Clinical trial NCT03941834
Conditions: Trigeminal Neuralgia
Keywords: Trigeminal Neuralