3), study day derived from the 
death date, rimegepant study day derived from the death date, and the following AE parameters: 
non-imputed start date; end date; SOC; PT; verbatim term; outcome; and response to the 
question “Did the AE result in death?”.
6.5.1.2 
AE Overviews 
An AE overview without SOC and PT will present the number and percentage of subjects with 
any of the following AEs: any AE; mild AE; moderate AE; severe AE; AE related to study drug; 
SAE; SAE related to study drug; AE leading to study drug discontinuation; hepatic-related AE; 
severe hepatic-related AE; hepatic-related SAE; hepatic-related AE leading to study drug 
discontinuation; potential drug abuse AE; CV AE; and suicidality AE.  
An AE overview will be produced by treatment group and overall for each the following safety 
analysis periods and populations: 
 Pre-treatment for enrolled subjects (overall, not by treatment group) 
 Pre-treatment for treated subjects
 Pre-rimegepant for DB or OL rimegepant treated subjects 
 On-DBT for treated subjects (excluding overall) 
 On-DBT for treated subjects limited to on-DBT TEAEs (excluding overall) 
 On-DB or OL rimegepant for DB or OL rimegepant treated subjects 
 On-DB or OL rimegepant for DB or OL rimegepant treated subjects limited to on-DB or OL 
rimegepant TEAEs 
 Post-DBT pre-OL rimegepant for interim subjects 
 Follow-up for follow-up subjects. 
In addition, an AE overview will be produced by subgroup level and overall for all safety 
subgroups of interest described in Sections 6.1.3.3 and 6.1.3.4 for each the following safety 
analysis periods and populations:  
 On-DB or OL rimegepant for DB or OL rimegepant treated subjects 
 On-DB or OL rimegepant for DB or OL rimegepant treated subjects limited to on-DB or OL 
rimegepant TEAEs 
 On-OL rimegepant for OL rimegepant treated subjects 


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 On-OL rimegepant for OL rimegepant treated subjects limited to on-OL rimegepant TEAEs. 
6.5.1.3 
Pre-Treatment AEs 
Pre-treatment AEs will be summarized by SOC and PT for enrolled subjects (overall, not by 
treatment group) and the following endpoints: 
 AEs by severity (total, mild, moderate, severe, moderate or severe, not reported) 
 SAEs.  
Pre-treatment AEs will be summarized by SOC and PT for treated subjects by treatment group 
and overall and the following endpoints: 
 AEs by severity 
 SAEs. 
Pre-rimegepant AEs will be summarized for DB or OL rimegepant treated subjects analogously. 
6.5.1.4 
On-Treatment AEs 
DBT Phase 
On-DBT AEs will be summarized by SOC and PT for treated subjects by treatment group for the 
following endpoints: 
 AEs by severity  
 TEAEs by severity 
 TEAEs occurring with  2% frequency on rimegepant and greater than placebo after 
rounding. Percentages will be displayed rounded to integers, and AEs will be displayed in 
alphabetical order by SOC and PT. 
 AEs related to study drug by severity 
 AEs related to study drug occurring with  2% frequency in any treatment group 
 SAEs  
 AEs leading to study drug discontinuation 
 Hepatic-related AEs 
 Hepatic-related AEs leading to study drug discontinuation 
 Additional AEs of special interest: potential drug abuse, CV, and suicidality. Potential drug 
abuse AEs will be displayed in alphabetical order by severity and PT without SOC 
 Exposure-adjusted multiple occurrences of unique AEs (see Section 7.6.1) 
 Exposure-adjusted multiple occurrences of unique SAEs (see Section 7.6.1) 


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 Exposure-adjusted multiple occurrences of unique SAEs related to study drug (see 
Section 7.6.1) 
 Exposure-adjusted multiple occurrences of unique non-SAEs occurring with  5% frequency 
in any treatment group (see Section 7.6.1). 
AEs by severity will also be summarized analogously by subgroup level and overall for all safety 
subgroups of interest described in Section 6.1.3.2 for each treatment group.  
DB or OL Rimegepant Phase 
On-DB or OL rimegepant AEs will be summarized by SOC and PT for DB or OL rimegepant 
treated subjects by treatment group and overall for the same endpoints described above for the 
DBT phase. Data cuts (e.g.,  2%) will be applied to overall, not each treatment group. 
Exposure-adjusted multiple occurrences of unique AEs will be presented only by overall. 
In addition, on-DB or OL rimegepant AEs will be tabulated by SOC and PT for DB or OL 
rimegepant treated subjects by subgroup level and overall for all safety subgroups of interest 
described in Section 6.1.3.3 for the following endpoints: 
 AEs by severity 
 AEs occurring with  5% frequency by severity. The 5% cut applies only to total severity in 
overall (not in each subgroup level). 
 TEAEs by severity 
 TEAEs occurring with  2% frequency overall after rounding. Percentages will be displayed 
rounded to integers, and AEs will be displayed in alphabetical order by SOC and PT. 
 AEs related to study drug by severity 
 SAEs  
 AEs leading to study drug discontinuation 
 Additional AEs of special interest: hepatic-related AEs; potential drug abuse AEs, 
cardiovascular AEs, and suicidality AEs. Potential drug abuse AEs will be displayed in 
alphabetical order by severity and PT without SOC. 
OLE Phase and On-Treatment Phase (90-Day Safety Update Only) 
On-OL rimegepant AEs will be summarized by SOC and PT for OL rimegepant treated subjects 
by overall for the following endpoints: 
 AEs by severity  
 SAEs  
 AEs leading to study drug discontinuation. 
On-treatment AEs will be summarized analogously for treated subjects. 


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OLE Phase
On-OL rimegepant AEs will be summarized by SOC and PT for OL rimegepant treated subjects 
by subgroup level and overall for all safety subgroups of interest described in Section 6.1.3.4 for 
the following endpoints: 
 AEs by severity  
 AEs occurring with  5% frequency by severity. The 5% cut applies only to total severity in 
overall (not in each subgroup level). 
 SAEs  
AEs leading to study drug discontinuation. 
On-OL rimegepant AEs will be summarized by SOC and PT for OL rimegepant treated subjects 
by overall for the following endpoints (see Section 7.6.1): 
 Exposure-adjusted multiple occurrences of unique AEs  
 Exposure-adjusted multiple occurrences of unique SAEs  
 Exposure-adjusted multiple occurrences of unique SAEs related to study drug 
Exposure-adjusted multiple occurrences of unique non-SAEs occurring with  5% frequency. 
6.5.1.5
Follow-up AEs
Follow-up AEs will be summarized by SOC and PT for follow-up subjects by treatment group 
and overall for the following endpoints: 
 AEs by severity 
 SAEs. 
6.5.1.6
AEs Across All Study Phases Combined
AEs will be summarized by SOC and PT for treated subjects by treatment group and overall 
across all safety analysis periods combined for the following endpoints: 
 AEs leading to study drug discontinuation 
Hepatic-related AEs leading to study drug discontinuation. 
6.5.1.7 
Post-DBT Pre-OL Rimegepant AEs 
Post-DBT pre-OL rimegepant AEs will be summarized by SOC and PT for interim subjects by 
treatment group and overall for the following endpoints: 
AEs by severity
SAEs


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 AEs leading to study drug discontinuation. 
6.5.2 
Laboratory Tests 
Clinical safety laboratory testing will be performed at early termination and the following visits: 
screening; baseline; Weeks 4, 8, and 12 of the DBT phase; and Weeks 16, 24, 48 and 64 of the 
OLE phase. Urinalysis will be collected at early termination and the following visits: baseline; 
and Weeks 24 and 64 of the OLE phase. Lipids (i.e., cholesterol, high-density lipoprotein (HDL) 
cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides) will be collected at 
early termination and the following visits: baseline; and Weeks 24 and 64 of the OLE phase. 
LFTs (ALT, AST, alkaline phosphatase [ALP], TBL, and direct bilirubin) will be collected 
routinely at early termination and the following visits: screening; pre-randomization lab visit; 
baseline; Weeks 2, 4, 8, and 12 of the DBT phase; Weeks 14, 16, and every 4 weeks through 
Week 64 of the OLE phase; and follow-up Weeks 2 and 8. 
Clinically significant laboratory abnormalities will be identified as grade 3 to 4 laboratory test 
results. Refer to the BHV3000 Core SAP for laboratory tests of clinical interest and toxicity 
grading. Laboratory test groups of clinical interest will include hematology, serum chemistry, 
and urinalysis. 
LDL cholesterol and triglycerides will be analyzed as separate laboratory test parameters 
according to fasting status: fasting (i.e., fasting status of yes), not fasting (i.e., fasting status not 
equal to yes, including no, unknown, not reported, missing, etc.), and overall.  
Estimated glomerular filtration rate (eGFR) will be derived using the modification of diet in 
renal disease (MDRD) formula; refer to the BHV3000 Core SAP for additional details. 
Tables, listings, and figures (TLFs) will be provided to show data in both Systeme Internationale 
(SI) and United States (US) unit systems, if applicable.  
Tables will present results by treatment group (and overall if applicable), and laboratory tests 
alphabetically within laboratory test group, as applicable. 
By-subject listings of the following select laboratory test will be provided for enrolled subjects: 
hematology; serum chemistry (including eGFR derived using MDRD); urinalysis (US units 
only); pregnancy (US units only); endocrinology, serology, drug screen, and miscellaneous 
laboratory tests (US units only); and local laboratory CK fractionation. In addition, a by-subject 
listing of LFT values and ratios to ULN (i.e., ALT, AST, TBL and ALP) will also be provided 
for enrolled subjects, which will include all results over time for those with select elevations 
(ALT or AST > 3 x ULN; ALP or TBL > 2 x ULN) at any time point. COVID-19 visit impact 
code for visits impacted by COVID-19 will be displayed for each laboratory test of clinical 
interest in the following listings: hematology; serum chemistry; urinalysis; pregnancy (urine tests 
only); and LFT values and ratios to ULN. Refer to the BHV3000 Core SAP for listing content. 
6.5.2.1 
Laboratory Test Abnormalities
Refer to the BHV3000 Core SAP for toxicity grade categories and additional details. 


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Worst Laboratory Test Abnormalities 
The number and percentage of subjects with the worst (highest) laboratory test abnormality in a 
safety analysis period will be presented by treatment group (and overall if applicable) in toxicity 
grade categories separately for each graded laboratory test. 
Worst laboratory test abnormalities will be summarized for the following safety analysis periods 
and populations: on-DBT for treated subjects; on-DB or OL rimegepant for DB or OL 
rimegepant treated subjects; post-DBT pre-OL rimegepant for interim subjects; on-OL 
rimegepant for OL rimegepant treated subjects by overall for the 90-Day Safety Update only; on-
treatment for treated subjects by overall for the 90-Day Safety Update only; follow-up for 
follow-up subjects.  
Worst laboratory test abnormalities will also be summarized for the following safety analysis 
periods and populations  by subgroup level and overall for all safety subgroups of interest 
described in Sections 6.1.3.2, 6.1.3.3 and 6.1.3.4: on-DBT for treated subjects for each treatment 
group; on-DB or OL rimegepant for DB or OL rimegepant treated subjects; on-OL rimegepant 
for OL rimegepant treated subjects. 
Laboratory Test Toxicity Grade Shifts From Baseline to Worst Abnormality 
Laboratory test toxicity grade shifts from baseline to the worst (highest) toxicity grade in the 
safety analysis period will be summarized by treatment group (and overall if applicable) as the 
number and percentage of subjects in each toxicity grade category. 
Shifts will be summarized for the following safety analysis periods and populations: (1) on-DBT 
for treated subjects, and (2) on-DB or OL rimegepant for DB or OL rimegepant treated subjects, 
using DB or OL rimegepant baseline instead of baseline. 
Shifts will also be summarized for the following safety analysis periods and populations by 
subgroup level and overall for all safety subgroups of interest described in Sections 6.1.3.3 and 
6.1.3.4: on-DB or OL rimegepant for DB or OL rimegepant treated subjects, using DB or OL 
rimegepant baseline instead of baseline; on-OL rimegepant for OL rimegepant treated subjects, 
using OL rimegepant baseline instead of baseline. 
Laboratory Test Low/Normal/High Shifts From Baseline to any Abnormal Value 
Laboratory test low/normal/high shifts from baseline to any abnormal value in the safety analysis 
period will be summarized by treatment group (and overall if applicable) as the number and 
percentage of subjects in each category for laboratory tests with normal ranges.  
Shifts will be summarized for the following safety analysis periods and populations: (1) on-DBT 
for treated subjects, and (2) on-DB or OL rimegepant for DB or OL rimegepant treated subjects, 
using DB or OL rimegepant baseline instead of baseline. 
Shifts will also be summarized for the following safety analysis periods and populations by 
subgroup level and overall for all safety subgroups of interest described in Sections 6.1.3.3 and 


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6.1.3.4: on-DB or OL rimegepant for DB or OL rimegepant treated subjects, using DB or OL 
rimegepant baseline instead of baseline; on-OL rimegepant for OL rimegepant treated subjects, 
using OL rimegepant baseline instead of baseline. 
6.5.2.2 
LFT Elevations 
Subjects must have non-missing LFT data (i.e., ALT, AST, TBL, or ALP) in the safety analysis 
period to be included. 
Refer to the BHV3000 Core SAP for additional details. 
LFT Elevations 
The number and percentage of subjects with pre-specified cumulative, mutually exclusive, and 
composite LFT elevations will be summarized by treatment group (and overall if applicable) 
separately for the following safety analysis periods and populations:  
 Pre-treatment for treated subjects 
 Pre-rimegepant treatment for DB or OL rimegepant treated subjects 
 On-DBT for treated subjects (excluding overall) 
 On-DB or OL rimegepant for DB or OL rimegepant treated subjects 
 On-DB or OL rimegepant for DB or OL rimegepant treated subjects by subgroup level and 
overall for all safety subgroups of interest described in Sections 6.1.3.3 
 Post-DBT pre-OL rimegepant for interim subjects 
 On-OL rimegepant for OL rimegepant treated subjects by overall for the 90-Day Safety 
Update only 
 On-OL rimegepant for OL rimegepant treated subjects by subgroup level and overall for all 
safety subgroups of interest described in Sections 6.1.3.4 
 On-treatment for treated subjects by overall for the 90-Day Safety Update only 
 Follow-up for follow-up subjects. 
The following LFT elevations will be summarized for: (1) on-DBT for treated subjects, and (2) 
on-DB or OL rimegepant for DB or OL rimegepant treated subjects: 
 Exposure-adjusted cumulative LFT elevations with the number and percentage of subjects 
with LFT elevations, along with patient-years and exposure-adjusted rates based on exposure 
up to time of first LFT elevation (see Section 7.6.1).  
 Time to first LFT elevation with number and percentage of subjects with LFT elevations by 
time categories (weeks):  2, > 2 to  4, > 4 to  8, and additional 4-week intervals. LFT 
elevations are ALT > 3 x ULN, AST > 3 x ULN, and ALT or AST > 3 x ULN. Subjects must 
have an LFT elevation in the safety analysis period to be included. 
LFT ULN Shifts From Baseline to Worst Elevation 


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LFT ULN shifts from baseline to the worst (highest) elevation in the safety analysis period will 
be summarized by treatment group and overall as the number and percentage of subjects in pre-
specified LFT elevation categories. 
Shifts will be summarized for the following safety analysis periods and populations: (1) on-DBT 
for treated subjects; and (2) on-DB or OL rimegepant for DB or OL rimegepant treated subjects, 
using rimegepant baseline instead of baseline. 
Shifts will also be summarized for the following safety analysis periods and populations by 
subgroup level and overall for all safety subgroups of interest described in Sections 6.1.3.3 and 
6.1.3.4: on-DB or OL rimegepant for DB or OL rimegepant treated subjects, using DB or OL 
rimegepant baseline instead of baseline; on-OL rimegepant for OL rimegepant treated subjects, 
using OL rimegepant baseline instead of baseline. 
eDISH Scatter Plots 
An evaluation of drug-induced serious hepatotoxicity (eDISH) scatter plot will display the 
maximum TBL ratio of value to ULN (y-axis) versus the maximum ALT ratio of value to ULN 
(x-axis), where both maxima will be in the same safety analysis period but not necessarily 
concurrent. eDISH scatter plots will be produced by treatment group for the following safety 
analysis periods and populations: (1) on-DBT for treated subjects; (2) on-DB or OL rimegepant 
for DB or OL rimegepant treated subjects. 
eDISH scatter plots will also be produced for the following safety analysis periods and 
populations by mutually-exclusive subgroup level for all safety subgroups of interest described 
in Sections 6.1.3.3 and 6.1.3.4: on-DB or OL rimegepant for DB or OL rimegepant treated 
subjects; on-OL rimegepant for OL rimegepant treated subjects.  
By-Subject Longitudinal LFT Plots 
By-subject longitudinal plots will display ratios of values to ULN for AST, ALT, ALP, and TBL 
(y-axis) versus study week of the laboratory test result (x-axis) for treated subjects with any of 
the following LFT elevations in a safety analysis period (pre-treatment, on-treatment, follow-up): 
ALT > 3 x ULN, AST > 3 x ULN, TBL > 2 x ULN, or ALP > 2 x ULN. Study weeks are defined 
as study day/7, where study day is derived from the laboratory test collection date (see Section 
7.5). Each figure will also display DBT and OL rimegepant dosing days using symbols along the 
x-axis (see Section 7.6.2), start of DBT, start of OL rimegepant, and start of the follow-up safety 
analysis period using vertical lines.  
6.5.2.3 
Laboratory Test Changes From Baseline Over Time 
Values and changes from baseline in all hematology and serum chemistry laboratory tests will be 
summarized using descriptive statistics by treatment group and overall for treated subjects at the 
following time points: baseline; each scheduled visit through Week 12 and EOT of the on-DBT 
safety analysis period; each scheduled visit from Week 12 through EOT of the on-OL 
rimegepant safety analysis period; each scheduled visit and EOFU of the follow-up safety 
analysis period.  


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Values and changes from rimegepant baseline in all hematology and serum chemistry laboratory 
tests will be summarized analogously for DB or OL rimegepant treated subjects at the following 
time points: rimegepant baseline; each scheduled visit and EOT of the on-DB or OL rimegepant 
safety analysis period; each scheduled visit and EOFU of the follow-up safety analysis period. 
Note that scheduled visits vary according to laboratory test (see Section 6.5.2). 
6.5.3 
Vital Signs and Physical Measurements 
Vital signs and physical measurements will be measured at early termination and the following 
visits: screening; baseline; Weeks 4, 8, and 12 of the DBT phase; Week 16 and every 4 weeks 
through Week 64 of the OLE phase; and follow-up Week 2.  
Vital signs will include systolic blood pressure, diastolic blood pressure, heart rate, temperature, 
and respiratory rate. In summaries, only vital signs measured in the sitting position will be 
included. Physical measurements will include weight and BMI. 
A by-subject listing of vital signs and physical measurements will be provided for enrolled 
subjects. 
6.5.3.1 
Vital Sign and Physical Measurement Changes From Baseline Over Time 
Values and changes from baseline in vital sign and physical measurement parameters will be 
summarized as continuous parameters by treatment group and overall for treated subjects at the 
following time points: baseline; Weeks 4, 8, 12, and EOT of the on-DBT safety analysis period; 
Week 16, every 4 weeks through Week 64, and EOT of the on-OL rimegepant safety analysis 
period; follow-up Week 2 and EOFU of the follow-up safety analysis period. 
Values and changes from rimegepant baseline in vital sign and physical measurement parameters 
will be summarized analogously for DB or OL rimegepant treated subjects at the following time 
points: rimegepant baseline; Week 4, every 4 weeks through Week 64, and EOT of the on-DB or 
OL rimegepant safety analysis period; follow-up Week 2 and EOFU of the follow-up safety 
analysis period. 
6.5.3.2 
Vital Sign and Physical Measurement Abnormalities 
Vital sign and physical measurement abnormalities in safety analysis periods will be summarized 
by treatment group and overall as the number and percentage of subjects in prespecified 
categories defined in the BHV3000 Core SAP. 
Abnormalities will be summarized for the following safety analysis periods and populations: (1) 
on-DBT for treated subjects; (2) on-DB or OL rimegepant for DB or OL rimegepant treated 
subjects, using DB or OL rimegepant baseline instead of baseline for weight change; and (3) 
follow-up for follow-up subjects.  
Abnormalities will also be summarized for the following safety analysis periods and populations 
by subgroup level and overall for all safety subgroups of interest described in Sections 6.1.3.3 
and 6.1.3.4: on-DB or OL rimegepant for DB or OL rimegepant treated subjects, using DB or OL 


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rimegepant baseline instead of baseline for weight change; on-OL rimegepant for OL rimegepant 
treated subjects, using OL rimegepant baseline instead of baseline for weight change. 
6.5.4 
Electrocardiograms 
ECGs will be measured at early termination and the following visits: screening; baseline; Week 4
of the DBT phase; and Weeks 16, 24, 48, and 64 of the OLE phase; and follow-up Week 2. ECG 
parameters will include RR, QRS, PR, QT, QTcF, QTcB, and ventricular heart rate. 
A by-subject listing of ECG results will be provided for enrolled subjects. 
6.5.4.1 
ECG Changes From Baseline Over Time 
Values and changes from baseline in ECG parameters will be summarized as continuous 
parameters by treatment group and overall for treated subjects at the following time points: 
baseline; Week 4 and EOT of the on-DBT safety analysis period; Weeks 16, 24, 48, 64 and EOT 
of the on-OL rimegepant safety analysis period; follow-up Week 2 and EOFU of the follow-up 
safety analysis period. 
Values and changes from rimegepant baseline in ECG parameters will be summarized 
analogously for DB or OL rimegepant treated subjects at the following time points: rimegepant 
baseline; Weeks 4, 16,  24, 48, 64, and EOT of the on-DB or OL rimegepant safety analysis 
period; follow-up Week 2 and EOFU of the follow-up safety analysis period. 
6.5.4.2 
ECG Interpretation Shifts From Baseline to Worst Category 
The shift from baseline to worst ECG interpretation in safety analysis periods will be 
summarized by treatment group and overall as the number and percentage of subjects with 
normal, abnormal, and clinically significant abnormal interpretations. 
Shifts will be summarized for the following safety analysis periods and populations: (1) on-DBT 
for treated subjects; and (2) on-DB or OL rimegepant for DB or OL rimegepant treated subjects, 
using DB or OL rimegepant baseline instead of baseline. 
Shifts will also be summarized for the following safety analysis periods and populations by 
subgroup level and overall for all safety subgroups of interest described in Sections 6.1.3.3 and 
6.1.3.4: on-DB or OL rimegepant for DB or OL rimegepant treated subjects, using DB or OL 
rimegepant baseline instead of baseline; on-OL rimegepant for OL rimegepant treated subjects, 
using OL rimegepant baseline instead of baseline. 
6.5.4.3 
ECG Abnormalities 
ECG abnormalities in safety analysis periods will be summarized by treatment group and overall 
as the number and percentage of subjects in prespecified categories defined in the BHV3000 
Core SAP. 


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Abnormalities will be summarized for the following safety analysis periods and populations: (1) 
on-DBT for treated subjects, (2) on-DB or OL rimegepant for DB or OL rimegepant treated 
subjects, and (3) follow-up for follow-up subjects.  
Abnormalities will also be summarized for the following safety analysis periods and populations 
by subgroup level and overall for all safety subgroups of interest described in Sections 6.1.3.3 
and 6.1.3.4: on-DB or OL rimegepant for DB or OL rimegepant treated subjects, using DB or OL 
rimegepant baseline instead of baseline; on-OL rimegepant for OL rimegepant treated subjects, 
using OL rimegepant baseline instead of baseline. 
ECG abnormalities will be summarized together with vital sign and physical measurement 
abnormalities in the same tables (see Section 6.5.3.2). 
6.5.5 
Sheehan-Suicidality Tracking Scale
The S-STS is a prospective rating scale that contains 16 patient-reported questions and 6 
clinician-reported questions to track both treatment-emergent suicidal ideation and behaviors. 
The S-STS will be assessed at early termination and the following visits: screening; baseline; 
Weeks 2, 4, 8, and 12 of the DBT phase; Weeks 14, 16, and every 4 weeks through Week 64 of 
the OLE phase; and follow-up Weeks 2 and 8.  
S-STS scores are calculated as described in the BHV3000 Core SAP. 
Values and changes from baseline in the self-reported S-STS ideation subscale, behavior 
subscale, and total score will be summarized as continuous parameters at baseline and the worst 
(highest) score in safety analysis periods by treatment group and overall.  
In addition, the number and percentage of subjects in the worst (highest) score change from 
baseline category (i.e., < -1, -1, no change, 1, > 1) in safety analysis periods will also be 
presented by treatment group and overall for the ideation subscale, behavior subscale, and total 
score. 
S-STS scores, worst score changes from baseline, and worst score change categories from 
baseline will be summarized for the following safety analysis periods and populations: (1) on-
DBT for treated subjects; (2) on-DB or OL rimegepant for DB or OL rimegepant treated 
subjects, using DB or OL rimegepant baseline instead of baseline; and (3) follow-up for follow-
up subjects.  
A by-subject listing of the S-STS will be provided for enrolled subjects. Refer to the BHV3000 
Core SAP for the listing content. 
6.6 
Outcomes Research 
Analyses will be based on as-treated treatment group. 
OR (non-safety) questionnaires and rating scales are MSQoL, MIDAS, CGI-c, PoM, and SM 
(see Section 2.3.3). These will be assessed at early termination and the following visits: baseline 


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(MSQoL and MIDAS only), Week 12 of the DBT phase, and Weeks 24 and 64 of the OLE 
phase. 
Measurements will be slotted into analysis periods according to assessment dates. 
OR endpoints will be summarized descriptively over time. For treated subjects, measurements 
will be first slotted into the DBT OR and OL rimegepant OR analysis periods. Next, 
measurements will be slotted into analysis visit windows in these analysis periods.  If a subject 
has multiple values in an analysis visit window in an analysis period, then the non-missing value 
in the analysis period closest to the target date for the visit will be used; in the case of a tie, the 
latest value collected will be used. Results will also be shown at the “last visit” in each phase, 
i.e., last non-missing measurement in the DBT OR and OL rimegepant OR analysis periods, 
regardless of the analysis visit window.  
See Sections 6.2.5, 7.4, and 7.5 for definitions of baseline, OR analysis periods, and analysis 
visit windows, respectively. 
By-subject listings of OR questionnaires and rating scales (i.e., MSQoL, MIDAS, CGI-c, PoM, 
and SM) will be provided for enrolled subjects, and will include analysis period (pre-treatment, 
DBT OR, OL rimegepant OR), individual components, and COVID-19 visit impact code for 
visits impacted by COVID-19 (see Section 9.1.5.2). Refer to the BHV3000 Core SAP for the 
contents of the MSQoL and MIDAS listings. 
6.6.1 
MSQoL 
See Section 6.3.2.3 for the description of the MSQoL. 
Descriptive Analyses 
Values and changes from baseline in transformed scores for each domain will be summarized as 
continuous parameters (including 2-sided normal 95% CIs for mean change) by treatment group 
and overall for treated subjects at the following time points: baseline; Weeks 4, 12 and last visit 
of the DBT OR analysis period; and Weeks 24, 64, and last visit of the OL rimegepant OR 
analysis period.  
Treatment Group Comparisons 
This adhoc analysis was added to the CSR.   
Analyses are based on treated subjects with MSQoL domain scores at both baseline and Week 12 
of the DBT OR analysis period. For each MSQoL domain, the score change from baseline at 
Week 12 between treatment groups is compared using the same methodology as described in 
Section 6.3.2.3. 
6.6.2 
MIDAS 
See Section 6.3.2.4 for the description of the MIDAS. 


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Descriptive Analyses 
Values and changes from baseline in the total, absenteeism, presenteeism, and item scores will 
be summarized as continuous parameters (including 2-sided normal 95% CIs for mean change) 
by treatment group and overall for treated subjects at the following time points: baseline; 
Week 12 and last visit of the DBT OR analysis period; and Weeks 24, 64, and last visit of the OL 
rimegepant OR analysis period. 
Treatment Group Comparisons 
This adhoc analysis was added to the CSR. 
Analyses are based on treated subjects with MIDAS scores at both baseline and Week 12 of the 
DBT OR analysis period. For each MIDAS score (total, absenteeism, presenteeism), the score 
change from baseline at Week 12 between treatment groups is compared using the same 
methodology as described Section 6.3.2.4. 
6.6.3 
CGI-c Scale  
The CGI-c is an observer-rated 7-point scale that measures patient total improvement relative to 
the investigator’s past experience with other patients with the same diagnosis, with or without 
collateral information. The 7 improvement categories are: very much improved, much improved, 
minimally improved, no change, minimally worse, much worse, and very much worse.  
The number and percentage of treated subjects in each category (including combined categories) 
will be presented by treatment group and overall at the following time points: Week 12 and last 
visit of the DBT OR analysis period; and Weeks 24, 64, and last visit of the OL rimegepant OR
analysis period. Percentages for categories will be based on subjects with non-missing data at 
each visit along with 2-sided Agresti-Coull 95% CIs for each percentage. Refer to the BHV3000 
Core SAP for combined categories. 
6.6.4 
PoM 
The PoM is a 5-point rating scale that measures the patient’s preference of study medication to 
previous medications to treat migraine pain using the eDiary. The 5 preference categories are: 
much better, I prefer this medication; slightly better than the previous medication; about the 
same as the previous medication; slightly worse than the previous medication; and much worse, I 
prefer my previous medication.  
The number and percentage of treated subjects with PoM data and in each category (including 
combined categories) will be presented by treatment group and overall at the following time 
points: Week 12 and last visit of the DBT OR analysis period; and Weeks 24, 64 and last visit of 
the OL rimegepant OR analysis period. Percentages for categories will be based on subjects with 
non-missing data at each visit, along with 2-sided Agresti-Coull 95% CIs for each percentage. 
Refer to the BHV3000 Core SAP for combined categories. 


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6.6.5 
SM
The SM is a 7-point rating scale that measures the patient’s satisfaction with study medication to 
treat migraines using the eDiary. The 7 satisfaction categories are: completely satisfied, could 
not be better; very satisfied; somewhat satisfied; neither satisfied nor dissatisfied; somewhat 
dissatisfied; very dissatisfied; and completely dissatisfied, could not be worse.  
The number and percentage of treated subjects with survey data in each category (including 
combined categories) will be presented by treatment group and overall at the following time 
points: Week 12 and last visit of the DBT OR analysis period; and Weeks 24, 64, and last visit of 
the OL rimegepant OR analysis period. Percentages for categories will be based on subjects with 
non-missing data at each visit along with 2-sided Agresti-Coull 95% CIs for each percentage. 
Refer to the BHV3000 Core SAP for combined categories. 
6.7 
COVID-19 Impact 
COVID-19 impact will be assessed by treatment group and overall only for the combined 
population sample of OL rimegepant treated or follow-up subjects. Analyses are based on 
COVID-19 visit impact data with non-missing COVID-19 visit dates (see Section 7.3). 
Measurements will be slotted into safety analysis periods according to COVID-19 visit dates.  
When COVID-19 visit impact is summarized descriptively over time, measurements will be first 
slotted into safety analysis periods. Next, measurements will be slotted into analysis visits in 
these analysis periods (see Section 7.5).  
6.7.1 
COVID-19 Overall Impact 
COVID-19 overall impact will be tabulated as the number and percentage of subjects in the 
categories defined by COVID-19 visit impact type, visit impact characteristics, and visit impact 
relationship (see Section 9.1.1). In addition, for each of the 3 COVID-19 visit impact type 
categories (i.e., missed visit; in-person visit at site; remote visit), the number and percentage of 
subjects in the following subcategories defined by the number of visits impacted by COVID-19 
will be tabulated:  2 visits,  3 visits,  4 visits, etc. Visit counts are based on unique 
COVID-19 visit dates. Percentages are based on subjects with  1 visit with non-missing 
COVID-19 visit impact in the on-OL rimegepant or follow-up safety analysis period (see 
Section 9.1.3). 
6.7.2 
COVID-19 Impact Over Time 
COVID-19 visit impact will be tabulated over time at each analysis visit. The number and 
percentage of subjects in the categories defined by COVID-19 visit impact type, visit impact 
characteristics, and visit impact relationship will be presented at each analysis visit in the on-OL 
rimegepant and follow-up safety analysis periods. If a subject has multiple values (e.g., 
scheduled missed visit and unscheduled remote visit) in an analysis visit window, then all results 
will be presented. Percentages are based on subjects with  1 non-missing COVID-19 visit 
impact in the analysis visit window (see Section 9.1.3).  


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Missing LFT data impacted by COVID-19 will be tabulated over time at each analysis visit in 
the on-OL rimegepant and follow-up safety analysis periods as the number and percentage of 
subjects in the following categories: 
1. Missing LFT data, defined as missing values for all of the 4 following LFTs in the analysis 
visit window: ALT, AST, ALP, and TBL.  
2. Missing LFT data at visits impacted by COVID-19, i.e., meeting criteria (1) and having  1 
visit impacted by COVID-19 in the analysis visit window (see Section 9.1.3) 
3. Missing LFT data at missed visits due to COVID-19, i.e., meeting criteria (1), (2), and 
having  1 missed visit in the analysis visit window (see Section 9.1.1).
Percentages are based on evaluable subjects at each analysis visit. At an analysis visit in the on-
OL rimegepant safety analysis period, evaluable subjects are OL rimegepant treated subjects 
with (OL rimegepant end date – study drug start date + 1)  lower bound of the analysis visit 
window. At an analysis visit in the follow-up safety analysis period, evaluable subjects are 
follow-up subjects with (last contact date – study drug last date + 1)  lower bound of the 
analysis visit window.  
6.7.3 
COVID-19 Impact Listings 
A by-subject listing of COVID-19 impact codes by visit will display visits with abbreviated 
labels (e.g., W36 = OL rimegepant Week 36; FU2 = Follow-up Week 2) in separate columns. 
Spanning headers above the visits display the safety analysis period (OL rimegepant or follow-
up). Each column denotes an analysis visit and displays the COVID-19 visit impact code (see 
Section 9.1.5.1). If a subject has multiple COVID-19 visit impact codes in an analysis visit 
window, then results are displayed sorted by COVID-19 visit date and comma-concatenated 
across all COVID-19 visit dates in the analysis visit window (e.g., “#U,&M1” if “#U” has a visit 
date of 01MAY2020 and “&M1” has a visit date of 10MAY2020). Footnotes will describe the 
abbreviations in the COVID-19 visit impact code (see Section 9.1.5.2). 
A by-subject listing of COVID-19 visit impact will display analysis period, analysis visit, 
COVID-19 visit date, study day derived from COVID-19 visit date, rimegepant study day 
derived from COVID-19 visit date, visit impact status, visit type, visit impact type, visit impact 
characteristics, visit impact relationship with specify text, and premature study termination (see 
Section 9.1.1).  
7 CONVENTIONS 
7.1 
General 
7.1.1 
Output Layout 
Refer to the BHV3000 Core SAP for TLF layout conventions. 


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For the CSR and Addendum Report, a list of TLFs and unique TLF templates will be provided in 
the corresponding Mock TLF documents.  
For the 90-Day Safety Update, a list of TLFs will be provided in the 90-Day Safety Update List 
of Deliverables, which will cross-reference (but not display) TLF templates in the Mock TLF 
CSR document. Output will be by overall, not treatment group. 
7.1.2 
Duplicate Subjects 
Duplicate subjects are those who enrolled in a previous BHV3000 study or rescreened more than 
once in study BHV3000-305 (either as per protocol or due to non-compliance), and are assigned 
more than 1 subject identifier in the BHV3000 project. These subjects will be identified from the 
(1) Demographics CRF which captures the previous BHV3000 subject identifier, and (2) 
Rescreen CRF which captures the previous BHV3000-305 subject identifier. The following 
conventions will apply: 
 The unique subject identifier will be derived from the protocol number, site number, and 
subject number corresponding to the first randomization or treatment across all BHV3000 
studies in which the subject enrolled. Otherwise, the unique subject identifier will be derived 
from the subject identifier. 
 The raw datasets will contain data from all BHV3000-305 subject identifiers, with the unique 
subject identifier populated across records.
 The analysis datasets will contain data as follows: 
o If the subject was randomized or treated more than once in study BHV3000-305, then 
data from all subject identifiers corresponding to randomization or treatment in study 
BHV3000-305 will be included.  
o If the subject was randomized or treated only once in study BHV3000-305, then only 
data from the subject identifier corresponding to randomization or treatment in study 
BHV3000-305 will be included. 
o If the subject was not randomized or treated in study BHV3000-305, then only data from 
the subject identifier corresponding to the last enrollment in study BHV3000-305 will be 
included.  
o The unique subject identifier and previous BHV3000-305 subject identifier will be 
populated across records. 
 By-subject listings will display subject identifier, but not unique subject identifier. 
7.2 
Subgroups 
Not applicable. 
7.3 
Derived Dates 
Derived dates for defining analysis periods are defined as follows: 


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 eDiary reference time/point date/time: See Section 7.6.2.1. 
 eDiary dosing dates: 
 Study drug to treat headache or during aura date/time: Complete reference time point 
date/time from any of the following date/time questions: study medication to treat 
headache or during aura from the evening report headache log or follow-up headache log; 
additional study medication to treat headache or during aura from the evening report 
headache log. 
 Imputed OL rimegepant to treat headache date/time: Complete reference time point 
date/time from “yes” response to question about having already taken study medication to 
treat headache from the scheduled dosing report. Derived only if both of the following 
criteria are met: 
 
Reference time point date/time on or after the IWRS Week 12 kit assigned local 
date/time 
 
There are no complete reference time point dates on the same day as the “yes” 
response from any of the following questions: study medication to treat headache or 
during aura date/time from the evening report headache log or follow-up headache 
log; additional study medication to treat headache or during aura date/time from the 
evening report headache log; date of missed scheduled dosing report or evening 
report headache log from the medication reconciliation form; study medication 
date/time from the scheduled dosing report. 
 Study drug date/time: Study drug to treat headache or during aura date/time, imputed OL 
rimegepant to treat headache date/time, or complete reference time point date/time from 
any of the following questions: date of missed scheduled dosing report or evening report 
headache log from the medication reconciliation form (note that time is not collected); 
study medication date/time from the scheduled dosing report. 
 
DBT: Reference time point date/time before the IWRS Week 12 kit assigned local 
date/time (reference time point date before the IWRS Week 12 kit assigned local date
for medication reconciliation form data) or the IWRS Week 12 kit assigned local 
date/time missing  
 
OL rimegepant: Reference time point date/time on or after the IWRS Week 12 kit 
assigned local date/time (reference time point date on or after the IWRS Week 12 kit 
assigned local date for medication reconciliation form data) 
 Study drug start date/time: Earliest study drug date/time. 
 Study drug end date/time: Latest study drug date/time. 
 Study drug last date/time:  
 
Interim database lock: Study drug end date/time date derived only for subjects who 
have either (1) non-missing DB completion status on the DB Subject Status CRF, not 
continuing to OL on the DB Subject Status CRF, and missing OL rimegepant start 
date/time, or (2) non-missing OL completion status on the OL Subject Status CRF.  
 
Final database lock: Study drug end date/time. 


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 DBT start date/time: Earliest DBT study drug date/time. This should be equal to study 
drug start date/time. 
 DBT end date/time: Latest DBT study drug date/time. 
 DBT last date/time:  
 
Interim database lock or snapshot prior to Week 12 Interim Analysis database lock: 
DBT end date/time date derived only for subjects with non-missing DB study 
completion status on DB Subject Status CRF.  
 
Database locks at or after Week 12 Interim Analysis database lock: DBT end 
date/time. 
 OL rimegepant start date/time: Earliest OL rimegepant study drug date/time.  
 OL rimegepant end date/time: Latest OL rimegepant study drug date/time. 
 OL rimegepant last date/time: 
 
Database lock or snapshot prior to final database lock: OL rimegepant end date/time 
date derived only for subjects with non-missing OL study completion status on OL 
Subject Status CRF or non-missing follow-up study completion status on the Follow-
up Subject Status CRF. 
 
Final database lock: OL rimegepant end date/time. 
 DB or OL rimegepant start date/time: Study drug start date/time for subjects whose as-
treated treatment group is rimegepant; OL rimegepant start date/time for subjects whose 
as-treated treatment group is placebo. 
 DB or OL rimegepant end date/time: Study drug end date/time for subjects whose as-
treated treatment group is rimegepant; OL rimegepant end date/time for subjects whose 
as-treated treatment group is placebo. 
 DB or OL rimegepant last dose date/time: Study drug last date/time for subjects whose 
as-treated treatment group is rimegepant; OL rimegepant last date/time for subjects 
whose as-treated treatment group is placebo. 
 Other eDiary dates: 
 Headache start date/time: Complete reference time point date/time from the headache 
start question from the evening report headache log. 
 Headache end date/time: Complete reference time point date/time from the headache end 
question from the evening report headache log or follow-up headache log.  
 Efficacy date: (1) Complete reference time point date from any question from the evening 
report headache log or follow-up headache log, or (2) non-missing OL rimegepant date 
on a non-scheduled day (see Sections 7.6.2.2 and 7.6.2.3). 
 OP start date: Earliest reference time point date from the OP epoch. 
 OP end date: Latest reference time point date from the OP epoch. 
 Miscellaneous composite dates 


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 Last DBT visit date: Maximum of the following: (1) latest eDiary reference time point 
date < OL rimegepant start date; (2) latest complete visit date from Visit Date CRF 
records without “follow-up” in foldername and visit date < OL rimegepant start date. 
This will be used to assess eDiary compliance. 
 Last OLE visit date: Maximum of the following: (1) latest eDiary reference time point 
date  OL rimegepant start date; (2) latest complete visit date from Visit Date CRF 
records without “follow-up” in foldername and visit date  OL rimegepant start date. 
This will be used to assess eDiary compliance. 
 Last DB or OL rimegepant visit date: Maximum of last DBT visit date and last OLE visit 
date for subjects whose as-treated treatment group is rimegepant; last OLE visit date/time 
for subjects whose as-treated treatment group is placebo. This will be used to assess 
eDiary compliance. 
 Last contact date: (1) Earliest complete death date from the AE CRF, if it exists; (2) 
otherwise, the maximum complete date of the following: AE start/stop; COVID-19 visit 
only for in-person or remote visits; ECG; eDiary reference time point; informed consent; 
IWRS randomization; laboratory collection; menstrual period start/stop; non-study 
medication start/stop; physical measurement; procedure; rating scale; questionnaire; 
study completion/discontinuation from Subject Status CRF (DBT, OLE, follow-up); vital 
sign; visit. 
 COVID-19 visit date: (1) Complete record date, if it exists; otherwise, complete date the visit 
was planned to occur for a missed visit (see Section 9.1.1).  
 Death date: Last contact date derived only for subjects who died (see Section 6.5.1.1).
No imputations are performed on these derived dates. Complete dates are those with valid, non-
missing day, month, and year.  
See Section 7.6.2.1 for the reference time point date/time and epoch derivations. 
7.4 
Analysis Periods 
Analysis periods are defined as follows: 
 eDiary efficacy endpoints (migraine days, rescue medication days), based on the date part of 
derived date/times 
 OP: Reference time point date in the OP epoch (see Section 7.6.2.1). 
 On-DBT efficacy: Reference time point date in the DBT epoch on or before the DBT last 
date + 1 day. This period is used to assess efficacy during the DBT phase. 
 Post-DBT pre-OL rimegepant efficacy: Reference time point date in the DBT epoch after 
the DBT last date + 1 day. This period is used only in eDiary efficacy listings. 
 On-OL rimegepant efficacy: Reference time point date in the OLE epoch on or before the 
OL rimegepant last date + 1 day. This period is used to assess efficacy during the OLE 
phase. 


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 Follow-up efficacy: Reference time point date in the OLE epoch after the OL rimegepant 
last date + 1 day. This period is used only in eDiary efficacy listings.
OR efficacy endpoints (MSQoL, MIDAS)
 On-DBT efficacy: Measurement date after the DBT start date through the earlier of (1) 
DBT last date + 1 day and (2) OL rimegepant start date. This period is used to assess OR 
efficacy during the DBT phase for evaluable mITT subjects. 
 Pre-treatment characteristics and safety endpoints 
Pre-treatment: Measurement date/time on or before the study drug start date/time. Note 
that AEs with imputed start date equal to the study drug start date are not part of this 
period (refer to the BHV3000 Core SAP for AE start date imputation). This period is 
used to derive baseline values and to assess pre-treatment safety endpoints. 
 Pre-rimegepant: Measurement date/time on or before the DB or OL rimegepant start 
date/time. Note that AEs with imputed start date equal to the DB or OL rimegepant start 
date are not part of this period. This period is used to derive rimegepant baseline values 
and to assess pre-rimegepant safety endpoints for DB or OL rimegepant treated subjects. 
 On-DBT safety: Measurement date/time after the DBT start date/time through the earlier 
of DBT last date + 7 days and OL rimegepant start date/time. Note that AEs with imputed 
start date equal to the DBT start date are part of this period, while AEs with imputed start 
date equal to the OL rimegepant start date are not part of this period. This period is used 
to assess safety endpoints on DBT. 
 Post-DBT pre-OL rimegepant safety: Measurement date/time after the DBT last date 
+ 7 days through the OL rimegepant start date/time. Note that AEs with imputed start 
date equal to the OL rimegepant start date are not part of this period. This period is used 
in safety listings to distinguish measurements, and to assess safety endpoints during the 
interim period (i.e., post-DBT pre-OL rimegepant) for interim subjects (i.e., those with 
> 7-day gap between DBT last date and OL rimegepant start date).  
 On-OL rimegepant safety: Measurement date/time after the OL rimegepant start 
date/time through the study drug last date + 7 days. Note that AEs with imputed start date 
equal to the OL rimegepant start date are part of this period. This period is used in safety 
listings to distinguish measurements, and to assess safety endpoints for OL rimegepant 
treated subjects in the blinded 90-Day Safety Update. 
 On-DB or OL rimegepant safety: Measurement date/time after the DB or OL rimegepant 
start date/time through the DB or OL rimegepant last date + 7 days. Note that AEs with 
imputed start date equal to the DB or OL rimegepant start date are part of this period. 
This period is used to assess safety endpoints on DB or OL rimegepant treatment for DB 
or OL rimegepant treated subjects. 
 On-treatment safety: Measurement date/time after the study drug start date/time through 
the study drug last date + 7 days. Note that AEs with imputed start date equal to the study 
drug start date are part of this period. This period is the on-DBT and on-OL rimegepant 
safety periods combined, and will be used to assess safety endpoints for treated subjects 
in the blinded 90-Day Safety Update. 


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 Follow-up safety: Measurement date after the study drug last date + 7 days. This period is 
used to assess safety endpoints during follow-up for follow-up subjects. 
Non-efficacy OR endpoints (see Section 6.6) 
 DBT OR: Measurement date after the DBT start date to the OL rimegepant start date. 
This period is used to assess OR during the DBT phase. 
 OL rimegepant OR: Measurement date after the OL rimegepant start date. This period is 
used to assess OR during the OLE phase. 
See Section 7.3 for derived dates for determining analysis periods.  
If measurement time is missing or not collected for a parameter, then the measurement date will 
be compared to the derived date.  
7.5 
Analysis Visit Windows 
Refer to BHV3000-305 Protocol Section 4.3 (Tables 1 and 2) for the schedule of assessments.  
Randomization days are calculated from randomization as follows: 
 Measurement date  IWRS randomization date + 1, if measurement date  IWRS 
randomization date 
 Measurement date  IWRS randomization date, if measurement date < IWRS randomization 
date. 
Study days are calculated from study drug start as follows: 
 Measurement date  study drug start date + 1, if measurement date  study drug start date 
 Measurement date  study drug start date, if measurement date < study drug start date. 
Rimegepant study days are calculated from DB or OL rimegepant start as follows: 
 Measurement date  DB or OL rimegepant start date + 1, if measurement date  DB or OL 
rimegepant start date 
 Measurement date  DB or OL rimegepant start date, if measurement date < DB or OL 
rimegepant start date. 
Follow-up days are calculated from the study drug last as follows: 
 Measurement date  study drug last date + 1, if measurement date/time  study drug last date 
 Measurement date  study drug last date, if measurement date < study drug last date. 
Analysis visit windows presented in Table 4 below are based on study days (see Section 7.4).  
Table 4: 
Analysis Visit Windows for Non-Efficacy Endpoints 


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Analysis Period 
Analysis Visit 
Abbreviation in Listings 
Analysis Day 
Analysis Visit Window  
Target Day 
Pre-Treatment
PRETRT
Randomization Day 
Screening 
 
 -7 or missing 
 
Pre-Randomization 
Prerand 
-6 to -1 
 
Randomization 
Rand 
1 
 
Post-Randomization 
Postrand 
 2 
 
OR/On-Treatment Safety * 
OR: DBT or OLRMG 
Safety: DBT, INT, or 
OLRMG 
Study Day 
 
Week 2 
 
1 to 21 
14 
Week 4
22 to 42
28
Week 8
43 to 70
56
Week 12 
 
71 to 91 
84 
Week 14 
 
92 to 105 
98 
Week 16 
 
106 to 126 
112 
Week 20 
 
127 to 154 
140 
Week 24 
 
155 to 182 
168 
Week 28 
 
183 to 210 
196 
Week 32 
 
211 to 238 
224 
Week 36 
 
239 to 266 
252 
Week 40 
 
267 to 294 
280 
Week 44 
 
295 to 322 
308 
Week 48 
 
323 to 350 
336 
Week 52
351 to 378
364
Week 56 
 
379 to 406 
392 
Week 60 
 
407 to 434 
420 
Week 64 
 
435 to 462 
448 
Extension # 
Ext 
 463 
476 
Follow-up Safety 
FU 
Follow-up Day 
 
Follow-up Week 2 
FU Week 2 
8 to 21 
14 
Follow-up Week 8 
FU Week 8 
22 to 70 
56 
Follow-up Extension # 
FU Ext 
 71 
84 
* OR includes the DBT and OL rimegepant OR analysis periods; on-treatment safety includes the DBT, interim, and 
OL rimegepant safety analysis periods.   
# Denotes an extended visit in the analysis period and is displayed only in listings 


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Study days are used to define analysis visit windows in all analysis periods except on-rimegepant 
and follow-up safety. Rimegepant study days are used to define analysis visit windows in the on-
DB or OL rimegepant safety analysis period. Follow-up days are used to define analysis visit 
windows in the follow-up safety analysis period. 
Analysis visit windows in the on-DB or OL rimegepant safety analysis period are defined 
analogously to those in the on-treatment safety analysis period. 
7.6 
Domain-Specific Derivations 
7.6.1 
Adverse Events 
Refer to the BHV3000 Core SAP for exposure-adjusted multiple occurrences of unique AEs. 
Exposure-adjusted multiple occurrences of unique AE calculations will be based on the 
following reference dates according to safety analysis period: 
 On-DBT: reference start date is DBT start date, reference end date is DBT end date, and 
reference last date is earlier of (1) DBT last date + 7 days and (2) OL rimegepant start date – 
1 day. 
 On-OL rimegepant: reference start date is OL rimegepant start date, reference end date is OL 
rimegepant end date, and reference last date is OL rimegepant last date + 7 days. 
 On-DB or OL rimegepant: reference start date is DB or OL rimegepant start date, reference 
end date is DB or OL rimegepant end date, and reference last date is DB or OL rimegepant 
last date + 7 days. 
 On-treatment: reference start date is the study drug start date, reference end date is study drug 
end date, and reference last date is study drug last date + 7 days. 
7.6.2 
eDiary 
7.6.2.1 
eDiary Reference Time Point Date and Epoch 
Reference Time Point Date Derivation
Reference time point date/time and epoch will only be derived for records with non-missing 
standard format character result/finding values. 
 Evening report headache log 
o Select headache-related characteristics and non-study medication parameters with the 
same finding date/time: The reference time point date/time will be set to the headache 
start date/time, if not missing.  
Parameters will include the following: headache (yes, no); headache start date/time; 
aura only event (yes, no); headache last at least 30 minutes (yes, no); severity (none, 
mild, moderate, severe); unilateral (yes, no); pulsate (yes, no); worsen or avoid 
physical activity (yes, no); nausea (yes, no); vomiting (yes, no); photophobia (yes, 


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no); phonophobia (yes, no); aura (yes, no); triptan (yes, no); ergotamine (yes, no); 
other medication (yes, no). 
o Headache end date/time and headache end (ended, still continuing) parameters with the 
same finding date/time: The reference time point date/time will be set to headache end 
date/time, if the headache end date/time is not missing. 
o Study medication for headache or aura parameters with the same finding date/time: The 
reference time point date/time will be set to the study medication for headache or aura 
date/time, if not missing. 
 Parameters will include the following: study medication for headache or aura (yes, 
no); study medication for headache or aura date/time; number of tablets taken; 
confirm number of tablets taken (yes, no). 
o Additional study medication for headache or aura parameters with the same finding 
date/time: The reference time point date/time will be set to additional study medication 
for headache date/time, if not missing. 
 Parameters will include the following: additional study medication for headache (yes, 
no); additional study medication for headache or aura date/time; number of additional 
tablets taken; confirm number of additional tablets taken (yes, no). 
 Follow-up headache log 
o Headache end date/time and headache continuing (yes, no) parameters with the same 
finding date/time: The reference time point date/time will be set to headache end 
date/time, if not missing. 
o Non-study medication triptan and ergotamine parameters: The reference time point 
date/time will be set to the last non-missing headache start date/time from evening report 
headache logs with finding date/time  24 hours at or before the follow-up headache log 
finding date/time.  
o Study medication for headache parameters with the same finding date/time: The 
reference time point date/time will be set to the study medication for headache or aura 
date/time, if not missing.  
 Parameters will include the following: study medication for headache or aura (yes, 
no); study medication for headache or aura date/time; number of tablets taken; 
confirm number of tablets taken (yes, no). 
 Scheduled dosing report parameters with the same finding date/time: The reference time 
point date/time will be set to the study medication date/time, if not missing. 


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 Parameters will include the following: took study medication today (yes, no); study 
medication date/time; number of tablets taken; confirm number of tablets taken (yes, 
no). 
 Medication reconciliation form date missed and number of tablets taken parameters with the 
same finding date/time: The reference time point date/time will be set to the date missed, if 
not missing. Note that time will be missing. 
Otherwise, the reference time point date/time will be set to the eDiary finding date/time.  
Epoch Derivation 
Epoch is defined based on the date part of derived date/times, as follows: 
 OP: Reference time point date before the DBT start date or DBT start date missing  
 DBT: (1) Reference time point date on or after the DBT start date and before the OL 
rimegepant start date, or (2) reference time point date on or after the DBT start date, if OL 
rimegepant start date missing 
 OLE: Reference time point date on or after the OL rimegepant start date. 
7.6.2.2 
eDiary Migraine Days 
For migraine day analyses, a day of efficacy data is defined as any non-missing eDiary efficacy 
date (see Section 7.3).  
A migraine day is defined as a day of efficacy data with either (1) or (2): 
1) Qualified migraine headache based on the following criteria per BHV3000-305 Protocol Appendix 3: 
o “Yes” response to the question about having a headache# with complete reference time 
point date/time#, or non-missing headache start date/time# (see Section 7.3) 
o Last
, defined as any of the following: 
 
 
 Headache end date/time# – 
, where headache 
end date/time and headache start date/time have the same finding date/time 
 Finding date/time# – 
and headache end status 
is still continuing#, where headache start date/time and headache end status have the 
same finding date/time 
 Headache end date/time@ – headache start date/time#  30 minutes, where headache 
end date/time is from the follow-up headache log with earliest finding date/time  24 
hours on or after the finding date/time of a still continuing headache from the 
evening report headache log   
o Meeting at least one of the following criteria (a or b): 


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a. 
 based on “yes” response to questions with the 
same finding date/time: 
i. Unilateral location#,
ii. Pulsating quality (throbbing)#, 
iii. Moderate or severe pain intensity# 
iv. Aggravation by or causing avoidance of routine physical activity (e.g. walking or 
climbing stairs)# 
b. 
 based on “yes” response to questions with 
the same finding date/time: 
i. Nausea# 
ii. Vomiting# 
iii. Both photophobia# and phonophobia# 
2) No qualified migraine headache but meeting either of the following criteria: 
a. Non-missing date/time of (1) study drug to treat headache or during aura#@ during the 
on-DBT efficacy analysis period, or (2) OL rimegepant on a non-scheduled day during 
the on-OL rimegepant efficacy analysis period (see Sections 7.3 and 7.6.2.3).  
b. “Yes” response to the question about taking triptan to treat headache or during aura #@ 
or question about taking ergotamine to treat headache or during aura #@, along with 
complete reference time point date/time#@, in the on-DBT efficacy or on-OL rimegepant 
efficacy analysis period.  
Date/time parameters and questions marked with “#” are identified from the evening report 
headache log.  Date/time parameters and questions marked with “@” are identified from the 
follow-up headache log. 
Migraine dates are determined from complete reference date/times based on eDiary parameters 
above. 
Only unique days of efficacy data are included in analyses. If there are multiple responses on the 
same day, then the most severe migraine will be chosen. 
7.6.2.3 
Scheduled and Non-Scheduled Days in the OLE Phase 
All days in the on-OL rimegepant efficacy analysis period are classified as either scheduled or 
non-scheduled days. Scheduled days are defined as days in the planned EOD dosing schedule. 
All other days are considered to be non-scheduled days. 
For each OL rimegepant treated subject, the initial planned EOD dosing schedule pattern is 
classified as even or odd with respect to the OL rimegepant start date as follows: 
 Calculate planned OL rimegepant day = scheduled report date – OL rimegepant start date for 
each scheduled report date in the on-OL rimegepant efficacy analysis period.  


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o A scheduled report date is a complete eDiary finding date from a “yes” response to either 
(1) question about having already taken study medication today to treat headache from 
the scheduled dosing report, or (2) question about taking a scheduled dose of study 
medication today from the scheduled dosing report.  
 If the first planned OL rimegepant day is an even number or missing, then the initial planned 
EOD dosing schedule pattern is even.  
 If the first planned OL rimegepant day is an odd number, then the initial planned EOD 
dosing schedule pattern is odd. 
It is expected that scheduled days follow the initial planned EOD dosing schedule for the entire 
OLE phase. Thus, if the initial planned EOD dosing schedule pattern is even, then it is expected 
that scheduled days are all even planned OL rimegepant days 0, 2, 4, etc. Otherwise, if the initial 
planned EOD dosing schedule pattern is odd, then it is expected that scheduled days are all odd 
planned OL rimegepant days 1, 3, 5, etc.  
However, in rare cases, the eDiary may reset at scheduled report dates and switch planned EOD 
dosing schedule patterns. For example, the planned EOD dosing schedule may start as even, 
switch to odd, and then switch back to even. A switch date is defined as a scheduled report date 
with an odd number of days between it and the previous scheduled report date. Switch dates 
define blocks of days within the on-OL rimegepant efficacy analysis period as follows:  
 Block 1: All days in the OL rimegepant efficacy analysis period before the first switch are 
considered to follow the initial planned EOD dosing pattern.  
 Block 2: All days on or after the first switch but before the second switch are considered to 
follow the second planned EOD dosing pattern. If there is only 1 switch, then all days on or 
after the first switch are considered to follow the second planned EOD dosing pattern. 
 Block 3: All days on or after the second switch but before the third switch are considered to 
follow the initial planned EOD dosing pattern. If there are only 2 switches, then all days on 
or after the second switch are considered to follow the initial planned EOD dosing pattern. 
This iterative process continues as needed. 
Example: 
 Subject has 26 days in the on-OL rimegepant efficacy analysis period, i.e., OL rimegepant 
start date on day 0 and OL rimegepant last date + 1 on day 25. 
 Scheduled report dates fall on planned OL rimegepant days 0, 2, 4, 8, 9, 11, 15, 18, 22, and 
24.  
o The initial EOD dosing schedule pattern is even. 
o There are 2 switches: day 9 is the first switch and day 18 is the second switch. 
o All even days from 0 to 8 inclusive (i.e., days 0, 2, 4, 6, 8) are scheduled days.  
o All odd days from 9 to 17 inclusive (i.e., days 9, 11, 13, 15, 17) are scheduled days. 
o All even days from 18 to 24 inclusive (i.e., 18, 20, 22, 24) are scheduled days. 


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o All other days (i.e., days 1, 3, 5, 7, 10, 12, 14, 16, 19, 21, 23, and 25) are non-scheduled 
days. 
Note that (1) imputed OL rimegpant dates and (2) OL rimegepant dates from the scheduled 
dosing report can only be on scheduled days. OL rimegepant dates from the evening report 
headache log, follow-up headache log, or medication reconciliation form can be on scheduled or 
non-scheduled days. 
7.6.3 
Non-Study Medications 
Non-study medication types will include prior, previous, current, DBT concomitant, OL 
rimegepant concomitant, DB or OL rimegepant concomitant, and follow-up. 
Prior medications are defined as those taken before study drug start, i.e., imputed start or stop 
date < study drug start date. These include the following subtypes: 
 Previous medications, defined as those taken before informed consent, i.e., those with an 
imputed start or stop date < informed consent date 
 Current medications, defined as those taken on or after informed consent and before study 
drug start, i.e., those with (1) informed consent date  imputed start or stop date < study drug 
start date or (2) imputed start date  informed consent date < study drug start date - 1  
imputed stop date. 
DBT concomitant medications are defined as those taken with DBT, i.e., (1) DBT start date  
imputed start or stop date  minimum of {DBT last date, OL rimegepant start date - 1}, or (2) 
imputed start date  DBT start date  minimum of {DBT last date, OL rimegepant start date - 1} 
 imputed stop date. 
OL rimegepant concomitant medications are defined as those taken with OL rimegepant, i.e., (1) 
OL rimegepant start date 
imputed start or stop date  OL rimegepant last date, or (2) imputed 
start date OL rimegepant start date  OL rimegepant last date  imputed stop date. 
DB or OL rimegepant concomitant medications are defined as those taken with DB or OL 
rimegepant, i.e., (1) DB or OL rimegepant start date  imputed start or stop date  DB or OL 
rimegepant last date, or (2) imputed start date  DB or OL rimegepant start date  DB or OL 
rimegepant last date  imputed stop date. 
Follow-up medications are defined as those taken after study drug discontinuation, i.e.,  study 
drug last date < imputed start or stop date. 
Listings will display abbreviated medication types. Note that a medication may be classified into 
multiple types. 


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7.7 
Age at a Reference Date 
Age at a reference date (e.g., laboratory collection date) will be calculated using the birth date as 
follows: 
 Let BD, BM, and BY respectively denote the numeric day, month, and year of the birth date. 
 Let RD, RM, and RY respectively denote the numeric day, month, and year of the reference 
date. 
 Age is defined as RY – BY, if either (1) RM > BM, or (2) RM = BM and RD  BD; 
otherwise, age is RY – BY – 1. 
Both the birth date and reference date must be complete. 
Note that age at informed consent will be calculated as above by an external data management 
vendor, and provided in the raw demographics dataset. 
8 CHANGES TO PLANNED ANALYSES IN THE PROTOCOL 
There are no changes to planned analyses in the protocol at this time.  
 


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9 APPENDICES 
9.1
COVID-19 Visit Impact
Analyses are based on the COVID-19 Visit Impact CRF.  
9.1.1 
COVID-19 Visit Impact CRF Description 
At each visit (scheduled or unscheduled), sites are required to complete the COVID-19 Visit 
Impact CRF, either retrospectively for visits on or after 01MAR2020 or prospectively.  
Unscheduled visits are identified from folder names containing “unscheduled”. Otherwise, all 
other visits are considered scheduled. In listings, the COVID-19 visit type is abbreviated as “U” 
for unscheduled visits and blank (i.e., missing) otherwise. 
COVID-19 visit impact status is based on the response to the lead question “Was this visit 
impacted by COVID-19 related issues? (yes or no)”. In listings, the COVID-19 visit impact 
status is abbreviated as “&” for yes and “#” for no. 
If the response to the lead question is “yes”, then responses to the following questions may be 
provided:  
 COVID-19 visit impact type: What was the impact? (Indicate one): 
o Missed visit – no assessments done [abbreviated as “M” in listings]
o In-person visit at site [abbreviated as “I” in listings] 
o Remote visit [abbreviated as “R” in listings]
 COVID-19 visit impact characteristics: 
o If missed visit, date visit planned to occur [used to derive the COVID-19 visit date] 
o If in-person visit at site: (Mark all that apply) 
 Not all assessments completed [abbreviated as “A” in listings]
 Scheduled visit occurring earlier or delayed relative to protocol specified schedule 
[abbreviated as “S” in listings] 
o If remote visit, then indicate nature of contact with subject: (Indicate one) 
o Virtual visit (video/telemedicine) [abbreviated as “V” in listings] 
o Telephone contact [abbreviated as “T” in listings] 
o If remote visit, was investigational product (IP) shipped to the subject? (yes; no) 
[abbreviated as “Y” for yes, “N” for no in listings] 
 COVID-19 visit impact relationship: How was the impact related to COVID-19? (Mark all 
that apply) 
o Subject diagnosed with COVID-19 or quarantined due to COVID-19 [abbreviated as “1” 
in listings]


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o Site closed or access restricted due to COVID-19 [abbreviated as “2” in listings] 
o Site open but subject unwilling or unable to come to the site due to COVID-19 
[abbreviated as “3” in listings]
o Other [abbreviated as “4” in listings], with specify text 
 COVID-19 premature study termination: If the subject is terminating the study prematurely, 
was the termination related to COVID-19? (yes; no; not applicable, subject continuing) 
[abbreviated as “X” for yes, “Z” for no, and blank otherwise in listings]. 
9.1.2 
COVID-19 Impact 
A subject is impacted by COVID-19 if there is a “yes” response to the lead question at  1 visit. 
9.1.3 
COVID-19 Visit Impact 
A visit is impacted by COVID-19 if there is a “yes” response to the lead question at that visit 
(see Section 9.1.1). 
A visit is not impacted by COVID-19 if there is a “no” response to the lead question at that visit. 
9.1.4 
COVID-19 Premature Phase Termination
An OL rimegepant treated subject terminated the OLE phase prematurely due to COVID-19 if all 
of the following criteria are met: “yes” response to the COVID-19 premature study termination 
question at 1 visit (see Section 9.1.1); did not complete the OLE phase (see Section 6.2.3.4); 
and missing response to the question about completing all follow-up visits on the Follow-up 
Subject Status CRF. Reasons for termination are based on the reasons for not completing the 
OLE phase. 
A follow-up subject terminated the follow-up phase prematurely due to COVID-19 if all of the 
following criteria are met: “yes” response to the COVID-19 premature study termination 
question at  1 visit (see Section 9.1.1); did not complete the follow-up phase (see 
Section 6.2.3.5). Reasons for termination are based on the reasons for not completing the follow-
up phase. 
9.1.5 
COVID-19 Visit Impact Code 
9.1.5.1 
COVID-19 Visit Impact Code Derivation 
At each visit, the COVID-19 visit impact code is derived as follows: 
 If the visit is impacted by COVID-19, then the value is the concatenation of the COVID-19 
abbreviations described in Section 9.1.1 in the following order:  
1) Visit impact status (i.e., lead question response): “&” 
2) Visit type: “U” if unscheduled 
3) Visit impact type: “M”, “I”, or “R” 


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4) Visit impact characteristics: “A”, “N”, “S”, “T”, “V”, or “Y”. Multiple responses may be 
selected. 
5) Visit impact relationship: 1, 2, 3, or 4. Multiple responses may be selected. 
6) Premature study termination: “X” or “Z”.  
Examples: 
o “&UIAS24X” if visit type is unscheduled, visit impact type is in-person visit, visit impact 
characteristics are “Not all assessments completed” and “Scheduled visit occurring earlier 
or delayed relative to protocol specified schedule”, visit impact relationships are “Site 
closed or access restricted due to COVID-19” and “Other”, and premature study 
termination is yes.
o “&RTY1” if visit type is scheduled, visit impact type is remote visit, visit impact 
characteristics are “Telephone contact” and “IP shipped to subject” , visit impact 
relationship is “Subject diagnosed with COVID-19 or quarantined due to COVID-19”, 
and premature study termination is not applicable. 
 If the visit is not impacted by COVID-19, then the value is the concatenation of the visit 
impact status “#” and the visit type (“U” if unscheduled). 
 Otherwise, the value is blank (i.e., missing). 
9.1.5.2 
COVID-19 Visit Impact Code in Listings 
Select by-subject listings of measurements over time will display all COVID-19 visit impact 
codes for visits impacted by COVID-19 as additional data records (see Section 9.1.3). Refer to 
the Mock TLF CSR document for more details. 
COVID-19 measurements will be slotted into analysis periods and analysis visit windows 
according to the COVID-19 visit date (see Sections 7.3 through 7.5). 
In the listing of COVID-19 impact codes by visit, footnotes will describe the abbreviations in the 
COVID-19 visit impact code, e.g., “COVID-19 visit impact code: & = Impacted; # = Not 
impacted; A = Not all assessments done; I = In-person visit at site; M = Missed visit; N = IP not 
shipped to subject; R = Remote visit; S = Scheduled visit early or late; T = Telephone; U = 
Unscheduled; V = Virtual; X = Premature termination due to COVID-19; Y = IP shipped to 
subject; Z = Premature termination not due to COVID-19; 1 = Subject dx or quar.; 2 = Site 
closed or restricted access; 3 = Site open but subject unwilling/unable to come to site; 4 = 
Other”. 
 

Prot_000.pdf: 
Protocol BHV3000-305
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DRUG:
BHV-3000 (rimegepant)
STUDY NUMBER(S):
BHV3000-305
PROTOCOL(S) TITLE:
BHV3000-305: A Phase 2/3, Randomized, Double-
blind, Placebo-controlled Study to Evaluate the 
Efficacy and Safety of Rimegepant in Migraine 
Prevention
IND NUMBER:
109886
SPONSOR:
Biohaven Pharmaceuticals, Inc.
ORIGINAL PROTOCOL 
DATE:
27 July 2018
VERSION NUMBER:
V09
VERSION DATE:
25 August 2020
NCT Number: NCT03732638


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CLINICAL PROTOCOL APPROVAL FORM
Protocol Title: A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the 
Efficacy and Safety of Rimegepant in Migraine Prevention
Study No: BHV3000-305
Original Protocol Date: 27 July 2018
Protocol Version No: V09 (Amendment 08)
Protocol Version Date: 25 August 2020
This study protocol was subject to critical review and has been approved by the 
appropriate protocol review committee of the sponsor.  The information contained in this 
protocol is consistent with:

The current risk-benefit evaluation of the investigational product.

The moral, ethical and scientific principles governing clinical research as set out in 
the Declaration of Helsinki, and principles of GCP as described in 21 CFR parts 50, 
54, 56 and 312 and according to applicable local requirements.
The Investigator will be supplied with details of any significant or new findings, 
including adverse events, relating to treatment with the investigational product.


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SUMMARY OF CHANGES
Change
Section(s) Affected
Summary (changes are noted in bold)
Allow for Study 
Medication to be 
shipped to a subject 
due to COVID-19 
Pandemic
Section 4.3 / Table 2 / Footnote 6
Original Wording:
6 Subjects should finish a bottle of study 
medication before starting a new bottle.  
Study drug will be dispensed at monthly 
(every 4 weeks) study visits, as needed.  
Unscheduled visits to dispense study 
medication may be scheduled as needed.  
Updated Wording:
6 Subjects should finish a bottle of study 
medication before starting a new bottle.  
Study drug will be dispensed at monthly 
(every 4 weeks) study visits, as needed.  
Unscheduled visits to dispense study 
medication may be scheduled as needed.  Due 
to the COVID-19 Pandemic, study 
medication may be shipped to a subject, 
with up to an 8-week supply.  Proper 
documentation must be maintained in the 
subject’s source records including shipping 
vendor, tracking number, confirmation of 
receipt by subject, and all other relevant 
information.
Rationale:
This change was included to allow flexibility 
in cases where the COVID-19 Pandemic 
impacts study visits.
Allow for Remote 
Visits (ex: Telephone, 
Telemedicine) due to 
COVID-19 Pandemic
Section 4.3 / Table 2 / Footnote 
10
Original Wording:
10 While on-study, all visit windows are used 
for scheduling purposes and all efforts should 
be made to return subjects to the 28-day 
schedule if scheduling changes are made at 
any previous visit(s).  
Updated Wording:
10 While on-study, all visit windows are used 
for scheduling purposes and all efforts should 
be made to return subjects to the 28-day 
schedule if scheduling changes are made at 
any previous visit(s).  Due to the COVID-19 
Pandemic, visits may be conducted 
remotely (ex: telephone, telemedicine) and 
must be documented within the source 
records as being conducted remotely.  All 
procedures not able to be completed due to 
a visit being conducted remotely must be 


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reported as a protocol deviation and can be 
performed at the next visit, where 
appropriate to do so based on subject 
presentation.  In cases where a Week 64 / 
End of Treatment (EOT) visit occurs
remotely in order to be completed during 
the protocol required window and due to 
the COVID-19 Pandemic, the subject 
should return to the site within the 8 Week 
Follow-up Safety Visit timeframe (8 weeks 
from last dose, -2 to +14 days), to complete 
all procedures that weren’t able to be 
completed remotely.  Procedures completed 
at the Week 64 / EOT Remote Visit do not 
need to be repeated.
Rationale:
This change was included to allow flexibility 
in cases where the COVID-19 Pandemic 
impacts study visits.
Allow for Remote 
Visits (ex: Telephone, 
Telemedicine) due to 
COVID-19 Pandemic
Section 4.3.3 / Open-label 
Extension Phase (52 weeks)
New wording: 
Due to the COVID-19 Pandemic, visits may 
be conducted remotely (ex: telephone, 
telemedicine) and must be documented 
within the source records as being 
conducted remotely.  All procedures not 
able to be completed due to a visit being 
conducted remotely must be reported as a 
protocol deviation and can be performed at 
the next visit, where appropriate to do so 
based on subject presentation.  
Allow for flexibility 
and to ensure 
completion of the 
Week 64 visit due to 
visits being impacted 
by the COVID-19 
Pandemic
Section 4.3.4 / End of Treatment 
(Week 64) 
Original Wording:
Subjects will return to the study at the end of 
Week 64 (±3 days), or at end of treatment for 
early discontinuations, for review of the 
electronic diary, assessment of medication 
compliance, assessment of tolerability and 
safety (including vital signs, laboratory tests,  
and  electrocardiography) (Table 2).  Subjects 
will return the unused study medication and 
electronic subject diary to the study site. 
Subjects who do not complete the Double-
blind, Treatment Phase and/or do not enter or 
complete the Open-label, Extension Phase 
should complete the End of Treatment Visit, 
2-Week Follow up Safety Visit and 8-Week 
Follow up Safety Visit.
Updated Wording:


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Subjects will return to the study at the end of 
Week 64 (±3 days), or at end of treatment for 
early discontinuations, for review of the 
electronic diary, assessment of medication 
compliance, assessment of tolerability and 
safety (including vital signs, laboratory tests,  
and  electrocardiography) (Table 2).  In cases 
where a Week 64 / End of Treatment 
(EOT) visit occurs remotely in order to be 
completed during the protocol required 
window and due to the COVID-19 
Pandemic, the subject should return to the 
site within the 8 Week Follow-up Safety 
Visit timeframe (8 weeks from last dose, -2 
to +14 days), to complete all procedures 
that weren’t able to be completed remotely.  
Procedures completed at the Week 64 / 
EOT Remote Visit do not need to be 
repeated.  Subjects must return the unused 
study medication and electronic subject diary 
to the study site. Subjects who do not 
complete the Double-blind, Treatment Phase 
and/or do not enter or complete the Open-
label, Extension Phase should complete the 
End of Treatment Visit, 2-Week Follow up 
Safety Visit and 8-Week Follow up Safety 
Visit.
Rationale:
This change was included to allow flexibility 
in cases where the COVID-19 Pandemic 
impacts study visits and reinforces 
requirement for unused study medication to be 
returned.
Allow for flexibility 
and to ensure 
completion of the 8-
Week Follow-up 
Safety Labs due to 
visits being impacted 
by the COVID-19 
Pandemic
Synopsis / Study Schematic
Section 4.2 / Figure 1 / Study 
Schematic
Section 4.3 / Table 2 / Header 
titled: 8-Week Follow-up Safety 
Visit (8 weeks ±2 days after EOT 
visit)
Section 4.3.6 / 8-Week Follow up 
Safety Visit
Original Wording:
8-Week Follow-up Safety Visit (8 weeks ±2 
days after EOT visit)
Updated Wording:
8-Week Follow-up Safety Visit (8 weeks (-2 
to +14 days) after EOT visit)
Rationale:
This change was included to allow flexibility 
to the final safety follow-up visit in cases 
where the COVID-19 Pandemic impacts this 
visit, requiring it to be conducted remotely at 
the 8-week follow-up timepoint.  Subjects 
should be contacted at the 8-week follow-up 
timepoint to collect safety information, per 
protocol, and then should return to the office 


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within 2 weeks to have the laboratory tests 
completed.  Tests may also be performed 
locally, if needed, in cases where a study site 
is not open to laboratory test collection.
Corrected 
Typographical Errors 
and Made Wording
Clarifications
Protocol Version 8
Corrected typographical errors and clarified 
wording throughout the document


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BHV3000-305
BHV3000-305: A Phase 2/3, Randomized, Double-blind, 
Placebo-controlled Study to Evaluate the Efficacy and Safety 
of Rimegepant in Migraine Prevention
CONFIDENTIALITY AND INVESTIGATOR STATEMENT
The information contained in this protocol and all other information relevant to
BHV-3000 (rimegepant) are the confidential and proprietary information of Biohaven 
Pharmaceuticals, Inc., and except as may be required by federal, state or local laws or 
regulation, may not be disclosed to others without prior written permission of Biohaven 
Pharmaceuticals, Inc.
I have read the protocol, including all appendices, and I agree that it contains all of the 
necessary information for me and my staff to conduct this study as described. I will 
conduct this study as outlined herein, in accordance with the regulations stated in the 
Federal Code of Regulations for Good Clinical Practices and International Conference on 
Harmonization guidelines, and will make a reasonable effort to complete the study within 
the time designated.
I will provide all study personnel under my supervision copies of the protocol and any 
amendments, and access to all information provided by Biohaven Pharmaceuticals, Inc. 
or specified designees. I will discuss the material with them to ensure that they are fully 
informed about BHV-3000 and the study.
_________________________________
_____________________________
Principal Investigator Name (printed)
Signature
___________ ___________
Date
Site Number


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STUDY SUMMARY (SYNOPSIS)
Title: 
A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to
Evaluate the Efficacy and Safety of Rimegepant in Migraine 
Prevention
Rationale: 
Rimegepant is being developed for the treatment of migraine. 
Effectiveness for the acute treatment of migraine was initially 
demonstrated in a Phase 2b double-blind, randomized, placebo-
controlled, dose-ranging study where rimegepant at 75 mg showed 
efficacy on all four traditional endpoints: pain, nausea, photophobia 
and phonophobia.1 Efficacy was confirmed in two pivotal Phase 3 
trials using the current registrational co-primary endpoints of Pain 
Freedom and Freedom from Most Bothersome Symptom at 2 hours 
after dosing.
This study is being conducted to evaluate the efficacy, safety, and 
tolerability of rimegepant for the prevention of migraine.
Target 
Population:
The study will recruit male and female subjects, 18 years of age or 
older with at least a one-year history of migraine (with or without aura) 
consistent with a diagnosis according to the International Classification 
of Headache Disorders, 3rd edition.2 Per their own report, subjects
must have migraine onset prior to age 50, migraine attacks that last 
4-72 hours (if not treated) and have had, 4-18 migraine attacks of 
moderate to severe intensity per 4 weeks period within the 12 weeks
prior to the screening visit. After a 28-day observation period of 
standard of care, up to approximately 800 eligible subjects will be 
randomized to receive rimegepant or placebo, with dosing on an every 
other day (EOD) dosing schedule.  At the completion of the 12-week 
double-blind, treatment phase, subjects will be evaluated for entry into 
the 52-week open label, extension phase if laboratory test results meet
protocol entry criteria (Table 2).
Number of 
Subjects:
Approximately 1500 subjects will be screened to randomize up to 
approximately 800 subjects to rimegepant or placebo.  It is estimated 
that approximately 675 subjects will be entered into the open-label 
extension phase.   


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Objectives: 
Primary Objective: 

To compare the efficacy of rimegepant to placebo as a preventive 
treatment for migraine, as measured by the reduction from baseline in 
the mean number of migraine days per month in the last 4 weeks of the 
double-blind treatment phase. (A month is defined as 4 weeks for the 
purpose of this protocol.)
Secondary Objectives:

To compare the efficacy of rimegepant to placebo on the 
proportion of subjects that have at least a 50% reduction from baseline 
in the mean number of moderate to severe migraine days per month in 
the last 4 weeks of the double-blind treatment phase.

To compare the efficacy of rimegepant to placebo on the reduction 
from baseline in the mean number of migraine days per month over the 
entire course of the double-blind treatment phase.

To compare the frequency of use of rescue medications between 
rimegepant and placebo in the last 4 weeks of the double-blind 
treatment phase.

To compare the efficacy of rimegepant to placebo on the reduction 
from baseline in the mean number of migraine days per month in the 
first 4 weeks of the double-blind treatment phase.

To evaluate the safety and tolerability of rimegepant.

To evaluate the frequency of ALT or AST > 3x ULN with 
concurrent elevations in bilirubin > 2x ULN in subjects treated with 
rimegepant.

To evaluate the frequency of hepatic-related adverse events (AEs) 
and the frequency of hepatic-related treatment discontinuations in 
subjects treated with rimegepant. 

To compare the change from baseline in the Migraine-Specific 
Quality-of-Life Questionnaire v 2.1 (MSQ) role function - restrictive 
domain score at Week 12 of the double-blind treatment phase between 
rimegepant and placebo.

To compare the change from baseline in the Migraine Disability 
Assessment (MIDAS) total score at Week 12 of the double-blind 
treatment phase between rimegepant and placebo.


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Study Design: This is a multicenter, randomized, double-blind, placebo-controlled 
study to assess the efficacy and safety of rimegepant in migraine 
prevention with an open-label extension phase.  
The Screening phase includes a screening visit and a 28-day 
Observation Period. For subjects to be eligible for the study, they must 
report having had 4-18 migraine attacks of moderate to severe 
intensity per month in the 3 months prior to the Screening Visit, and at 
least 6 migraine days and no more than 18 headache days during the
28-day Observation Period which will be documented in the eDiary.
Upon completion of the Screening visit, subjects will be provided an
electronic diary (eDiary) to document each day of the 28-day 
Observation Period if a migraine occurred and the migraine intensity.  
Subjects will record the standard of care migraine treatment received
on a paper diary and female subjects will record their menstrual period
information on a paper log. After completing the 28-day Observation 
Period, the subject will return to the clinic with both diaries for the 
Baseline Visit. 
Subjects will have blood drawn for baseline lab profiles at the
Pre-Randomization Lab Visit; this visit must occur within 96 hours (4 
days) of the Baseline Visit. Sites are encouraged to complete this visit 
within 96 hours (4 days) of the Baseline Visit, however, if scheduling 


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challenges arise, site staff may use an additional +2 day window for 
this visit to occur within 144 hours (or 4 days, +2 days). Subjects will 
then return for the Baseline (Randomization) Visit.  
At the Baseline Visit, eligibility for continued participation in the study 
will be assessed before randomization occurs and before study 
medication is dispensed.  Subjects will be instructed that they must 
take one tablet of blinded study drug every other calendar day. If 
subjects have a migraine during the double-blind phase of the study, if 
needed, they may treat the migraine with their standard of care 
medication and continue to take study medication on their regular 
schedule (scheduled dosing days only).
At the completion of the 12-week double-blind, treatment phase, 
subjects will be evaluated for entry into the 52-week open-label,
extension phase following laboratory results within acceptable ranges
per protocol (Table 2).  During the open-label, extension phase, 
subjects will be instructed that they must take one tablet of study 
medication every other calendar day.  If subjects have a migraine on a 
day that they are not scheduled to dose with study drug, they may take 
one tablet of rimegepant on that calendar day to treat a migraine.  
Therefore, during the open-label, extension phase, subjects can take a 
maximum of one tablet of study drug per calendar day for this 52-week 
period.
Subjects are required to record their migraine occurrence and severity 
and all study medication doses in the eDiary. Subjects are also required 
to record the rescue medication taken on a paper diary and female 
subjects will record their menstrual period information on a paper log. 
Subjects will also use the eDiary to complete the Preference of 
Medication (PoM) and the Satisfaction with Medication (SM) scales at 
specified study timepoints.
At select study visits, subjects will complete or will be administered 
the Migraine-Specific Quality-of-Life Questionnaire v 2.1 (MSQ v 
2.1), the Migraine Disability Assessment (MIDAS), Clinical Global 
Impression – change (CGI-c) scale, and the Sheehan Suicidality 
Tracking Scale (S-STS) on paper forms.
Additional assessments and visit schedule are outlined in the
procedural table in Section 4.3.  Procedures include study personnel 
review of the eDiary and paper diary with the subject, assessment of 
study medication compliance, monitoring of tolerability and safety 
(including vital signs, laboratory tests, and electrocardiography).  


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Study visits will occur at Screening (Enrollment), Pre-Randomization 
Lab Visit which should occur within 96 hours (+48 hours) of the 
Baseline Visit, Baseline (Randomization), Week 2, Week 4, Week 8, 
and Week 12.  At the completion of the 12-week double-blind,
treatment phase, subjects will be evaluated for entry into the 52-week 
open-label, extension phase following laboratory results within 
acceptable ranges per protocol (Table 2). Visits occur at Week 14, 16, 
20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 / End of Treatment (EOT).  
Subjects will return to the study site at the end of Week 64 for the End 
of Treatment (EOT) Visit. There is a Follow-up Visit 14 days after the 
EOT Visit and 8 weeks after the EOT visit for assessment of LFTs.  
Subjects who do not complete the Double-blind, Treatment Phase 
and/or do not enter or complete the Open-label, Extension Phase 
should complete the End of Treatment Visit, the 2-Week Follow-up 
Safety Visit, and the 8-Week Follow-up Safety Visit.
To closely monitor for potential drug induced liver injury, guidance on 
reporting potential drug-induced liver injury (DILI) events is provided 
in the protocol. Lab results that meet predefined LFT abnormality 
criteria as potential DILI events should be reported as a serious adverse 
event (SAE). See Section 8.1.5 Potential Drug Induced Liver Injury 
(DILI).
Primary 
Endpoint: 
Change from baseline (observation period) in the mean number of
migraine days per month in the last four weeks (Weeks 9 to 12) of the 
double-blind treatment phase.
Secondary 
Endpoints:
Achievement of at least a 50% reduction from baseline in the mean 
number of moderate to severe migraine days per month in the last 4 
weeks of the double-blind treatment phase.
Change from baseline in the mean number of migraine days per month
over the entire double-blind treatment phase (Weeks 1 to 12).
The mean number of rescue medication days per month in the last 4 
weeks of the double-blind treatment phase.  Rescue medications 
include the rescue medications defined in this protocol (please refer to 
Section 5.5)
Change from baseline in the mean number of migraine days per month 
in the first 4 weeks (Weeks 1 through 4) of the double-blind treatment 
phase.


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The frequency of unique subjects with adverse events, serious adverse 
events, adverse events leading to discontinuation and clinically 
significant laboratory test abnormalities from case report forms and 
clinical laboratory evaluations. 
The frequency of unique subjects with AST or ALT elevations > 3x 
ULN, concurrently with bilirubin elevations > 2x ULN.
The frequency of unique subjects with hepatic-related adverse events 
and hepatic-related adverse events leading to treatment discontinuation 
from case report forms. 
The mean change from baseline in the MSQ role function - restrictive 
domain score at Week 12 of the double-blind treatment phase.
The mean change from baseline in MIDAS total score at Week 12 of 
the double-blind treatment phase.


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STUDY SCHEMATIC
Up to 12 weeks of double-blind treatment with every other day
dosing, followed by up to 52 weeks of open-label treatment with at least
every other day dosing
Start taking O-L  Medication 
or Subject to Return Study 
Medication 
Screen-
ing Visit 
Baseline 
Visit 
(Random-
ization)
12 week Double-blind 
Treatment Period 
End of 
Double-
blind 
Phase  
(Week 
12)/ 
Screening 
for Open-
label 
Phase or 
Early D/C 
Visit
Follow-
up Visits: 
14 days 
(+/- 2 
days)  
and 8
weeks (-2 
days to   
+14 days)
from EOT 
or Early 
D/C Visit
Up to 76 Weeks
Dispense and start 
taking study 
medication 
Stop Taking Study 
Double-blind 
Medication 
Rimegepant 
75 mg  EOD
Dosing
Placebo  
EOD
Dosing
Pre-
Rand 
Lab Visit 
for 
Double-
blind 
Phase: 
within 
96 hours
(+48 
hours)
of 
Baseline
28-Day Observation 
Period: Screening Visit to 
Baseline Visit
Contact 
Subject:  
Inform  
subject of 
eligibility 
to start 
dosing 
with study 
medication 
or 
ineligibility 
for open-
label phase  
52 week 
Open-label  
(O-L) 
Treatment 
Period 
Rimegepant 
75 mg  EOD
Dosing
/
k
\
 >
/
1


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TABLE OF CONTENTS
1
INTRODUCTION AND RATIONALE ..........................................................................23
1.1
BACKGROUND..........................................................................................................23
1.2
CGRP’S ROLE IN MIGRAINE.................................................................................23
1.3
PRODUCT DEVELOPMENT BACKGROUND.......................................................24
1.3.1
CLINICAL ADVERSE EVENT PROFILE .........................................................24
1.4
STUDY RATIONALE.................................................................................................24
1.4.1
STUDY DESIGN RATIONALE ...........................................................................25
1.4.2
DOSE SELECTION ..............................................................................................25
1.5
RESEARCH HYPOTHESIS.......................................................................................25
2
STUDY OBJECTIVES ....................................................................................................26
2.1
PRIMARY ...................................................................................................................26
2.2
SECONDARY..............................................................................................................26
3
STUDY ENDPOINTS ......................................................................................................29
3.1
PRIMARY ...................................................................................................................29
3.2
SECONDARY..............................................................................................................29
3.3
MEASURES OF INTEREST......................................................................................29
3.4
DEFINITION OF MIGRAINE DAYS .......................................................................30
3.5
DEFINITION OF HEADACHE DAYS......................................................................30
4
STUDY PLAN ..................................................................................................................31
4.1
STUDY DESIGN AND DURATION..........................................................................31
4.2
STUDY SCHEMATIC ................................................................................................33
4.3
SCHEDULE OF ASSESSMENTS..............................................................................34
4.3.1
SCREENING VISIT / OBSERVATION PERIOD (28 DAYS)............................42
4.3.1.1
PRE-RANDOMIZATION (LABORATORY) VISIT ....................................42
4.3.2
RANDOMIZED, DOUBLE-BLIND TREATMENT PHASE (12 WEEKS) .......43
4.3.3
OPEN-LABEL EXTENSION PHASE (52 WEEKS) ...........................................43
4.3.4
END OF TREATMENT (WEEK 64)....................................................................44
4.3.5
2-WEEK FOLLOW UP SAFETY VISIT .............................................................45
4.3.6
8-WEEK FOLLOW UP SAFETY VISIT .............................................................45
4.4
POST STUDY ACCESS TO THERAPY (IF APPLICABLE) ..................................45
5
POPULATION.................................................................................................................46
5.1
NUMBER OF SUBJECTS..........................................................................................46
5.2
INCLUSION CRITERIA............................................................................................46
5.3
EXCLUSION CRITERIA...........................................................................................47
5.4
PROHIBITED CONCOMITANT MEDICATION ...................................................52
5.5
PROPHYLACTIC AND RESCUE MEDICATIONS................................................53
5.6
WOMEN OF CHILDBEARING POTENTIAL.........................................................55
5.7
OTHER RESTRICTIONS AND PRECAUTIONS (IF APPLICABLE)...................55
5.8
DEVIATION FROM INCLUSION/EXCLUSION CRITERIA AND STUDY 
PROCEDURES ...........................................................................................................55


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6
STUDY CONDUCT AND DESCRIPTION OF STUDY PROCEDURES ....................56
6.1
STUDY MATERIALS.................................................................................................56
6.2
SAFETY ASSESSMENTS ..........................................................................................57
6.2.1
VITAL SIGNS AND PHYSICAL MEASUREMENTS (HEIGHT AND 
WEIGHT) ..............................................................................................................57
6.2.2
ELECTROCARDIOGRAM (ECG)......................................................................57
6.2.3
PHYSICAL EXAM................................................................................................57
6.2.4
LABORATORY ASSESSMENTS........................................................................58
6.2.4.1
SAFETY LABORATORY TESTING.............................................................58
6.2.4.2
PREGNANCY TESTING................................................................................58
6.2.5
SHEEHAN SUICIDALITY TRACKING SCALE...............................................59
6.3
EFFICACY ASSESSMENTS......................................................................................59
6.4
OTHER ASSESSMENTS ...........................................................................................59
6.4.1
MIGRAINE-SPECIFIC QUALITY-OF-LIFE QUESTIONNAIRE V 2.1 .........59
6.4.4
MIGRAINE DISABILITY ASSESSMENT (MIDAS) QUESTIONNAIRE........60
6.5
EARLY DISCONTINUATION FROM THE STUDY...............................................60
7
STUDY DRUG MANAGEMENT ...................................................................................62
7.1
DESCRIPTION OF STUDY DRUG...........................................................................62
7.1.1
INVESTIGATIONAL PRODUCT .......................................................................62
7.1.2
NON-INVESTIGATIONAL PRODUCT..............................................................62
7.1.3
PACKAGING, SHIPMENT AND STORAGE.....................................................62
7.2
DOSE AND ADMINISTRATION ..............................................................................63
7.2.1
METHOD OF ASSIGNING SUBJECT IDENTIFICATION..............................63
7.2.2
SELECTION AND TIMING OF DOSE AND ADMINISTRATION..................63
7.2.3
DOSE MODIFICATION.......................................................................................64
7.2.4
DOSE INTERRUPTIONS.....................................................................................64
7.3
BLINDING AND UNBLINDING ...............................................................................64
7.4
TREATMENT COMPLIANCE .................................................................................64
7.5
DESTRUCTION AND RETURN OF STUDY DRUG...............................................65
8
ADVERSE EVENTS........................................................................................................66
8.1
SERIOUS ADVERSE EVENT ...................................................................................66
8.1.1
DEFINITION OF SERIOUS ADVERSE EVENT (SAE) ....................................66
8.1.2
COLLECTION AND REPORTING SERIOUS ADVERSE EVENTS...............68
8.1.3
OVERDOSE...........................................................................................................69
8.1.4
PREGNANCY........................................................................................................70
8.1.5
POTENTIAL DRUG INDUCED LIVER INJURY (DILI)..................................70
8.2
NON-SERIOUS ADVERSE EVENTS........................................................................71
8.2.1
COLLECTION AND REPORTING OF NON-SERIOUS ADVERSE 
EVENTS.................................................................................................................71
8.2.2
LABORATORY TEST ABNORMALITIES........................................................71
9
STATISTICS....................................................................................................................72


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9.1
GENERAL PROCEDURES .......................................................................................72
9.2
POPULATIONS FOR ANALYSIS.............................................................................72
9.3
SAMPLE SIZE ............................................................................................................73
9.4
PRIMARY ENDPOINT ..............................................................................................73
9.5
SECONDARY ENDPOINT(S)....................................................................................73
9.6
MULTIPLICITY CORRECTION .............................................................................74
9.7
DEMOGRAPHIC AND BASELINE CHARACTERISTICS....................................75
9.8
SCHEDULE OF ANALYSES.....................................................................................75
10 ETHICS AND RESPONSIBILITIES..............................................................................76
10.1
GOOD CLINICAL PRACTICE.................................................................................76
10.2
DATA AND SAFETY MONITORING COMMITTEE ............................................76
10.3
INFORMED CONSENT.............................................................................................76
10.4
CASE REPORT FORMS............................................................................................78
10.5
RECORDS MANAGEMENT AND RETENTION....................................................78
10.6
SOURCE DOCUMENTATION .................................................................................79
10.7
STUDY FILES AND RECORD RETENTION..........................................................79
11 AMENDMENTS ..............................................................................................................80
12 STUDY REPORT AND PUBLICATIONS.....................................................................81
13 STUDY DISCONTINUATION .......................................................................................82
14 CONFIDENTIALITY......................................................................................................83
15 APPENDICES..................................................................................................................84
15.1
APPENDIX 1 - NAMES OF STUDY PERSONNEL .................................................84
15.2
APPENDIX 2 – INHIBITORS AND INDUCERS OF CYP3A4 OR CYP2C9 (NOT 
ALL-INCLUSIVE) ......................................................................................................85
15.3
APPENDIX 3 – DEFINITION OF MIGRAINE DAYS.............................................87
15.4
APPENDIX 4 – CATEGORIES OF MIGRAINE PREVENTION 
MEDICATIONS..........................................................................................................89
16 REFERENCES.................................................................................................................90


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LIST OF TABLES
Table 1.
Schedule of Assessments – Double-Blind Treatment Phase9, 10 ......................34
Table 2.
Schedule of Assessments – Open-label Extension Phase Including End of 
Treatment (EOT)10 & Follow-up Visits...........................................................38
LIST OF FIGURES
Figure 1.
Up to 12 Weeks of Double-blind Treatment with Every Other Day Dosing, 
Followed by Up To 52 Weeks of Open-label Treatment with at Least Every 
Other Day (EOD) Dosing.................................................................................33


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LIST OF ABBREVIATIONS
AE
Adverse Event
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
AUC
Area Under the Curve
bid
Twice Daily
BP
Blood Pressure
BUN
Blood Urea Nitrogen
Cmax
Maximum Plasma Concentration
CONMED
Concomitant Medication
CRF
CRPS
Case Report Form
Complex Regional Pain Syndrome
CTCAE
Common Terminology Criteria for Adverse Events
CV
Coefficient of Variation
DILI
Drug-Induced Liver Injury
DSMC
Data and Safety Monitoring Committee
DSM-V
Diagnostic and Statistical manual of Mental Disorders Fifth edition
ECG
EDC
EOD
Electrocardiogram
Electronic Data Capture
Every Other Day
FAS
Full analysis set
FSH
Follicle Stimulating Hormone


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GCP
Good Clinical Practice
HIV
Human Immunodeficiency Virus
HR
Heart Rate
ICF
Informed Consent Form
IB
Investigator’s Brochure
ICH
International Conference on Harmonization
ICF
Informed Consent Form
IEC
Independent Ethics Committee
HIS
International Headache Society
INR
International Normalized Ratio
IRB
Institutional Review Board
IV
Intravenous
IWRS
Interactive Web Response System
kBq
Kilobecquerel
kg
Kilogram
L
Liters
LFTs
Liver Function Tests
MBq
MDZ
Megabecquerel
Midazolam
mg
Milligram
MIDAS
Migraine Disability Assessment
MSQ
Migraine-Specific Quality-of-Life Questionnaire 


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min
Minute
mmHg
Millimeters Mercury
NOEL
No Observed Effect Level
NOAEL
O-L
No Observed Adverse Event Level
Open-label
PK
Pharmacokinetic
PO
By Mouth, Orally
QD
Once Daily
QTc
Interval between Q-wave and T-wave in the cardiac cycle
SAE
Serious Adverse Event
S-SST
Sheehan Suicidality Tracking scale
ULN
Upper Limit of Normal
WBC
White Blood Cell
WHO
World Health Organization
WOCBP
Women of Childbearing Potential


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1
INTRODUCTION AND RATIONALE
1.1
Background
Migraine is a common and debilitating neurological disorder that affects approximately 15% of 
the adult population. It is characterized by moderate-to-severe episodic unilateral pulsating 
headaches that last for 4 to 72 hours. Typical characteristics of the headache are unilateral 
location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, 
and association with nausea and/or photophobia and phonophobia.1 BHV-3000 (rimegepant) is a 
calcitonin gene-related peptide (CGRP) receptor antagonist in development for the acute 
treatment of migraine. The CGRP receptor is located within pain-signaling pathways, 
intracranial arteries and mast cells and its activation is thought to play a causal role in migraine 
pathophysiology. For example, research and clinical studies have shown: serum levels of CGRP 
are elevated during migraine attacks, infusion of intravenous CGRP produces persistent pain in 
migraine sufferers and non-migraine sufferers, and treatment with anti-migraine drugs normalize 
CGRP levels. Additionally, multiple clinical studies show that small molecule CGRP receptor 
antagonists, which inhibit the binding of endogenous CGRP to CGRP receptors, are effective in 
aborting migraine attacks. Treatment with a CGRP receptor antagonist is believed to relieve 
migraine through the possible mechanisms of 1) blocking neurogenic inflammation, 2)
decreasing artery dilation, and 3) inhibiting pain transmission. There is widespread agreement 
that this new approach avoids the cardiovascular effects produced by active vasoconstriction 
associated with the current standard triptan therapy (non-selective 5-HT1B/1D agonists (e.g., 
sumatriptan [Imitrex™])).
1.2
CGRP’s Role in Migraine
The CGRP receptor is located within pain-signaling pathways, intracranial arteries and mast cells 
and its activation is thought to play a causal role in migraine pathophysiology. For example, 
research and clinical studies have shown: serum levels of CGRP are elevated during migraine 
attacks, infusion of intravenous CGRP produces persistent pain in migraine sufferers and non-
migraine sufferers, and treatment with anti-migraine drugs normalize CGRP levels. Additionally, 
multiple clinical studies show that small molecule CGRP receptor antagonists, which inhibit the 
binding of endogenous CGRP to CGRP receptors, are effective in aborting migraine attacks.
Treatment with a CGRP receptor antagonist is believed to relieve migraine through the following 
possible mechanisms:

Blocking Neurogenic Inflammation: Binding of CGRP receptor antagonists to CGRP 
receptors located on mast cells would inhibit inflammation caused by trigeminal nerve 
release of CGRP onto mast cells within the tough outer covering of the brain, or the 
meninges.

Decreasing Artery Dilation: By blocking the CGRP receptors located in smooth muscle 
cells within vessel walls, CGRP receptor antagonists would inhibit the pathologic dilation 
of intracranial arteries without the unwanted effect of active vasoconstriction.


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
Inhibiting Pain Transmission: Binding of CGRP receptor antagonists to CGRP 
receptors would suppress the transmission of pain by inhibiting the central relay of pain 
signals from the trigeminal nerve to the caudal trigeminal nucleus.
1.3
Product Development Background
Details of the clinical and preclinical studies are provided in the most current Investigator 
Brochure. A summary of the relevant data to the study are presented below. 
1.3.1
Clinical Adverse Event Profile  
Rimegepant appears to be generally safe and well tolerated in humans when given as single oral 
doses up to the maximum dose of 1500 mg and multiple oral doses up to the maximum daily 
dose of 600 mg for 14 days. The ongoing BHV3000-201 study is a Phase 2/3, 52-week, open-
label, safety study with rimegepant 75 mg that is designed to enroll approximately 2000 subjects
to receive rimegepant up to once daily. Please refer to the Investigators Brochure for a summary 
of the clinical safety profile. 
The primary identified AE of interest is potential change in liver function tests. Investigators 
must carefully monitor routine liver function tests (ALT, AST, total bilirubin, and ALP) and 
potentially liver related symptoms and signs. Clinicians should  also monitor changes in 
hematology and other laboratory measures. Please refer to the current Investigators Brochure for 
further information regarding the clinical safety profile of rimegepant.
1.4
Study Rationale
The demonstrated efficacy of rimegepant in the three pivotal Phase 3 registrational trials in the 
acute treatment of migraine and the safety profile observed to date in the Phase 2/3 BHV3000-
201 long-term open-label safety study with up to daily dosing for as long as 1 year suggest that 
rimegepant may have an important role in the treatment of migraine.
This study is being conducted to evaluate the efficacy, safety, and tolerability of rimegepant for 
the prevention of migraine. It will also further define the safety profile of rimegepant
administration for as long as 64 weeks. Approximately 800 subjects will dose with blinded study 
drug at least every other day for a period of approximately 12 weeks, followed by an additional 
52 weeks with open-label rimegepant with scheduled dosing every other day as well.  During the 
open-label portion of the study, on days without scheduled rimegepant dosing, subjects may take 
up to 1 tablet of rimegepant per calendar day as needed for acute treatment of migraine.


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1.4.1
Study Design Rationale
This is a 12-week multicenter, randomized, double-blind, placebo controlled evaluation of the 
safety and efficacy of rimegepant 75 mg tablet taken every other day for the prevention of 
migraine with a 52-week open-label extension phase. Up to approximately 800 subjects will be 
randomized and assigned treatment in the double-blind phase of the study; it is estimated that 
approximately 675 subjects will enter the open-label phase of the study. During the double-blind 
phase, subjects will be instructed that they must take one tablet of blinded study drug every other 
calendar day. If subjects have a migraine during the double-blind phase of the study, if needed, 
they may treat the migraine with their standard of care medication and continue to take study 
medication on their regular schedule (scheduled dosing days only).
During the open-label phase of the study, subjects will be required to take one tablet of 
rimegepant every other calendar day.  However, if subjects have a migraine on a day that they 
are not scheduled to dose with rimegepant, they may take 1 tablet of rimegepant on that calendar
day to treat the migraine. Dosing with more than 1 tablet of study medication per calendar day is 
not permitted. Therefore, subjects can take a maximum of one tablet of study drug per calendar 
day for the 52 weeks of the open-label phase.
The study will randomize approximately 800 subjects and it is expected that approximately 675 
subjects will enter the open-label phase of the study. During the double-blind phase, the subjects 
will be randomized in a 1:1 ratio to the rimegepant or placebo treatment groups, stratified by
current use of prophylactic migraine medications (yes or no).
1.4.2
Dose Selection 
The Phase 2b dose-ranging study CN170003 established that rimegepant 75 mg is the minimum 
effective dose for the acute treatment of migraine. The three Phase 3 studies BHV3000-301, 
BHV3000-302, and BHV3000-303 confirmed this efficacy using the current registrational 
endpoints for acute treatment of migraine. In addition, several CGRP antagonists have been 
shown to be effective for the prevention of migraine.  This observation and the flat dose-response 
with rimegepant and other CGRP receptor antagonists suggest that rimegepant 75 mg every other 
day (EOD) may be an effective dose for the prevention of migraine.  The pharmacokinetic 
profile of rimegepant supports the dosing schedule of this protocol with up to daily dosing.
1.5
Research Hypothesis
Rimegepant is safe and effective treatment for the prevention of migraine.


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2
STUDY OBJECTIVES
2.1
Primary

To compare the efficacy of rimegepant to placebo as a preventive treatment for migraine, as 
measured by the reduction from baseline in the mean number of migraine days per month in 
the last four weeks of the double-blind treatment phase.  (A month is defined as 4 weeks for 
the purpose of this protocol). 
2.2
Secondary

To compare the efficacy of rimegepant to placebo on the proportion of subjects that have at 
least a 50% reduction from baseline in the mean number of moderate to severe migraine days 
per month in the last 4 weeks of the double-blind treatment phase.  

To compare the efficacy of rimegepant to placebo on the reduction from baseline in the mean 
number of migraine days per month over the entire course of the double-blind treatment 
phase.

To compare the frequency of use of rescue medications between the rimegepant and placebo 
in the last 4 weeks of the double-blind treatment phase.

To compare the efficacy of rimegepant to placebo on the reduction from baseline in the mean 
number of migraine days per month in the first 4 weeks of the double-blind treatment phase.

To evaluate the safety and tolerability of rimegepant.

To evaluate the frequency of ALT or AST > 3x ULN with concurrent elevations in bilirubin 
> 2x ULN in subjects treated with rimegepant.

To evaluate the frequency of hepatic-related adverse events and the frequency of hepatic-
related treatment discontinuations in subjects treated with rimegepant.

To compare the change from baseline in the Migraine-Specific Quality-of-Life Questionnaire 
v 2.1 (MSQ) role function - restrictive domain score at Week 12 of the double-blind 
treatment phase between rimegepant and placebo.

To compare the change from baseline in the Migraine Disability Assessment (MIDAS) total 
score at Week 12 of the double-blind treatment phase between rimegepant and placebo.


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3
STUDY ENDPOINTS 
3.1
Primary

Change from baseline (observation period) in the mean number of migraine days per month
in the last 4 weeks (Weeks 9 through 12) of the double-blind treatment phase.
3.2
Secondary

Achievement of at least a 50% reduction from baseline in the mean number of moderate to 
severe migraine days per month in the last 4 weeks of the double-blind treatment phase.

Change from baseline in the mean number of migraine days per month over the entire 
double-blind treatment phase (Weeks 1 to 12).

The mean number of rescue medication days per month in the last 4 weeks of the double-
blind treatment phase.  Rescue medications allowed in the 2 phases of this study are specified 
in Protocol Section 5.5.

Change from baseline in the mean number of migraine days per month in the first 4 weeks 
(Weeks 1 through 4) of the double-blind treatment phase.

The frequency of unique subjects with adverse events, serious adverse events, adverse events 
leading to discontinuation and clinically significant laboratory test abnormalities, from case 
report forms and clinical laboratory evaluations. 

The frequency of unique subjects with of AST or ALT elevations > 3x ULN, concurrently 
with bilirubin elevations > 2x ULN. 

The frequency of unique subjects with hepatic-related adverse events and hepatic-related 
adverse events leading to treatment discontinuation from case report forms. 

The mean change from baseline in the MSQ role function - restrictive domain score at Week 
12 of the double-blind treatment phase.

The mean change from baseline in the MIDAS total score at Week 12 of the double-blind 
treatment phase.
3.3
Measures of Interest
Not Applicable


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3.4
Definition of Migraine Days
A Migraine Day is defined as any calendar day which the subject 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
During the double-blind, treatment phase, if the subject takes a migraine-specific medication (i.e.
triptan or ergotamine) during aura or to treat a 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 open-label, 
extension phase. Dosing with study medication on non-scheduled dosing days is not permitted 
during the double-blind, treatment phase.
A moderate to severe migraine day is a migraine day with a migraine reported with moderate or 
severe pain intensity.
For the full definition of Migraine Days, please refer to Section 15.3 Appendix 3.
3.5
Definition of Headache Days
A Headache Day is any calendar day in which the subject experiences a qualified headache 
(initial onset, continuation, or recurrence of the headache). A qualified headache is defined as:

A qualified migraine headache (including an aura-only event that is treated with acute 
migraine-specific medication), or

A qualified non-migraine headache, which is a headache that lasts ≥ 30 minutes and is not a 
qualified migraine headache, or

A headache of any duration for which acute headache treatment is administered.


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4
STUDY PLAN
4.1
Study Design and Duration
This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy 
and safety of rimegepant in migraine prevention with an open-label extension phase.   
The Screening phase includes a screening visit and a 28-day Observation Period. For subjects to 
be eligible for the study, they must have reported having had 4-18 migraine attacks of moderate 
to severe intensity per month in the 3 months prior to the Screening Visit, and at least 6 migraine 
days and no more than 18 headache days during the 28-day Observation Period which will be 
documented in the eDiary.
Upon the completion of the screening visit, subjects will be provided an electronic diary (eDiary)
to document each day of the 28-day Observation Period if a migraine occurred, the migraine 
intensity and if the migraine was treated. Subjects will record the standard of care migraine 
treatment received on a paper diary and female subjects will record their menstrual period
information on a paper log. After completing the 28-day Observation Period, the subject will 
return to the clinic with both diaries for the Baseline Visit. 
Subjects will have blood drawn for baseline lab profiles at the Pre-Randomization Lab Visit; this 
visit must occur within 96 hours (4 days) of the Baseline Visit.  Sites are encouraged to complete 
this visit within 96 hours (4 days) of the Baseline Visit, however, if scheduling challenges arise, 
site staff may use an additional +2 day window for this visit to occur within 144 hours (or 4 
days, +2 days).  Subjects will then return for the Baseline (Randomization) Visit.  
At the Baseline Visit, eligibility for continued participation in the study will be assessed before 
randomization occurs and study medication will be dispensed. Subjects will be instructed that 
they must take one tablet of blinded study drug every other calendar day. If subjects have a 
migraine during the double-blind phase of the study, if needed, they may treat the migraine with 
their standard of care medication and continue to take study medication on their regular schedule 
(scheduled dosing days only).
At the completion of the 12-week double-blind phase, subjects may be entered into the 52-week 
open-label phase following laboratory test results within acceptable ranges per protocol (Table 
2).  During the open-label, extension phase, subjects will be instructed that they must take one 
tablet of study medication every other calendar day.  If subjects have a migraine on a day that 
they are not scheduled to dose with study drug, they may take 1 tablet of rimegepant on that 
calendar day to treat a migraine.  During the open-label, extension phase, subjects can take a 
maximum of one tablet of study drug per calendar day for this 52-week period.
Subjects are required to record their migraine occurrence and severity and all study medication 
doses in the eDiary. Subjects are also required to record the rescue medication taken on a paper 
diary and female subjects will record their menstrual period information on a paper log. 


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At select study visits, subjects will complete or will be administered the Migraine-Specific
Quality-of-Life Questionnaire v 2.1 (MSQ v 2.1), the Migraine Disability Assessment (MIDAS), 
, and the Sheehan Suicidality Tracking Scale 
(S-STS) on paper forms. 
Additional assessments and visit schedule are outlined in the procedural table in Section 4.3. 
Procedures include study personnel review of the eDiary and paper diary with the subject, 
assessment of study medication compliance, monitoring of tolerability and safety (including vital 
signs, laboratory tests, and electrocardiography).  
Study visits will occur at Screening (Enrollment), Pre-Randomization Lab Visit which must 
occur within 96 hours (+48 hours) of the Baseline Visit, Baseline (Randomization), Week 2, 
Week 4, Week 8, and Week 12.  At the completion of the 12-week double-blind phase, Subjects
may enter into the 52-week open-label phase if they continue to meet study entry criteria and
laboratory test results are acceptable per protocol (See Exclusion Criterion 8 in Section 5.3)
(Table 2). Visits occur at Week 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 / End of 
Treatment (EOT).  Subjects will return to the study site at the end of Week 64 for the End of 
Treatment (EOT) Visit. There is a Follow-up Visit 14 days after the EOT Visit and 8 weeks after 
the EOT visit for assessment of LFTs.  Subjects who do not complete the Double-blind, 
Treatment Phase and/or do not enter or complete the Open-label, Extension Phase should 
complete the End of Treatment Visit, the 2-Week Follow-up Safety Visit, and the 8-Week
Follow-up Safety Visit.
To closely monitor for potential drug induced liver injury, guidance on reporting potential drug-
induced liver injury (DILI) events is provided in the protocol. Lab results that meet predefined 
LFT abnormality criteria as DILI should be reported as a serious adverse event (SAE). See 
Section 8.1.5, Potential Drug Induced Liver Injury (DILI).


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4.2
Study Schematic
Figure 1.
Up to 12 Weeks of Double-blind Treatment with Every Other Day Dosing, Followed by Up To 52
Weeks of Open-label Treatment with at Least Every Other Day (EOD) Dosing
Screening 
Visit 
Baseline 
Visit 
(Random-
ization)
12 week Double-blind 
Treatment Period 
End of 
Double-
blind 
Phase  
(Week 
12)/ 
Screening 
for Open-
label 
Phase or 
Early D/C 
Visit
Follow-
up Visits: 
14 days 
(+/- 2 
days)  
and 8 
weeks (-2 
days to + 
14 days)
from EOT 
or Early 
D/C Visit
Up to 76 Weeks
Dispense and start 
taking study 
medication 
Stop Taking Study 
Double-blind 
Medication 
Rimegepant 
75 mg  EOD
Dosing
Placebo  
EOD
Dosing
Pre-
Rand 
Lab Visit 
for 
Double-
blind 
Phase: 
within 
96 hours
(+48 
hours) of 
Baseline
28-Day Observation 
Period: Screening Visit to 
Baseline Visit
Contact 
Subject:  
Inform  
subject of 
eligibility to 
start 
dosing with 
study 
medication 
or 
ineligibility 
for open-
label phase  
52 week 
Open-label  
(O-L) 
Treatment 
Period 
Start taking O-L  Medication 
or Subject to Return Study 
Medication 
Rimegepant 
75 mg  EOD
Dosing
_
_
/
‘
\
 >
/
1
_
12


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4.3
Schedule of Assessments
Table 1.
Schedule of Assessments – Double-Blind Treatment Phase9, 10
Procedure
Screening 
Visit
Observation 
Period10
(28 days, + 3
days)
Pre-Randomization 
Laboratory Visit: must 
occur within 96 hours of
Baseline (Randomization)
Visit11
Baseline 
(Randomization) 
Visit (Day 1)
Week 2   
(Day 14 +/-
2 days)
Week 4
(Day 28     
+3 days)
Weeks 8 (Day 
56) and 12
(Day 84)
(all visits + 3 
days)
Eligibility Assessments
Informed Consent
X
 
X
Inclusion/Exclusion Criteria
X
X
Medical History
X
Migraine History 
(signs/symptoms/prior 
treatment/frequency/intensity)
X
Rescue Medication paper diary, 
Concomitant Medication paper 
diary and Menstrual Period 
paper log (female subjects)1
X
X
X
X
X
X
X
Randomize subject / IWRS2
X
Safety Assessments
Physical Examination
X
X
X
X
Vital Signs / Physical 
Measurements3
X
X
X
X


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Procedure
Screening 
Visit
Observation 
Period10
(28 days, + 3
days)
Pre-Randomization 
Laboratory Visit: must 
occur within 96 hours of
Baseline (Randomization)
Visit11
Baseline 
(Randomization) 
Visit (Day 1)
Week 2   
(Day 14 +/-
2 days)
Week 4
(Day 28     
+3 days)
Weeks 8 (Day 
56) and 12
(Day 84)
(all visits + 3 
days)
Clinical Safety Laboratory 
Testing
X
X
X
X
Liver Function Test (LFTs)
X
X
X
X
X
X
Lipid Panel
X
ECG
X
X
X
Urinalysis
X
Urine Drug Screen for drugs of 
abuse
X
FSH, if applicable, to determine 
WOCBP status
X
Pregnancy Test
X (urine)
X (serum)
X (urine)
X (urine)
X (urine)
AE, SAE, and Concomitant 
Procedure assessment4
X
X
X
X
X
X
Sheehan Suicidality Tracking 
Scale
X
X
X
X
X
Clinical Drug Supplies / Study 
Supplies
Dispense Study Medication5
X
X
X
Administer study medication6
X
X
X
Electronic Diary (eDiary) 
dispensed
X


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Procedure
Screening 
Visit
Observation 
Period10
(28 days, + 3
days)
Pre-Randomization 
Laboratory Visit: must 
occur within 96 hours of
Baseline (Randomization)
Visit11
Baseline 
(Randomization) 
Visit (Day 1)
Week 2   
(Day 14 +/-
2 days)
Week 4
(Day 28     
+3 days)
Weeks 8 (Day 
56) and 12
(Day 84)
(all visits + 3 
days)
Enter use of study medication in 
eDiary
X
X
X
X
Return unused study medication 
to site for compliance check
X
X
X
eDiary returned / reviewed for 
completness7
X
X
X
X
X
X
Other Assessments
Daily report of migraine 
occurrence and severity 
reported by subject in eDiary8
X
X
X
X
X
X
Migraine-Specific Quality-of-
Life Questionnaire (MSQ) v 2.1
X
X (week 12 
only)
 
 
 
 
 
Migraine Disability Assessment 
(MIDAS)
X
X (week 12 
only)
1 Concomitant medications, including prophylactic and standard of care migraine medications, taken during Observation Period and rescue medication taken 
during the Treatment Phase should be recorded in the subject’s paper diary and reviewed by study personnel at each visit. Female subjects will also record 
menstrual period information on the paper diary which should be reviewed by study personnel at each visit.
2 The actual baseline visit date should be used for IWRS enrollment date and eligibility date.


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3 Height measured at Screening Visit only.  Weight, body temperature, respiratory rate, blood pressure, and heart rate will be collected at all timepoints where 
indicated.  Sitting arterial systolic and diastolic blood pressure and radial artery pulse rate will be measured.
4 SAEs, AEs, and Concomitant Procedures must be reported after subject signs informed consent.  SAEs should be reported from signing of consent through the 
8-week Follow up Safety Visit.  Non-serious AEs should be reported from signing of consent through 2-Week Follow up Safety Visit. 
5 Subjects should finish a bottle of study medication before starting a new bottle.  Study drug will be dispensed at monthly (every 4 weeks) study visits, as
needed.  Unscheduled visits to dispense study medication may be scheduled as needed.  At the Week 12 Visit, the open-label study medication will be dispensed 
and subjects will be instructed not to begin taking rimegepant until confirmation from site staff pending lab results.
6 Subjects must take their study medication every other day, regardless of whether or not they have a migraine.  Subjects must report each tablet they take in the 
eDiary.  Doses are not required to be taken in the office on days of a study visit, however dosing requirements and compliance should be discussed with subjects 
at all visits.  
7 The Observation Period to determine eligibility is 28 days +3 days. The “+3” days window is included for scheduling purposes only.  Subjects with less than 24 
completed eDiary reports during the Observation Period will not be considered for participation due to non-compliance with the eDiary.  Subjects in the Double-
blind, Treatment phase who demonstrate poor compliance will be discussed with the Sponsor and corrective training will be completed by the site with the 
subject.  
8 The electronic subject diary (eDiary) will be dispensed at the Screening Visit, after all Screening Procedures are completed.  The subject will be trained on the 
use of the eDiary.  The subject will use the eDiary every day during the Observation Period and Treatment Phase to report migraine occurrence, migraine severity 
and if the subject treated the migraine.
9 Subjects who do not complete the Double-blind, Treatment Phase or do not enter the Open-label, Extension Phase should complete the End of Treatment Visit 
and 2-Week and 8-Week Follow-up Safety Visits.
10 While on-study, all visit windows are used for scheduling purposes and all efforts should be made to return subjects to the 28-day schedule if scheduling 
changes are made at any previous visit(s).
11 The duration between the Pre-Randomization Lab Visit and the Randomization Visit is 4 days.  The “+2” days window is included for scheduling purposes 
only. Every effort should be made to collect the Pre-Randomization Lab Visit samples as close to, and within, the 4 days prior to the Randomization Visit as 
possible. However, for scheduling convenience, this window may be up to 6 days (between the Pre-Randomization Lab Visit and the Randomization Visit).


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Table 2.
Schedule of Assessments – Open-label Extension Phase Including End of Treatment (EOT)10 & 
Follow-up Visits
Procedure
Phone visit to 
confirm eligibility 
based on laboratory 
criteria1
Week 14 
(Day 98 ± 3
days)
Week 16 (Day 
112) and 20 
(Day 140)
(±3 days)
Visits every 4 
weeks Week 24
(Day 168) to Week 
64 (Day 448) / 
EOT     (±3 days)
2-Week Follow-
up Safety Visit
(14 days after 
EOT visit ± 2 
days)
8-Week Follow-
up Safety Visit
(8 weeks (-2 
days  to +14 
days) after EOT 
visit)
Confirm Week 12 Laboratory Results
X
Rescue Medication paper diary, 
Concomitant Medication paper diary 
and Menstrual Period paper log 
(female subjects)2
X
X
X
X3
X (Concomitant 
Medication 
paper diary only)
3
Safety Assessments
Physical Examinations
X (Week 16 
only)
X (Week 24 and 64 
/ EOT only)
Vital Signs / Physical Measurements4
X
X
X
Clinical Safety Laboratory Testing
X (Week 16 
only)
X (Week 24, 48, 
and 64 / EOT only)
Liver function tests (LFTs)
X
X
X
X
X
Lipid Panel
X (Week 24 and 64 
/ EOT only)
ECG
X (Week 16 
only)
X (Week 24, 48,
and 64 / EOT only)
X
Urinalysis
X (Week 64 / EOT 
only)
Pregnancy Test
X (urine)
X (urine)
X (urine)
X (serum)


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Procedure
Phone visit to 
confirm eligibility 
based on laboratory 
criteria1
Week 14 
(Day 98 ± 3
days)
Week 16 (Day 
112) and 20 
(Day 140)
(±3 days)
Visits every 4 
weeks Week 24
(Day 168) to Week 
64 (Day 448) / 
EOT     (±3 days)
2-Week Follow-
up Safety Visit
(14 days after 
EOT visit ± 2 
days)
8-Week Follow-
up Safety Visit
(8 weeks (-2 
days  to +14 
days) after EOT 
visit)
AE, SAE, and Concomitant Procedure
Assessment5
X
X
X
X
X5
Sheehan Suicidality Tracking Scale
X
X
X
X
Clinical Drug Supplies / Study 
Supplies
Dispense Study Medication 1, 6
X
X-all visits except 
Week 64 / EOT
Administer Study Medication7
X
X
X
Enter Use of Study Medication in 
eDiary
X
X
X
Return unused study medication to site 
for compliance check
X
X
X
eDiary returned/reviewed for 
completeness8
X
X
X
Other Assessments
Daily report of migraine occurrence 
and severity reported by subject in 
eDiary9
X
X
X
Migraine-Specific Quality-of-Life 
Questionnaire (MSQ) v 2.1
X (Weeks 24 and
64 only)


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Procedure
Phone visit to 
confirm eligibility 
based on laboratory 
criteria1
Week 14 
(Day 98 ± 3
days)
Week 16 (Day 
112) and 20 
(Day 140)
(±3 days)
Visits every 4 
weeks Week 24
(Day 168) to Week 
64 (Day 448) / 
EOT     (±3 days)
2-Week Follow-
up Safety Visit
(14 days after 
EOT visit ± 2 
days)
8-Week Follow-
up Safety Visit
(8 weeks (-2 
days  to +14 
days) after EOT 
visit)
Migraine Disability Assessment 
(MIDAS)
X (Weeks 24 and
64 only)
1 Study eligibility must be confirmed by Week 12 laboratory results prior to first dose of study medication, which is dispensed at the Week 12 visit. Sites must 
contact subject by phone to confirm study eligibility prior to subject taking first dose.
2 Concomitant medications, including prophylactic and rescue medications, taken during the Open-label, Extension Phase should be recorded in the subject’s 
paper diary and reviewed by study personnel at each visit. Female subjects will also record menstrual period information on the paper log which should be 
reviewed by study personnel at each visit.
3 Collect if treatment with concomitant medication is required for an AE or if concomitant medication is considered related to AE.
4 Weight, body temperature, respiratory rate, blood pressure, and heart rate will be collected at all timepoints where indicated.  Sitting arterial systolic and 
diastolic blood pressure and radial artery pulse rate will be measured.
5 SAEs, AEs, and Concomitant Procedures must be reported after subject signs informed consent.  SAEs should be reported from signing of consent through the 
8-week Follow up Safety Visit.  Non-serious AEs should be reported from signing of consent through 2-Week Follow up Safety Visit.
6 Subjects should finish a bottle of study medication before starting a new bottle.  Study drug will be dispensed at monthly (every 4 weeks) study visits, as 
needed.  Unscheduled visits to dispense study medication may be scheduled as needed.  Due to the COVID-19 Pandemic, study medication may be shipped to a 
subject, with up to an 8-week supply.  Proper documentation must be maintained in the subject’s source records including shipping vendor, tracking number, 
confirmation of receipt by subject, and all other relevant information.
7 Subjects must take their study medication every other day, regardless of whether or not they have a migraine.  During the open-label, extension phase only, if 
subjects have a migraine on a day that they are not scheduled to take a tablet of study medication, if needed, they may take a study medication tablet to treat a 
migraine on that calendar day.  Therefore, subjects can take a maximum of one (1) tablet of study medication per calendar day.  Subjects must report each tablet 
they take in the eDiary.  Doses are not required to be taken in the office on days of a study visit, however dosing requirements and compliance should be 
discussed with subjects at all visits.  
8 During the Open-Label, Extension Phase, subjects with 6 or more missed evening reports and 3 or more missed dosing entries per month for 2 months 
(sequential or non-sequential months) should be considered for discontinuation from the study for poor compliance, after discussion with Sponsor.  Month is 
defined as 4 weeks for the purpose of this protocol.


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9 The subject will be trained on the use of the eDiary.  The subject will use the eDiary every day during the Extension Phase to report migraine occurrence, 
migraine severity and if the subject treated the migraine.
10 While on-study, all visit windows are used for scheduling purposes and all efforts should be made to return subjects to the 28-day schedule if scheduling 
changes are made at any previous visit(s).  Due to the COVID-19 Pandemic, visits may be conducted remotely (ex: telephone, telemedicine) and must be 
documented within the source records as being conducted remotely.  All procedures not able to be completed due to a visit being conducted remotely must be 
reported as a protocol deviation and can be performed at the next visit, where appropriate to do so based on subject presentation.  In cases where a Week 64 / End 
of Treatment (EOT) visit occurs remotely in order to be completed during the protocol required window and due to the COVID-19 Pandemic, the subject should 
return to the site within the 8 Week Follow-up Safety Visit timeframe (8 weeks from last dose,  -2 to +14 days), to complete all procedures that weren’t able to be 
completed remotely.  Procedures completed at the Week 64 / EOT Remote Visit do not need to be repeated.


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4.3.1
Screening Visit / Observation Period (28 days)
Approximately 1500 subjects will be screened to randomize up to approximately 800 subjects to 
study medication (rimegepant or matching placebo). 
Before any study procedures are performed, subjects must sign informed consent. After informed 
consent, subjects will be enrolled in the IWRS system. The subject’s migraine history and 
medical history will be collected at the Screening Visit.  All subjects will continue to use their 
migraine prophylactic and/or standard of care medications during the 28-day Observation Period.  
Subjects will undergo all screening procedures as detailed in Table 1, after which they will be 
provided an eDiary to document each day during the 28-day Observation Period the occurrence
and severity of migraines. Subjects will also record all migraine standard of care treatments
taken during the Observation Period on a paper diary and female subjects will record their 
menstrual period information on a paper log. After completing the 28-day Observation Period, 
Subjects will return to the clinic, and both their eDiary and paper diary will be reviewed for 
completeness. 
During this period, and within 96 hours +48 hours (4 days +2 days) of the Randomization Visit, 
subjects must return to the study site for the Pre-Randomization Laboratory Visit.  See Table 1
for laboratory tests performed.  Subjects then return to the site for the Randomization Visit; if the 
subject is not eligible, the subject will be considered a Screen Failure.
If the subject meets inclusion/exclusion criteria, the subject may enter the double-blind treatment 
phase. 
4.3.1.1
Pre-Randomization (Laboratory) Visit
Within 96 hours +48 hours (4 days +2 days) of the Randomization Visit, subjects must return to 
the study site for the Pre-Randomization (Laboratory) Visit.  This visit occurs within the 
Observation Period.  Safety labs and a serum pregnancy test for WOCBP will be obtained and 
compliance with the eDiary will be assessed.  If the subject continues to meet study entry criteria 
and laboratory test results are acceptable per protocol, the subject will be randomized at the 
Baseline Visit into the double-blind treatment phase.  If the laboratory results are not acceptable 
per protocol, the subject is determined to be a Screen Failure and must return to the study site to 
return the eDiary. Repeat testing because of liver function test (LFT) abnormalities will not be 
permitted.


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4.3.2
Randomized, Double-blind Treatment Phase (12 weeks)
Once completing the Screening/Observational Period, subjects will return to the study site for the 
Baseline Visit. Subjects who continue to meet all inclusion/exclusion criteria and have been 
compliant with the eDiary may enter the Treatment Phase, pending review of additional 
laboratory test results; see Section 4.3.1.1. Because laboratory results from the Randomization 
(Baseline) Visit will be available after the subject may have been determined to be otherwise 
eligible for the study, had been randomized, and started treatment, there is the possibility that 
exclusionary laboratory results from the Randomization Visit may result in early discontinuation 
from the study.
Subjects will be instructed that they must take one tablet of study drug every other calendar day, 
regardless of whether they have a migraine on that day or not. If subjects have a migraine during 
the double-blind phase of the study, if needed, they may treat the migraine with their standard of 
care medication and continue to take study medication on their regular schedule (scheduled 
dosing days only).
The electronic subject diary will be completed by subjects to capture dosing of study medication 
and the frequency and severity of migraines during the Treatment Phase. 
Subjects will also use the eDiary to complete the Preference of Medication (PoM) and 
Satisfaction with Medication (SM) scales. The Migraine-Specific Quality-of-Life Questionnaire 
v 2.1 (MSQ), the Sheehan Suicidality Tracking Scale (S-STS), Migraine Assessment Disability 
(MIDAS) and Clinical Global Impression (CGI-c) will be completed, or administered by the 
investigator, on paper at specified study visits (Table 1)
Study visits will be approximately every two weeks during the first month and then every 4 
weeks, until Week 12 (Table 1). At each visit, the eDiary will be reviewed by site staff for 
completeness and compliance. Study medication compliance and concomitant medication use 
and menstrual period information (female subjects) will be reviewed (and compared to the 
eDiary and paper diary entries, where applicable) and subjects will be dispensed additional study 
medication as needed. Additional safety (including laboratory tests and ECGs) will be performed 
per the schedule outlined in Table 1. 
4.3.3
Open-label Extension Phase (52 weeks)
It is estimated that approximately 675 subjects will be entered into the open-label extension 
phase.
As indicated in Table 1, laboratory tests will be performed at the Week 12 visit (final visit of the 
double-blind treatment phase of the study).  Subjects who continue to meet all 
inclusion/exclusion criteria and have been compliant with the eDiary may enter the open-label 
extension phase, pending review of laboratory test results.  Subjects will be dispensed study 
medication and will be instructed that they cannot take study medication until laboratory results 


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confirm study eligibility.  Subjects may be contacted by telephone; an office study visit is not 
required.
Subjects will be instructed that they must take one tablet of study drug every other calendar day, 
regardless of whether they have a migraine on that day or not. If subjects in this group have a 
migraine on a day that they are not scheduled to dose with study medication, they may take 1 
study medication tablet on that calendar day to treat a migraine. Therefore, if needed, subjects 
can take a maximum of one tablet of study medication per calendar day for 52 weeks during the 
Open-label, Extension Phase.
The electronic subject diary will be completed by subjects to capture dosing of study medication 
and the frequency and severity of migraines during the Open-label, Extension Phase. 
Subjects will also use the eDiary to complete 
 and 
. The Migraine-Specific Quality-of-Life Questionnaire 
v 2.1 (MSQ), the Sheehan Suicidality Tracking Scale (S-STS), Migraine Assessment Disability 
(MIDAS) and 
 will be completed, or administered by the 
investigator, on paper at specified study visits (Table 2).
Study visits will be approximately every two weeks during the first month and then every 4 
weeks, until Week 64 (Table 2). At each visit, the eDiary will be reviewed by site staff for 
completeness and compliance. Study medication compliance and concomitant medication use 
and menstrual period information (female subjects) will be reviewed (and compared to the 
eDiary and paper diary entries, where applicable) and subjects will be dispensed additional study 
medication as needed. Additional safety (including laboratory tests and ECGs) will be performed 
per the schedule outlined in Table 2. 
Due to the COVID-19 Pandemic, visits may be conducted remotely (ex: telephone, telemedicine) 
and must be documented within the source records as being conducted remotely.  All procedures 
not able to be completed due to a visit being conducted remotely must be reported as a protocol 
deviation and can be performed at the next visit, where appropriate to do so based on subject 
presentation.  
4.3.4
End of Treatment (Week 64) 
Subjects will return to the study at the end of Week 64 (±3 days), or at end of treatment for early 
discontinuations, for review of the electronic diary, assessment of medication compliance, 
assessment of tolerability and safety (including vital signs, laboratory tests,  and  
electrocardiography) (Table 2). In cases where a Week 64 / End of Treatment (EOT) visit occurs
remotely in order to be completed during the protocol required window and due to the COVID-
19 Pandemic, the subject should return to the site within the 8 Week Follow-up Safety Visit 
timeframe (8 weeks from last dose,  -2 to +14 days), to complete all procedures that weren’t able 
to be completed remotely.  Procedures completed at the Week 64 / EOT Remote Visit do not 
need to be repeated.  Subjects must return the unused study medication and electronic subject
diary to the study site. Subjects who do not complete the Double-blind, Treatment Phase and/or 


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do not enter or complete the Open-label, Extension Phase should complete the End of Treatment 
Visit, 2-Week Follow up Safety Visit and 8-Week Follow up Safety Visit.
4.3.5
2-Week Follow up Safety Visit
Subjects will return to the study site 14 days after the Week 64/EOT Visit or early 
discontinuation visit, if applicable, (+/- 2 days) to collect laboratory tests, vital signs, 
electrocardiography, and assessment of AEs/ SAEs. Subjects will return the prophylactic and 
rescue medication paper diary and menstrual period (female subjects) paper logs which should 
be reviewed one final time by study staff.  Subjects must continue to track any concomitant 
medications and therefore must maintain the Concomitant Medication Use Log paper diary
through this visit.  Investigators should assess subjects for AEs consistent with drug dependency 
or withdrawal effects and report as appropriate (see Section 7.4).
4.3.6
8-Week Follow up Safety Visit
Subjects will return to the study site 8 weeks after the Week 64/EOT Visit or early 
discontinuation visit, if applicable (8 weeks (-2 days to +14 days)) to collect liver function tests
(LFTs), assessment of SAEs and to have a serum pregnancy test performed (WOCBP).  Subjects 
will return the Concomitant Medication Use Log paper diary for documenting concomitant 
medications.
4.4
Post Study Access to Therapy (if applicable) 
At the end of the study the sponsor will not continue to supply study drug to subjects or 
investigators. The investigator should ensure that the subject receives appropriate standard of 
care to treat the condition under study.


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5
POPULATION
5.1
Number of Subjects
It is anticipated that up to approximately 1500 subjects may be screened in order to randomize up 
to approximately 800 subjects to study medication (rimegepant or placebo). It is estimated that 
approximately 675 subjects will enter the open-label phase.
5.2
Inclusion Criteria
1. Signed Written Informed Consent
a) Written informed consent must be obtained from the subject 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.
b) Subjects must be able to read. 
2. Target Population
Subject 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 Edition2, 
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) Per subject report, 4-18 migraine attacks of moderate or severe intensity per month within 
the last 3 months prior to the Screening Visit (month is defined as 4 weeks for the 
purpose of this protocol)
d) 6 or more migraine days during Observation Period
e) Not more than 18 headache days during the Observation Period
f)
Ability to distinguish migraine attacks from tension/cluster headaches
g) Subjects on prophylactic migraine medication are permitted to remain on therapy if the 
dose has been stable for at least 3 months (12 weeks) prior to the Observation Period, and 
the dose is not expected to change during the course of the study.
i. Subjects may remain on one (1) medication with possible migraine-
prophylactic effects, excluding CGRP antagonists [biologic or small-
molecule], during the double-blind treatment phase.  


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ii. Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, 
is prohibited.
iii. Subjects who previously discontinued prophylactic migraine medication must 
have done so at least 90 days prior to the Screening Visit.
h) Subjects with contraindications for use of triptans may be included provided they meet all 
other study entry criteria
3. Age and Reproductive Status
a) Male and female subjects ≥ 18 years 
b) Women of childbearing potential (WOCBP) and non-sterile men must be using two 
acceptable methods of contraception to avoid pregnancy throughout the study in such a 
manner that the risk of pregnancy is minimized. See Section 5.6 for the definition of 
WOCBP. Males with vasectomy are considered surgically sterile provided the procedure 
occurred greater than 6 months (24 weeks) prior to study participation.
c) At the Baseline Visit, WOCBP must have a negative pregnancy test (minimum sensitivity 
25 IU/L or equivalent units of HCG) before dosing with study drug
4. Other Inclusion Criteria
a) No clinically significant abnormality identified on the medical or laboratory evaluation. 
A subject 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 exclusion criteria listed in Section 5 below)
5.3
Exclusion Criteria
1. Target Disease Exclusion
a) Subject has a history of basilar migraine or hemiplegic migraine
b) Subjects with headaches occurring 19 or more days per month (migraine or non-
migraine) in any of the 3 months prior to the Screening Visit.
2. Medical History and Concurrent Diseases
a) Subject history of HIV disease


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b) Subject history with current evidence of uncontrolled, unstable or recently diagnosed 
cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and 
cerebral ischemia. Subjects with myocardial infarction (MI), acute coronary syndrome 
(ACS), percutaneous coronary intervention (PCI), cardiac surgery, stroke or transient 
ischemic attack (TIA) during 6 months (24 weeks) prior to screening. 
c) Uncontrolled hypertension or uncontrolled diabetes (however, subjects can be included 
who have stable hypertension and/or diabetes for 3 months (12 weeks) prior to 
screening). Blood pressure greater than 150 mm Hg systolic or 100 mm Hg diastolic after 
10 minutes of rest is exclusionary.
d) Subjects with major depressive episode within the last 12 months, major depressive 
disorder or any anxiety disorder requiring more than 1 medication for each disorder. 
Medications to treat major depressive disorder or an anxiety disorder must have been at a 
stable dose for at least 3 months prior to the Screening visit.    
e) Active chronic pain syndromes (such as fibromyalgia, chronic pelvic pain, complex
regional pain syndrome [CRPS]).
f)
Subjects with other pain syndromes (including trigeminal neuralgia), psychiatric 
conditions, dementia, or significant neurological disorders (other than migraine) that, in 
the Investigator’s opinion, might interfere with study assessments
g) Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, 
Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has a disease that causes 
malabsorption 
h) Subject has a history or diagnosis of Gilbert’s Syndrome or any other active hepatic or 
biliary disorder
i)
The subject has a history or current evidence of any unstable medical conditions (e.g., 
history of congenital heart disease or arrhythmia, known or suspected infection, hepatitis 
B or C, or cancer) that, in the investigator’s opinion, would expose them to undue risk of 
a significant adverse event (AE) or interfere with assessments of safety or efficacy during 
the course of the trial
j)
History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months 
(48 weeks) or subjects who have met DSM-V criteria 9 for any significant substance use 
disorder within the past 12 months (48 weeks) from the date of the screening visit
k) History of use of opioid- or barbiturate- (e.g. butalbital) containing medication for 4 or 
more days per month during the 3 months (12 weeks) prior to Screening Visit. 


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l)
Subjects should be excluded if they have a positive drug screen for drugs of abuse that in 
the investigator’s judgment is medically significant, in that it would impact the safety of 
the subject or the interpretation of the study results. In addition:
i.
Detectable levels of cocaine, amphetamine and phencyclidine (PCP) in the drug 
screen are exclusionary. Subjects who have positive drug screen for 
amphetamines and who are on a prescribed amphetamine medication for an 
approved indication (e.g., ADHD) will be allowed into the study at the 
Investigator’s discretion.  The determination by the Investigator must be well 
documented in the subject’s source medical records.  The stimulant dose must be 
stable from 3 months (12 weeks) prior to baseline until the end of treatment visit 
occurs.
ii.
Detectable levels of marijuana in the drug screen are not exclusionary, if in the 
investigator’s documented opinion the subject does not meet DSM-V  criteria 9
for substance use disorder, and the positive test does not signal a clinical 
condition that would impact the safety of the subject or interpretation of the study 
results.
m) Hematologic or solid malignancy diagnosis within 5 years prior to screening. Subjects 
with a history of localized basal cell or squamous cell skin cancer are eligible for the 
study if they are cancer-free prior to the screening visit in this study.
n) Subject has current diagnosis of major depressive disorder requiring treatment with 
atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder
o) Body mass index > 33.0 kg/m2
p) History of gallstones or cholecystectomy 
3. Allergies and Adverse Drug Reactions
a) History of drug or other allergy which, in the opinion of the investigator, makes the 
subject unsuitable for participation in the study
4. Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable contraceptive method or 
abstinence to avoid pregnancy for the entire study period and for up to 8 weeks after last 
dose of study medication
b) Women who are pregnant or breastfeeding. 
c) Women with a positive pregnancy test at screening or prior to study drug administration


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5. ECG and Laboratory Test Findings
a) Estimated glomerular filtration rate (eGFR) according to the re-expressed abbreviated 
(four-variable) Modification of Diet in Renal Disease (MDRD) Study equation ≤ 40
ml/min/1.73m2
b) Corrected QT interval > 470 msec (QTc by method of Fridericia), at Screening
c) Left Bundle Branch block
d) Right Bundle Branch Block with a QRS duration ≥ 150 msec.
e) Intraventricular Conduction Defect with a QRS duration ≥ 150 msec.
f)
Serum bilirubin (Total, Direct or Indirect) > 1 x ULN (Only abnormal values of between 
1-1.5x ULN may be repeated once for assessment of eligibility during the screening 
period at the Screening Visit only. Abnormal bilirubin results obtained at the Pre-
Randomization Laboratory Visit may not be repeated.)
g) AST or ALT > 1 x ULN (Only abnormal values of between 1-1.5x ULN may be repeated 
once for assessment of eligibility during screening period at the Screening Visit only.
Abnormal AST or ALT results obtained at the Pre-Randomization Laboratory Visit may 
not be repeated.)
h) Neutrophil count ≤ 1000/μL (or equivalent)
i)
HbA1c > 6.5%
6. Prohibited Medications
a) History of use of analgesics (e.g. nonsteroidal anti-inflammatory drugs [NSAIDs] or 
acetaminophen) on ≥ 15 days per month during the 3 months (12 weeks) prior to the 
Screening Visit.
b) Subjects taking a prohibited medication (Refer to Section 5.4). 
7. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarilyincarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(e.g., infectious disease) illness
c) Non-compliance with or inability to complete eDiary during Observation Period. 
Subjects with less than 24 completed eDiary reports during the Observation Period will 
not be considered for participation due to non-compliance with the eDiary.  


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d) Exposure to non-biological investigational agents (other than rimegepant) within the 30 
days prior to Screening visit.
e) Exposure to biological investigational agents within the 90 days prior to Screening visit. 
f)
Score of > 0 on the Sheehan Suicidality Tracking Scale (See Section 6.2.5) for the period 
of 30 days prior to screening. 
g) Previous enrollment in any multiple dose BHV3000 (rimegepant) study, such as 
BHV3000-201, regardless of the number of doses taken. Subjects may be considered for 
BHV3000-305 if the subject participated in any of the following single dose studies: 
BHV3000-301, BHV3000-302, or BHV3000-303, but did not participate in any multiple 
dose rimegepant study. Note that subjects who were considered screen failures in a past 
BHV3000 study may be considered after discussion with the Sponsor and written 
approval is received.  Subjects who were considered screen failures from BHV3000-305 
may be considered for re-screening provided the ineligibility was due to one of the 
eligibility items adjusted in Amendment 03 (Protocol Version 04): exceeded number of 
headache days (previously greater than 13) or didn’t meet number eDiary entries during 
Observation Period (previously at least 26). Subjects may also be considered for re-
screening provided the ineligibility was due to the eligibility item adjusted in Amendment 
04 (Protocol Version 05): BMI less than 33.0 kg/m2 (previously BMI less than or equal to 
30kg/m2). Subjects who were considered screen failures from BHV3000-305 for other 
reasons should be discussed with the Sponsor and approval must be granted prior to 
considering for re-screening. Adequate documentation in source records must support the 
previously failed criteria.
h) Subjects are excluded if they have had no therapeutic response with > 2 of the 8
medication categories for prophylactic treatment of migraine listed in Appendix 4 after an 
adequate therapeutic trial.  Additional details can be found in Section 15.4 Appendix 4.
i)
Participation in any other investigational clinical trial while participating in this clinical 
trial. Subjects with an exclusionary match found in the CTS Database will be excluded.
j)
Past participation in a clinical trial within 30 days prior to the Screening Visit.  Note: 
Subjects who were considered screen failures within the last 30 days should not be 
considered as excluded.


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5.4
Prohibited Concomitant Medication 
The medications listed below are prohibited starting at the Baseline visit and during the course of 
this study or as specified. 
1. St. John’s Wort should not be taken 14 days prior to the Baseline visit and throughout the 
study.
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 (> 12 weeks)
4. Use of narcotic medication, such as opioids (e.g. morphine, codeine, oxycodone and
hydrocodone) or barbiturates is prohibited starting from 2 days prior to the Baseline Visit and 
throughout the study, including the 8-Week Follow-up Safety Visit. 
5. Use of acetaminophen or acetaminophen containing products for non-migraine indications 
after the Baseline visit is prohibited. Any use of acetaminophen or acetaminophen containing 
products for non-migraine indications during the Observation Period must be stopped at least 
2 days prior to baseline visit. Acetaminophen as a rescue medication as described in 
Section 5.5 is allowed during the Double-blind, Treatment phase. 
6. Use of triptans is prohibited during the Open-label Extension phase. 
7. The use of CGRP antagonists (biologic [e.g. Aimovig™ and Ajovy™] or small molecule) 
other than rimegepant is prohibited during the study.
8. Use of marijuana is prohibited during the study. 
9. Concomitant use of strong CYP3A4 inhibitors with rimegepant is prohibited during the 
double-blind, treatment phase of the study. If use of a strong CYP3A4 inhibitor is required
during the open-label, extension phase, such as use of 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 Section 15.2 Appendix2.
10. Concomitant use of strong CYP3A4 inducers with rimegepant is prohibited during the 
double-blind, treatment phase of the study. If use of a strong CYP3A4 inducer is required
during the open-label, extension phase, such as use of carbamazepine, phenytoin, or 
rifampin, dosing with rimegepant should be stopped and should not start again until 14 days 
after the last dose of the strong CYP3A4 inducer. Please see Section 15.2 Appendix 2.


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11. Concomitant use of CYP2C9 inhibitors with rimegepant is prohibited during the double-
blind, treatment phase of the study.  If use of a CYP2C9 inhibitor is required during the 
open-label, extension phase, such as fluconazole, amiodarone, or fluvoxamine, dosing with 
rimegepant should be stopped and should not start again until 14 days after the last dose of 
the CYP2C9 inhibitor.  
12. Concomitant use of CYP2C9 inducers with rimegepant is prohibited during the double-blind, 
treatment phase of the study.  If use of a CYP2C9 inducer is required during the open-label, 
extension phase, such as carbamazepine, aprepitant, or rifampin, dosing with rimegepant 
should be stopped and should not start again until 14 days after the last dose of the CYP2C9 
inducer.
13. Concomitant use of atypical antipsychotics such as Abilify (aripiprazole), Zyprexa
(olanzapine), Seroquel (quetiapine), Geodon (ziprasidone), or Risperdal (risperidone) or
Depakote/Depakene (valproic acid/valproate) is prohibited during the study.
14. Concomitant use of LAMICTAL (lamotrigine) is prohibited during the study.
15. Use of analgesics (e.g. nonsteroidal anti-inflammatory drugs [NSAIDs] or acetaminophen) 
on ≥15 days per month is prohibited during the study
16. Use of any investigational agent other than rimegepant from the Screening Visit through the 
8-Week Follow-up Safety Visit.
5.5
Prophylactic and Rescue Medications
Subjects may not use more than 1 of the following medications with possible migraine-
prophylactic effects if not otherwise prohibited by the protocol.  Doses must be stable within 3 
months (12 weeks) prior to the start of the Observation Period and throughout the study.  
Use of more than 1 of the following medications is prohibited within 3 months (12 weeks) prior 
to the start of the Observation Period and throughout the study.
Prophylactic migraine medications that are permitted during the study include:

Topiramate, gabapentin

Beta blockers (such as: atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, 
propranolol, timolol)

Tricyclic antidepressants (such as: amitriptyline, nortriptyline, protriptyline)

Venlafaxine, desvenlafaxine, duloxetine, milnacipran

Flunarizine, verapamil, lomerizine


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
Lisinopril, candesartan

Clonidine, guanfacine

Cyprohepatdine

Methysergide

Pizotifen

Feverfew, magnesium (≥ 600 mg/day), riboflavin (≥ 100 mg/day)

Botox®
The use of CGRP antagonists (biologic [e.g. Aimovig™, Ajovy™] or small molecule) other than 
rimegepant is prohibited during the study.
The use of triptan medications is prohibited during the Open-Label, Extension Phase of the 
study, but is allowed as rescue medication during the Double-blind, Treatment Phase.
During the Double-blind, Treatment Phase, subjects may use their permitted standard of care 
medication if needed for acute treatment of a migraine and record any medications taken on the 
appropriate paper diary. Permitted medications include the following rescue medications: 
triptans, aspirin, ibuprofen, baclofen, acetaminophen up to 1000 mg/day for a maximum of 2 
consecutive days at a time (this includes Excedrin Migraine), naprosyn (or any other type of non-
steroidal anti-inflammatory (NSAID)), antiemetics (e.g. metoclopramide or promethazine) or 
muscle relaxants for rescue during the study, with the exception that triptans are prohibited 
during the Open-Label Extension Phase. These are the only medications allowed for rescue. 
Subjects should continue taking study medication on scheduled dosing days.
If a subject takes a tablet of study drug and experiences a migraine later that day, after dosing 
with study drug for the day, the subject may take their rescue medication as described in this 
section of the protocol. During the double-blind, treatment phase, subjects are not allowed to 
take more than one tablet of study medication EVERY OTHER calendar day.  During the 
open-label, extension phase, subjects are required to dose every other day, but may take 1 
tablet of rimegepant on non-scheduled dosing days to treat a migraine.  Subjects are not
allowed to take more than one tablet of study medication per calendar day during the open-
label, extension phase.
Use of standard of care medication during Observation Period and use of rescue medication 
during the Treatment Phase, Extension Phase, and standard of care medication through to the 8-
Week Follow-up Safety Visit will be recorded by the subject on a paper diary and reported to the 
site.


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5.6
Women of Childbearing Potential
Women of childbearing potential (WOCBP) include any female who has experienced menarche 
and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal 
ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
1. Amenorrhea greater than or equal to 12 consecutive months (48 consecutive weeks) without 
another cause and a documented serum follicle stimulating hormone (FSH) level >
35mIU/mL at screening) or
2. Woman with irregular menstrual periods and a documented serum follicle stimulating 
hormone (FSH) level > 35mIU/mL (at screening) or
3. Woman on hormone replacement therapy (HRT) who no longer menstruate
NOTE: FSH level testing is not required for women greater than or equal to 62 years old with 
amenorrhea of greater than or equal to one year
NOTE: Women on HRT who still menstruate and women with irregular menses should be 
considered as WOCBP
Women of childbearing potential (WOCBP) and men must be using two acceptable methods of 
contraception to avoid pregnancy throughout the study and for up to 56 days after the last dose of 
investigational product in such a manner that risk of pregnancy is minimized. It is required that 
all WOCBP use two methods of contraception for the duration of the study (i.e. beginning at first 
treatment to 56 days after the last dose of study drug). The two methods should include one 
barrier method (ex. condom with spermicidal gel, intrauterine devices, cervical cap etc.) and one 
other method. The other method could include hormonal contraceptives or another barrier 
method.
WOCBP will complete a pregnancy test as outlined in Table 1 and Table 2.  If a WOCBP 
suspects that she might be pregnant, she should immediately contact the study doctor.
5.7
Other Restrictions and Precautions (if applicable)
Not Applicable
5.8
Deviation from Inclusion/Exclusion Criteria and Study Procedures
Any significant event that does not comply with the inclusion / exclusion criteria, study conduct, 
or study procedures will be documented as a deviation. Deviations will be documented and 
reported through the clinical monitoring of the trial. Deviations will be reported to the IRB/EC at 
the frequency required by your IRB/EC. There will be no protocol exceptions granted by the 
Sponsor for Inclusion/Exclusion criteria.


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6
STUDY CONDUCT AND DESCRIPTION OF STUDY PROCEDURES
6.1
Study Materials 
The following study materials will be provided at the study start:

Investigator File/Regulatory Binder

Pharmacy Binder

Drug Accountability Logs

Sample source documents, where applicable

Investigator Brochure

Interactive Web-based Response System (IWRS)

Electronic Case Report Form (eCRF) instructions

Electronic Diary: hand held electronic device (1 will be given to each subject)

Instructions for the eDiary device and access to the portal

Paper diary to record standard of care migraine medications and rescue medications

Paper diary to record menstrual period information (female subjects)

Laboratory Kits and Laboratory Manual

ECG Machine and Instructions

Serious Adverse Event (SAE) forms

Pregnancy Surveillance Forms

Sheehan Suicidality Tracking Scale (S-STS) forms

MIDAS forms

MSQ v 2.1 forms


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All sites will use an Electronic Data Capture (EDC) tool to submit study data to the CRO.
Electronic Case Report Forms (eCRFs) will be prepared for all data collection fields including
Serious Adverse Events (SAE) Reporting. SAE data (including queries) will be submitted to the 
CRO using eCRFs. 
The eDiary will be used daily to record all study medication dosing, rescue medication dosing
occurrences (i.e., with triptans, ergotamine, or other), select subject-rated scales, and migraine 
occurrence, characteristics, and severity. Any assessment completed by the subject in the eDiary
will be transferred from the site/subject to the vendor and from the vendor to the CRO and 
Sponsor. No additional source documents are required for scales and assessments completed by 
the subject on the eDiary.
Safety laboratory, plasma, and serum instructions for all specimens collected will be provided by 
a designated central laboratory. ECG equipment, supplies, instructions and training materials will 
be supplied by a centralized ECG vendor.
6.2
Safety Assessments
6.2.1
Vital Signs and Physical Measurements (Height and Weight)
Vital signs, body weight and height will be recorded at the scheduled visits as outlined in Table 1
and Table 2.
6.2.2
Electrocardiogram (ECG)
A standard 12-lead ECG will be recorded during the Screening Phase and at all scheduled visits 
as outlined in Table 1 and Table 2. A central ECG service will be utilized for reading all ECGs.  
The over read from the central ECG vendor should be used to determine eligibility for the study. 
The investigator will determine if any ECG abnormalities are clinically significant or not.
6.2.3
Physical Exam
Subjects will undergo a routine physical examination during the Screening Phase and at all 
scheduled visits as outlined in Table 1 and Table 2. Physical examinations to include 
examination of heart, abdomen and lungs, with review of any other system to be guided by 
symptoms.


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6.2.4
Laboratory Assessments
6.2.4.1
Safety Laboratory Testing
Blood and urine samples will be obtained as outlined in Table 1 and Table 2 for clinical 
laboratory evaluations. A central laboratory vendor will be utilized for this study and a 
laboratory manual will be provided to each site. If possible, subjects should be fasting for a 
minimum of 8 hours before laboratory tests. However, if a subject is not fasting at a given 
visit, the blood draw should still be performed, and the non-fasting status should be documented.
1. Clinical safety labs: 
Hematology: Hemoglobin, hematocrit, red blood cell count, white blood cell count with 
differential, and platelets;
Chemistry: Sodium, potassium, chloride, bicarbonate, calcium; glucose, HbA1c, BUN 
(urea), serum creatinine, uric acid, LDH, total protein, albumin, CPK (with local lab 
fractionation, if CK result is > 5.0 x ULN).
eGFR using the estimated MDRD formula (calculated at central lab);
2. LFTs: AST, ALT, Alkaline Phosphatase and Bilirubin (Total, Direct, Indirect).  Additional 
tests may be obtained to evaluate laboratory abnormalities and/or adverse events; please refer 
to the Laboratory manual.
3. Lipid panel: Cholesterol, LDL, HDL, triglycerides
4. Urinalysis: pH, specific gravity, ketones, nitrites, urobilinogen, leukocyte esterase, protein, 
glucose, and blood. If blood, protein or leukocytes are positive, reflex to microscopic
examination.
5. Urine Drug Screen: For drugs of abuse
6. FSH: For WOCBP at screening, to determine WOCBP status
Additional tests may be obtained to evaluate laboratory abnormalities and/or adverse 
events; please refer to the Laboratory Manual.
6.2.4.2
Pregnancy Testing
WOCBP will complete pregnancy tests (serum and / or urine) at specified study visits, prior to
taking study medication, and as outlined in Table 1.


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6.2.5
Sheehan Suicidality Tracking Scale  
The Sheehan STS (S-STS) is a prospective, subject-reported or clinician-administered rating 
scale that contains 16 questions to track both treatment-emergent suicidal ideation and 
behaviors.10,11 The S-STS will be completed on a paper form at the site. At the screening visit, 
the recall period for completing the S-STS is 30 days prior; at all other visits, the recall period 
for completing the S-STS is since the last visit. Any responses other than 0 must be immediately 
evaluated by the investigator. If the investigator determines that a subject is at risk of suicide or 
self-harm, appropriate measures to ensure the subject’s safety and obtain mental health 
evaluation must be implemented. In such circumstances, the subject must immediately 
be discontinued from the study. The event should be recorded as either an AE or SAE as 
determined by the investigator and reported within 24 hours to the Sponsor. Any subject with a 
response greater than 0 to any question, excluding Question 2, must be immediately discontinued 
from the study. Subjects with a response of 1 (“a little”) to Question 2 will be discontinued per 
the investigator’s assessment or if the response persists. Subjects with a response greater than 1 
on Question 2 will be discontinued from the study immediately.
6.3
Efficacy Assessments
The eDiary will be used daily to record rescue medication dosing occurrences (i.e., with triptans, 
ergotamine, or other), and migraine occurrence, characteristics, and severity during the 
observation period, double-blind treatment phase, and open-label extension phase.
Efficacy assessments will be derived from eDiary data, and will include the number of migraine 
days by severity (total; moderate or severe) per month, number of  rescue medication days per 
month, and MRM days per month, in each month by study period. 
6.4
Other Assessments
6.4.1
Migraine-Specific Quality-of-Life Questionnaire v 2.1
Impact of treatment on subject-reported quality of life will be assessed using the Migraine-
Specific Qualify-of-Life Questionnaire version 2.1 (MSQ v 2.1). The MSQ v 2.1 is a 14-item 
instrument that has been validated in 3 domains: role function - restrictive, role function -
preventive, and emotional function.12
 


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6.4.4
Migraine Disability Assessment (MIDAS) Questionnaire
The Migraine Disability Assessment (MIDAS) is a retrospective, subject-reported, 5-item 
questionnaire that measures headache-related disability as lost days due to headache from paid 
work or school, household work and non-work activities over a 3-month period. The MIDAS 
will be completed on a paper form at the site.13
 
 
6.5
Early Discontinuation from the Study
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Withdrawal of informed consent (subject’s decision to withdraw for any reason)

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject

Exclusionary laboratory abnormality identified on the Randomization / Baseline Laboratory 
Report.  

Pregnancy

Termination of the study by Biohaven Pharmaceuticals

Loss of ability to freely provide consent through imprisonment or involuntary incarceration 
for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Poor compliance with study procedures and visits, including poor completion compliance 
with evening reports in eDiary. 


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i.
Subjects with less than 24 completed eDiary reports during the Observation Period will 
not be considered for participation due to non-compliance with the eDiary.  
ii.
Subjects in the Double-blind, Treatment Phase will be monitored closely for 
compliance with the eDiary and may not be considered for the Open-label, Extension 
Phase based on PI and / or Sponsor discretion if compliance is low.  Subjects who 
demonstrate poor compliance will be discussed with the Sponsor and corrective 
training will be completed by the site with the subject.
iii.
During the Open-Label, Extension Phase, subjects with 6 or more missed evening 
reports in the eDiary and 3 or more missed dosing entries per month for 2 months 
(sequential or non-sequential months) should be considered for discontinuation from 
the study for poor compliance, after discussion with Sponsor. Month is defined as 4 
weeks for the purpose of this protocol.

Please see Section 6.2.5 for guidance on study discontinuation based on results from the S-
STS.
All subjects who discontinue or who do not enter the Open-label, Extension Phase should 
comply with protocol specified End of Treatment procedures as outlined in Table 2. The only 
exception to this requirement is when a subject withdraws consent for all study procedures or 
loses the ability to consent freely (i.e., is imprisoned or involuntarily incarcerated for the 
treatment of either a psychiatric or physical illness).
 
 
 
 
 
 
 
 


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7
STUDY DRUG MANAGEMENT
7.1
Description of Study Drug
7.1.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined as follows:
A pharmaceutical form of an active substance or placebo being tested or used as a reference in a 
clinical study, including products already with a marketing authorization but used or assembled 
(formulated or packaged) in a way different from the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, investigational product is rimegepant 75 mg tablet or matching placebo. 
7.1.2
Non-investigational Product
Other medications used as support or rescue medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be 
considered as non-investigational products.
In this protocol, non-investigational product(s) is/are: standard of care for acute and preventive 
treatment and rescue medication for migraine treatment.
7.1.3
Packaging, Shipment and Storage
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by the sponsor. 
Please see the Pharmacy Manual for specific conditions. If concerns regarding the quality or 
appearance of the study drug arise, do not dispense the study drug and contact the sponsor/CRO
immediately.


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7.2
Dose and Administration
7.2.1
Method of Assigning Subject Identification
Immediately after written informed consent is obtained and before performing any study-related 
procedures, the site staff must obtain a subject identification by adding a new subject in Rave. In 
this study, the Rave system will be utilized for obtaining subject identification and as the 
electronic data capture (EDC) system. Each subject will be assigned a unique sequential 4-digit 
subject number through Rave (0001, 0002, 0003, etc.). This subject number must not be reused 
for any other participant in the study. Subjects will maintain their subject number assigned at 
screening throughout the trial. 
At the Baseline Visit, eligible subjects will be randomized in a 1:1 ratio to the rimegepant or placebo 
treatment groups. The randomization will be stratified by the use of prophylactic migraine 
medications (yes or no). 
After confirming subject eligibility, registering a subject for Baseline (Randomization) will 
trigger a container number for the study medication. The study drug will be dispensed at baseline
and as needed at the study visits.
7.2.2
Selection and Timing of Dose and Administration
Study medication (rimegepant or matching placebo) will be assigned via the Rave system. There 
are no dose adjustments in this study and subjects will receive 30 tablets of rimegepant or 
placebo in a bottle. Subjects will be dispensed study medication at the Baseline Visit, and the 
subjects will be instructed that they must take one tablet every other calendar day, regardless of 
whether they have a migraine on that day or not.  This is the scheduled dosing regimen for the 
double-blind treatment phase and the open-label, extension phase.  
During the open-label, extension phase, subjects will receive open-label rimegepant.  Subjects 
will be instructed that they must take one tablet every other calendar day, regardless of whether 
they have a migraine on that day or not.  During the open-label, extension phase only, if a subject
has a migraine on a non-scheduled dosing day, they may take 1 tablet of rimegepant as acute 
treatment for their migraine, if needed, with a maximum of one tablet per calendar day. This 
regimen of scheduled dosing on every other calendar day and as needed rimegepant dosing 
should be followed for up to 52 weeks in the open-label, extension phase. Subjects can take a 
maximum of one tablet of study medication per calendar day for 52 weeks during the open-label, 
extension phase.
Dosing should occur around the same time every other day (EOD) for migraine prevention.  It is 
preferred that subjects dose every other day in the morning, however, it is more important that 
the subject consistently dose at approximately the same time every other day.  The time of 
dosing should be consistent throughout the study for the EOD dosing days.  If the subject has a 
migraine on a day when they already took study medication, the subject can take their rescue 
medication in accordance with protocol restrictions.  Subjects must be instructed that they 


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CANNOT take more than one tablet of study medication every other day during the double-
blind, treatment phase.  Subjects must be instructed to continue taking study medication every 
other calendar day during the open-label, extension phase.  As noted above, subjects may treat a 
migraine with study medication on a non-scheduled dosing day, but subjects must be instructed 
that during the open-label, extension phase, they CANNOT take more than 1 tablet of 
rimegepant per calendar day.  
7.2.3
Dose Modification
There will be no dose adjustments in this study.
7.2.4
Dose Interruptions
If a subject experiences an AE that requires interruption in study medication, the investigator 
should consult with the Sponsor medical monitor to evaluate the need for any additional tests 
prior to re-starting study medication. 
7.3
Blinding and Unblinding 
Blinding is critical to the integrity of this clinical study. However, in the event of a medical 
emergency or pregnancy in an individual subject, in which knowledge of the investigational 
product is critical to the subject’s management, the blind for that subject may be broken by the 
treating physician. 
Before breaking the blind of an individual subject’s treatment, the investigator should have 
determined that the information is necessary, (i.e., that it will alter the subject’s immediate 
management). In many cases, particularly when the emergency is clearly not investigational 
product related, the problem may be properly managed by assuming that the subject is receiving 
active product without the need for unblinding. 
In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt to 
preserve the blind is made.
7.4
Treatment Compliance
Responsible study personnel will dispense the study drug.  Subjects should finish a bottle of 
study medication before starting a new bottle. Accountability and compliance verification should 
be documented in the subject’s study records.  
Subjects must be counseled on the importance of taking the study drug as directed (see 
Section 7.2.2). Treatment compliance, review of study medication doses reported in the eDiary
and through review of returned study medication, should be assessed by site staff at each study 
visit. Discrepancies between doses reported in the eDiary, review of study medication and 
information provided by subject must be documented in the source record. Incorrect or missing 
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Data Clarification Record or a Medication Reconciliation Form. Investigators should inform
Subjects that involuntary termination from the study will occur in cases where non-compliance is 
identified. Study staff should contact a subject in between the monthly study visits if the subject
demonstrates non-compliance with the eDiary and document the contact in the source, to identify 
potential lost to follow up subjects as early as possible. 
Investigators must monitor subjects for possible cases of abuse of study medication (subjects
taking study drug for non-therapeutic purposes, e.g. for psychoactive effects such as high or 
euphoria). Investigators should also assess study drug accountability discrepancies (e.g. missing 
study medication, loss of drug, or non-compliance cases in which more study medication was 
used, as compared to expected). Investigators should obtain more information and explanation 
from subjects when there are study drug accountability discrepancies. See Section 8.1.1.
Cases of potential study medication abuse or overdose (including cases of non-compliance with 
study medication dosing instructions or subjects who discontinue treatment without returning 
study medication) should be documented in the source record and reported as an AE or SAE as 
appropriate. Dosing errors (e.g. accidentally taking 2 tablets in one calendar day) should be 
reported as deviations. 
7.5
Destruction and Return of Study Drug
If the study drug (those supplied by the sponsor or sourced by the investigator) are to be 
destroyed 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.  The unused study drugs can only be destroyed after being 
inspected and reconciled by the responsible Biohaven (BHV) Study monitor or the sponsor’s 
designee unless this is against institutional policy. 
All unused and/or partially used study drug may be destroyed on site providing the site has an 
applicable standard operating procedure on file.


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8
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
pre-existing medical condition in a subject or clinical investigation subject administered an 
investigational (medicinal) product and that does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding for example) symptom, or disease temporally associated with the 
use of the investigational product, whether or not considered relate to the investigational product. 
Adverse events can be spontaneously reported or elicited during an open-ended questioning, 
examination, or evaluation of a subject.  In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs.
There are two types of adverse events, Serious Adverse Events (SAE) and Non-Serious Adverse 
Events (AEs).
8.1
SERIOUS ADVERSE EVENT
8.1.1
Definition of Serious Adverse Event (SAE)
An SAE is any event that meets any of the following criteria at any dose:

Death

Life-threatening

Inpatient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

Congenital anomaly/birth defect in the offspring of a subject who received rimegepant

Other: Important medical events that may not result in death, be life-threatening, or require 
hospitalization, may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such events are (but not limited to):
o
Intensive treatment in an emergency room or at home for allergic bronchospasm
o
Blood dyscrasias or convulsions that do not result in inpatient hospitalization
o
Development of drug dependency or drug abuse
o
Potential drug induced liver injury (see Section 8.1.5)


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o
Abuse or Overdose of medication

Potential study medication abuse (including cases of excessive non-compliance with 
study medication dosing instructions or subjects who discontinue treatment without 
returning study medication) should be documented in the source record and reported 
as an AE or SAE as appropriate. Investigators must monitor subjects for possible 
cases of abuse of study medication (subjects taking study drug for non-therapeutic 
purposes, e.g. for psychoactive effects such as high or euphoria). Investigators should 
obtain more information and explanation from subjects when there are study drug 
accountability discrepancies

Potential study medication overdose is defined in Section 8.1.3
Definition of Terms
Mild: Is usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily living.
Moderate: Is usually alleviated with additional specific therapeutic intervention. The event 
interferes with usual activities of daily living, causing discomfort but poses no significant or 
permanent risk of harm to the subject.
Severe: Interrupts usual activities of daily living, significantly affects clinical status, or may 
require intensive therapeutic intervention.
Life threatening: An AE is life threatening if the subject was at immediate risk of death from the 
event as it occurred; i.e., it does not include a reaction that if it had occurred in a more serious 
form might have caused death. For example, drug induced hepatitis that resolved without 
evidence of hepatic failure would not be considered life threatening even though drug induced 
hepatitis can be fatal.
Hospitalization: AEs requiring hospitalization should be considered SAEs. Hospitalization for 
elective surgery or routine clinical procedures that are not the result of AE (e.g., elective surgery 
for a pre-existing condition that has not worsened) need not be considered AEs or SAEs. If 
anything untoward is reported during the procedure, that occurrence must be reported as an AE, 
either 'serious' or 'non-serious' according to the usual criteria.
In general, hospitalization signifies that the subject has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician's office or outpatient setting. When in doubt as to 
whether 'hospitalization' occurred or was necessary, the AE should be considered serious.
The following hospitalizations are not considered SAEs in Biohaven clinical studies (but may be 
considered non-serious AEs):


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1. A visit to the emergency room or other hospital department <24 hours that does not result in 
an admission (unless considered “important medical event” or event that is life threatening);
2. Elective surgery planned prior to signing consent;
3. Admissions as per protocol for a planned medical/surgical procedure;
4. Routine health assessment requiring admission (i.e., routine colonoscopy);
5. Admission encountered for another life circumstance that carries no bearing on health and 
requires no medical intervention (i.e., lack of housing, care-giver respite, family 
circumstances).
Disability/incapacitating: An AE is incapacitating or disabling if the experience results in a
substantial and/or permanent disruption of the subject's ability to carry out normal life functions.
8.1.2
Collection and Reporting Serious Adverse Events
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specific procedures.   All SAEs must be collected that occur during the observation
phase and up to and including the 8-Week Follow-up. The investigator should report any SAE 
occurring after this time period that is believed to be related to study drug or protocol-specific 
procedures.  
All SAEs should be followed to resolution or stabilization.
An SAE report should be completed for any event where doubt exists regarding its status of 
seriousness.  
If the investigator believes that an SAE is not related to the study drug, but is potentially related 
to the conditions of the study (such as a withdrawal of previous therapy or a complication related 
to study procedure), the relationship should be specified in the narrative section of the SAE 
Report Form. 
SAEs, whether related or not related to study drug, overdose (see Section 8.1.3), potential drug 
induced liver injury (see Section 8.1.5) and pregnancies (see Section 8.1.4) must be reported 
within 24 hours of the Investigator becoming aware of the event. For this study we will be 
capturing SAEs through electronic data capture (EDC) and on the SAE form.
The Investigator is responsible for reporting all SAEs and all Other Important Medical Events to 
 
 
 


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the Investigator, or designated staff, is responsible for entering the SAE information in the 
Electronic Data Capture (EDC) system (i.e.: event term, start stop dates, causality, severity).
Any serious adverse event must be reported immediately or no later than 24 hours after 
awareness of the event to 
 
 
If a form is unable to be submitted within 24 hours, the SAE may be reported by telephone via 
the Safety Hotline Number:
If only limited information is initially available, follow-up reports are required. If an ongoing 
SAE changes in its intensity or relationship to study drug or if new information becomes 
available, a follow-up SAE report should be sent within 24 hours of the Investigator becoming 
aware of the updated information using the same procedure used for the transmission of the 
initial SAE and the same event term should be used.
The minimum information required for an initial SAE report is:
Sender of report (Site number, Investigator name)
Subject identification (subject number)
Protocol number
SAE term (if an SAE is being reported)
8.1.3
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a
product that is considered both excessive and medically important.  
All occurrences of overdose (suspected or confirmed) must be communicated to Biohaven or a 
specified designee within 24 hours and be fully documented as an SAE. Details of any signs or 
symptoms and their management should be recorded including details of any treatments
administered.
Asymptomatic dosing errors (e.g. accidentally taking 2 tablets in one calendar day) should be 
reported as deviations.


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8.1.4
Pregnancy
If, following the baseline visit, it is subsequently discovered that a study subject 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 subject safety).  
Protocol-required procedures for the study discontinued and the follow-up must be performed on 
the subject 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 Biohaven (or designee) Medical Monitor of the 
event and complete the Pregnancy Form within 24 hours and in accordance with SAE reporting 
procedures as described in Section 8.1.2. The pregnancy should be reported using paper forms, 
which should be faxed to 
 
 
 
 
 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable offspring information must be reported on a Pregnancy Report 
Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
the sponsor.  Information on this pregnancy will be collected on the Pregnancy Report Form, as 
appropriate.   
8.1.5
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of the initial liver-related laboratory abnormalities 
should occur prior to the reporting of a potential DILI event.  All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs as per Section 8.1.2. 
Potential drug induced liver injury is defined as: 
1. ALT or AST elevation > 3 times the upper limit of normal (ULN)
AND
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum 
alkaline phosphatase)


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AND
3. No other immediately apparent possible causes of ALT or AST elevation and 
hyperbilirubinemia, including but not limited to, viral hepatitis, pre-existing chronic or 
acute liver disease, or the administration of other drug(s) known to be hepatotoxic. 
If any potential DILI is identified and meets the criteria above, the Biohaven Medical Monitor 
(or designee) should immediately be contacted for further instruction and whether the subject
must discontinue from the trial and appropriate follow up requirements. 
8.2
Non-serious Adverse Events
A non-serious adverse event is an AE not classified as serious. 
8.2.1
Collection and Reporting of Non-Serious Adverse Events
The collection of non-serious AE information should begin at the initiation of study drug through 
the 2-Week Follow up Safety Visit.    Non-serious AE information should also be collected from 
the start of a placebo lead-in phase or other observation period intended to establish a baseline 
status for a subject. 
Non-serious adverse events should be followed until conclusion or stabilization, or reported as 
SAEs if they become serious.   Follow-up is also required for non-serious AEs that cause 
interruption or discontinuation of study drug or those that are present at the end of study 
treatment. 
8.2.2
Laboratory Test Abnormalities
The following laboratory test abnormalities should be captured on the non-serious AE CRF page 
or SAE Report Form (paper or electronic) as appropriate:
1. Any laboratory test result that is clinically significant or meets the definition of an SAE;
2. Any laboratory abnormality that required the subject to have the study drug discontinued or 
interrupted;
3. Any laboratory abnormality that required the subject to receive specific corrective therapy.


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9
STATISTICS
Complete details on the statistical methods for this study may be found the Statistical Analysis 
Plan (SAP).
9.1
General Procedures
Categorical variables are tabulated with counts and percentages. Continuous variables are 
summarized with univariate statistics (e.g., n, mean, standard error, median, minimum and 
maximum).  
For the calculation of descriptive statistics of observed data, subjects must have a baseline value 
to be evaluable for endpoints based on values and changes from baseline over time.
Tabulations of the following endpoints present the number of unique subjects with an event: 
protocol deviations; interruptions of study therapy; non-study medications; adverse events; and 
laboratory abnormalities. Thus, for these endpoints, multiple occurrences of the same event are 
counted only once per subject.
9.2
Populations for Analysis
The set of enrolled subjects consists of all subjects who signed the informed consent form and 
were assigned a subject identification number.
The set of randomized subjects consists of enrolled subjects who were assigned a randomized 
treatment group and prophylactic migraine medication use stratum.
The full analysis set (FAS) includes all randomized subjects who received at least one dose of 
double-blind study medication (rimegepant or placebo). 
The efficacy analysis set is a subset of the FAS that includes subjects with at least 14 days of 
eDiary data in both the Observation Period and at least one 4-week interval during the double-
blind treatment phase. 
The safety analysis set consists of all enrolled subjects who received at least one dose of study 
medication (double-blind or open-label).   For the double-blind phase, subjects in safety analyses 
will be analyzed based on their randomized treatment so long as they receive at least one dose of 
their randomized treatment. Otherwise, subjects will be analyzed based on the actual treatment 
received.
The rimegepant safety analysis set includes enrolled subjects who received at least one dose of 
rimegepant (double-blind or open-label).


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9.3
Sample Size
With a sample size of roughly 800 subjects randomized, and 400 subjects per group, we expect 
roughly 370 subjects per group in the efficacy data set.  Assuming rimegepant provides roughly a 
1 day advantage over placebo on the primary endpoint, and a common standard deviation of 3.75 
days, then the study will have roughly 95% power on the primary endpoint.  The estimates for 
the change in migraine days per month and the standard deviation are consistent with publicly 
available information from another investigational oral CGRP antagonist for this indication.
9.4
Primary Endpoint
The change from baseline efficacy endpoint is analyzed using a generalized linear mixed effect 
model, that includes subject as a random effect, and has the baseline number of migraine days  
(i.e., during the Observation Period) as a covariate.  The model includes fixed effects for:
treatment group; stratification factor (use of prophylactic migraine medication); scheduled visit; 
and the visit by-treatment group interaction. Scheduled visits included in the model are 
nominally at 4, 8 and 12 weeks. Evaluation of migraine days per month is based on the data from 
the previous visit to the current visit (i.e., 4-week interval), and is prorated to account for missing 
migraine reports. A migraine days per month endpoint, prorated to 28 days, will be computed for 
subjects in the efficacy analysis set who provide at least 14 days of eDiary data during any 
reporting period (i.e., Observation Period or a 4-week interval during the double-blind treatment 
phase). The difference estimate (rimegepant - placebo), standard error, 95% confidence interval, 
and p-value will be reported for the last 4 weeks (Weeks 9 to 12) of the double-blind treatment 
phase.
9.5
Secondary Endpoint(s)
The number of subjects that experience at least a 50% reduction in the mean number of moderate 
or severe migraine days per month in the last 4 weeks of the double-blind treatment phase will be 
analyzed using a stratified Cochran-Mantel-Haenszel (CMH) test after the missing data are 
imputed as non-response.
The change from baseline in the mean number of migraine days per month over the entire 
double-blind treatment phase (Weeks 1 to 12) will be assessed with the same statistical model 
used to analyze the primary endpoint.
The use of rescue medications (mean number of days per month) in the last 4 weeks of the 
double-blind treatment phase will be assessed using a generalized linear mixed effects model that 
is similar in structure to that used for the primary analysis. Rescue medications are defined in 
Section 5.5.
The change from baseline in the mean number of migraine days per month in the first 4 weeks 
(Weeks 1 to 4) of the double-blind treatment phase will be assessed with the same statistical 
model used for to analyze the primary endpoint.


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The investigators will determine the severity of adverse events (AEs) and the relationship of AEs 
to study therapy. The investigators’ terms will be coded and grouped by system organ class using 
the latest version of the Medical Dictionary for Regulatory Activities (MedDRA) available to the 
analyst. AEs will be presented by system organ class and preferred term. If a subject had an 
adverse event with different severities over time, then only the worst severity will be reported.  
Tabulations will be made for the frequency of unique subjects with adverse events (by severity, 
by relationship to study drug, and overall), serious adverse events, adverse events leading to 
treatment discontinuation, hepatic-related adverse events (by severity, by relationship to study 
drug, and overall), and hepatic-related adverse events leading to treatment discontinuation from 
case report forms. 
The frequency of unique subjects with clinically significant laboratory test abnormalities will be 
tabulated based on Grade 3 - 4 clinical laboratory evaluations graded using the latest version of 
Common Terminology Criteria for Adverse Events (CTCAE). 
Other safety analyses will be described in the statistical analysis plan.
The frequency of unique subjects that have ALT or AST that exceed 3x the ULN concurrently 
(on the same laboratory test occasion) with total bilirubin that exceeds 2x the ULN will be 
tabulated and presented with descriptive statistics and exact confidence intervals. 
Safety endpoints will be assessed separately for the following phases and populations:

Double-blind treatment for the safety analysis set;

Rimegepant treatment (double-blind or open-label) for the rimegepant safety analysis set. 
The changes from baseline in MSQ role function - restrictive domain score and MIDAS total 
score at Week 12 will be analyzed using generalized linear models that include the baseline score 
as a covariate, and fixed effects for treatment group and stratification factor (use of prophylactic 
migraine medication). The Week 12 difference estimate (rimegepant - placebo), standard error, 
95% confidence interval, and p-value will be reported for each endpoint. 
9.6
Multiplicity Correction
Type 1 error is controlled through the use of hierarchical testing.  The significance of the primary 
endpoint is evaluated at the 0.05 level.  If the primary endpoint is significant, then the following 
secondary endpoints will be tested hierarchically in the following order, each at the 0.05 level:

proportion of subjects with a 50% reduction in the mean number of moderate or severe 
migraine days per month in the last 4 weeks of the double-blind treatment phase;

change from baseline in the mean number of migraine days per month over the entire 
course of the double-blind treatment phase; 


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
use of rescue medications (mean number of days per month) in the last 4 weeks of the 
double-blind treatment phase;

change from baseline in the mean number of migraine days per month in the first 4 weeks 
of the double-blind treatment phase;

change from baseline in MSQ role function - restrictive domain scores at Week 12 of the 
double-blind treatment phase;

change from baseline in MIDAS total score at Week 12 of the double-blind treatment 
phase. 
Thus, a secondary endpoint will be tested only if the preceding secondary endpoint in the 
hierarchy is determined to be significant.  Descriptive p-values will be provided for any non-
significant secondary endpoints and comparative exploratory endpoints.
9.7
Demographic and Baseline Characteristics
Tabulations of demographic and baseline characteristics are made for FAS subjects. Separate 
tabulations are made for subjects enrolled but not in FAS.
9.8
Schedule of Analyses
The data from this study may be locked and analyzed at any point after the last subject completes 
their last visit in the double-blind phase of the study, and adequate time has been allowed for 
follow-up.  Analyses of the data may be conducted after the double-blind phase, and at any point
in, or after, the open-label phase.


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10 ETHICS AND RESPONSIBILITIES
10.1
Good Clinical Practice
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP), 
Good Laboratory Practice (GLP) and all applicable regulations, including the Federal Food, 
Drug and Cosmetic Act, U.S. applicable Code of Federal Regulations (title 21), any Independent 
Ethics Committee (IEC) requirements relative to clinical studies. The study will also be 
conducted in compliance with the recommendations laid down in the most recent version of the 
Declaration of Helsinki, with the exception that registration of such Phase 1 trials in a publicly 
accessible database is not mandatory. 
This study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.   
All serious breaches must be reported to Biohaven (or designee) immediately.  A Serious breach 
is a breach of the conditions and principles of GCP in connection with the stud or protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
subjects of the study or the scientific value of the study. 
Study personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective task(s). 
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (e.g., loss of medical licensure, debarment).
10.2
Data and Safety Monitoring Committee
This study will not make use of a Data Safety Monitoring Committee (DMC). The study 
medication rimegepant has been tested and found to be well tolerated.  Safety will be closely 
monitored via oversight by the investigators, Sponsor and CRO/designee and an Institutional 
Review Board/Independent Ethics Committee.
10.3
Informed Consent
Investigators must ensure that subjects, or, in those situations where consent cannot be given by 
subjects, their legally acceptable representatives, are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they 
volunteer to participate. 
Biohaven (or designee) will provide the investigator with an appropriate (i.e., Global or Local) 
sample informed consent form which will include all elements required by ICH, GCP and 
applicable regulatory requirements.  The sample informed consent form will adhere to the ethical 
principles that have their origin in the Declaration of Helsinki.


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Before the potential subject has undergone any study-related screening procedures, the nature of 
the study and the potential risks associated with it will be explained to the subject, and the 
subject will be given an opportunity to ask questions to his or her satisfaction. After the 
questions are answered, but before proceeding further, the subject must read and sign a written 
informed consent form for study participation and CTS database participation. These signed 
informed consent forms will be reviewed and approved by an IRB/IEC, revisions to the protocol 
and informed consent form will be reviewed and approved by the IRB/IEC, a copy retained in 
the Study Master File, and the date and time the subject signed the form will be entered in his or 
her CRF. The subject will be provided with a copy of his or her signed and dated informed 
consent forms.  
If informed consent is initially given by a subject’s legal guardian or legally acceptable 
representative, and the subject subsequently becomes capable of making and communicating 
their informed consent during the study, then the consent must additionally be obtained from the 
subject. 
The informed consent form must also include a statement that Biohaven and its representatives 
and regulatory authorities may have direct access to subject records. 
The Investigators agree to provide the IEC with all appropriate documents, including a copy of 
the protocol/amendments, ICFs, advertising text (if any), Investigator’s brochure and any other 
written information provided to study subjects. The trial will not begin until the Investigators 
have obtained the IEC favorable written approvals for the above-mentioned study documents. A 
properly executed written ICF shall be read, signed, and dated by each subject prior to entering 
the trial or prior to performing any study procedure. The original signed and dated ICF will be 
kept at the Investigator site and a copy will be given to the subject. 
In the event that the protocol is amended, the revised protocol must be approved by the IEC prior 
to its implementation, unless the changes involve only logistical or administrative aspects of the 
trial. If a revised ICF is introduced during the study, each subject’s further consent must be 
obtained. The new version of the ICF must be approved by the IEC, prior to subsequently 
obtaining each subject’s consent. 
The Principal investigator and the Sponsor’s representative must sign the protocol and its 
amendments (if any) before initiating the study. 
It is the Sponsor’s responsibility to submit the protocol and its amendments (if any), and the 
ICFs to regulatory authorities when necessary.
The rights, safety, and well-being of study subjects are the most important considerations and 
should prevail over interests of science and society.


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10.4
Case Report Forms
An Investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation of each study subject. Data 
reported on the CRF that are derived from source documents must be consistent with the source 
documents or the discrepancies must be explained.
Electronic CRFs will be prepared for all data collections fields when electronic data capture 
(EDC) is being used.   
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s). 
The Investigator must retain a copy of the CRFs including records of changes and corrections.   
If EDC is being used, signatures will be obtained electronically and a copy of the electronic 
CRFs will be provided (or the data from the CRFs) for future reference.
10.5
Records Management and Retention
In accordance with the principles of GCP and GLP, the study may be inspected by regulatory 
authorities, the Sponsor and CRO. The Sponsor is entitled to access information about the status 
of the study and to review the original documents of the study.
The Investigator must retain all study records and source documents for the maximum required 
by the applicable regulations and guidelines, or institution procedures or for the period of time 
specified by the sponsor, whichever is longer.  The Investigator must contact the Sponsor prior to 
destroying any records associated with this study. 
Biohaven will notify the Investigators when the study files for this study are no longer needed. 
If the Investigator withdraws from the study (i.e., retirement, relocation), the records shall be 
transferred to a mutually agreed upon designee.  Notice of such transfer will be given in writing 
to Biohaven. 
It is the responsibility of the Investigator to ensure that the current disposition record of 
investigational product (those supplied by the sponsor) is maintained at each study site where the 
study drug is inventoried and dispensed.  Records or logs must comply with applicable 
regulations and guidelines and should include:
1. amount of study drug received and placed in storage area
2. label ID number or batch number or Kit number as specified for the protocol
3. amount dispensed to and returned from each subject
4. amount transferred to another area or site for dispensing or storage if applicable


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5. amount of drug lost or wasted
6. amount destroyed at the site, if applicable
7. amount returned to sponsor, if applicable
8. retain sampled for bioavailability/bioequivalence, if applicable
9. record of dates and initials of personnel responsible for IM dispensing and accountability  
10.6
Source Documentation
An Investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent for all subjects on study.  
If source documents are created to support the collection of study information, this must be 
retained with the other pertinent medical record for each subject for verification of data points.   
Unless otherwise instructed by the Sponsor or designee to enter data directly on the eCRF.
10.7
Study Files and Record Retention
The CRO will maintain adequate study records after completion or termination of study. After 
that period, the Sponsor will be contacted to determine whether the study records will be 
forwarded to the Sponsor, destroyed or kept at CRO or at another facility for a longer period of 
time at the Sponsor's expense.


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11 AMENDMENTS
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Biohaven. A protocol change intended to eliminate an apparent immediate hazard 
to subjects may be implemented immediately, provided the IRB/IEC is notified within 5 days.
Any permanent change to the protocol must be handled as a protocol amendment. The written 
amendment must be submitted to the IRB/IEC and the investigator must await approval before
implementing the changes. Biohaven will submit protocol amendments to the appropriate 
regulatory authorities for approval.
If in the judgment of the IRB/IEC, the investigator, and/or Biohaven, the amendment to the 
protocol substantially changes the study design and/or increases the potential risk to the subject 
and/or has an impact on the subject's involvement as a study participant, the currently approved 
written informed consent form will require similar modification. In such cases, informed consent 
will be renewed for subjects enrolled in the study before continued participation.


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12 STUDY REPORT AND PUBLICATIONS
Biohaven is responsible for preparing and providing the appropriate regulatory authorities with 
clinical study reports according to the applicable regulatory requirements.
The publication policy of Biohaven is discussed in the investigator's Clinical Research 
Agreement.


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13 STUDY DISCONTINUATION 
Both Biohaven and the Principal Investigator reserve the right to terminate the study at the 
investigator’s site at any time. Should this be necessary, Biohaven or a specified designee will 
inform the appropriate regulatory authorities of the termination of the study if needed and the 
reasons for its termination, and the Principal Investigator will inform the IRB/IEC of the same. 
In terminating the study, Biohaven and the Principal Investigator will assure that adequate 
consideration is given to the protection of the subjects’ interests.


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14 CONFIDENTIALITY
All information generated in this study is considered highly confidential and must not be 
disclosed to any person or entity not directly involved with the study unless prior written consent 
is gained from Biohaven. However, authorized regulatory officials, IRB/IEC personnel, 
Biohaven and its authorized representatives are allowed full access to the records.
Identification of subjects and eCRFs shall be by initials and subject numbers only. Only if 
required by law, the subject's full name may be made known to an authorized regulatory agency 
or other authorized official.


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15 APPENDICES
15.1
APPENDIX 1 - Names of Study Personnel


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15.2
Appendix 2 – Inhibitors and Inducers of CYP3A4 or CYP2C9 (Not all-
inclusive)
The following text presents some of the inhibitors and inducers of CYP3A or CYP2C9. This list 
should not be considered all-inclusive. Individual drug labels should be reviewed for specific 
information on propensity to inhibit or induce CYP450 enzymes for a specific compound. 
As described in the study protocol, concomitant use of strong CYP3A4 inhibitors is prohibited.
Strong CYP3A inhibitors
Boceprevir, cobicistat, conivaptan, danoprevir and ritonavir, elvitegravir and ritonavir, 
indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and 
ritonavir and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, 
telaprevir, tipranavir and ritonavir, troleandomycin, voriconazole, clarithromycin, 
nefazodone, nelfinavir 
The following medications and supplements are some of the strong inducers of CYP3A4. As 
described in the study protocol, concomitant use of strong CYP3A4 inducers is prohibited. 
Individual product labels should be reviewed for specific information on 
CYP3A inducers
Carbamazepine, phenytoin, rifampin, St. John’s wort
The following medications and medication combinations are some of the inhibitors of CYP2C9. 
As described in the study protocol, concomitant use of CYP2C9 inhibitors is prohibited. 
Individual drug labels should be reviewed for specific information on 
CYP2C9 inhibitors
amiodarone, felbamate, fluconazole, miconazole, piperine, diosmin, disulfiram, fluvastatin, 
fluvoxamine, voriconazole
The following medications and supplements are some of the inducers of CYP2C9. As described 
in the study protocol, concomitant use of CYP2C9 inducers is prohibited. Individual product 
labels should be reviewed for specific information on propensity to 
CYP2C9 inducers
aprepitant, carbamazepine, enzalutamide, rifampin, ritonavir
Resources: 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
onsLabeling/ucm093664.htm#table3-2
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
onsLabeling/ucm093664.htm#table3-3


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Hachad H, Ragueneau-Majlessi I, Levy RH. A useful tool for drug interaction evaluation: the 
University of Washington Metabolism and Transport Drug Interaction Database. Hum 
Genomics. 2010 Oct;5(1):61-72.
University of Washington Metabolism and Transport Drug Interaction Database accessible at 
https://www.druginteractioninfo.org/


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15.3
Appendix 3 – Definition of Migraine Days
Migraine Day: Any calendar day in which the subject 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 subject 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 open-
label, extension phase; dosing with study medication on non-scheduled dosing days is not 
permitted during the double-blind, treatment phase.
A moderate to severe migraine day is a migraine day with a migraine reported with moderate or 
severe pain intensity.
Headache Day: Any calendar day in which the subject experiences a qualified headache (initial 
onset, continuation, or recurrence of the headache). A qualified headache is defined as:

a qualified migraine headache (including an aura-only event that is treated with acute 
migraine-specific medication), or

a qualified non-migraine headache, which is a headache that lasts ≥ 30 minutes and is 
not a qualified migraine headache, or

a headache of any duration for which acute headache treatment is administered.


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Acute Migraine-specific Medication Treatment Day: Any calendar day during which the 
subject took a migraine-specific medication (i.e., study medication [open-label, extension phase 
only], triptan or ergotamine). The use of study medication on non-scheduled dosing days is only 
permitted during the open-label, extension phase; dosing with study medication on non-
scheduled dosing days is not permitted during the double-blind, treatment phase.
Monthly eDiary Data: Data collected by the eDiary based on the subject’s monthly
investigational product dosing schedule when at least 14 days of eDiary data are collected within 
that interval. Monthly frequency measurements will be prorated to 28-day equivalents.
Migraine Attack: An episode of any qualified migraine headache. The following rules will be
used to distinguish an attack of long duration from two attacks, or to distinguish between attacks 
and relapses:
a) A migraine attack that is interrupted by sleep, or temporarily remits, and then recurs 
within 48 hours (i.e., ≤ 48 hours between the start of the migraine attack to the time of 
the recurrence) will be considered as one attack and not two.
b) An attack treated successfully with medication but with relapse within 48 hours (i.e., 
≤ 48 hours between the start of the migraine attack to the time of the recurrence) will 
be considered as one attack.


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15.4
Appendix 4 – Categories of Migraine Prevention Medications
No therapeutic response with > 2 of the following 8 medication categories for prophylactic 
treatment of migraine after an adequate therapeutic trial. These medication categories are:
o
Category 1: Divalproex sodium, sodium valproate
o
Category 2: Topiramate, carbamazepine, gabapentin
o
Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, 
nebivolol, pindolol, propranolol, timolol)
o
Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, 
protriptyline)
o
Category 5: Serotonin-norepinephrine reuptake inhibitors (for example: venlafaxine, 
desvenlafaxine, duloxetine, milnacipran)
o
Category 6: Flunarizine, verapamil
o
Category 7: Lisinopril, candesartan
o
Category 8: Botox®
No therapeutic response is defined as no reduction in headache frequency, duration, or severity 
after administration of the medication for at least 6 weeks at the generally-accepted therapeutic 
dose(s) based on the investigator’s assessment.
The following scenarios do not constitute lack of therapeutic response:
o
Lack of sustained response to a medication
o
Failure to tolerate a therapeutic dose


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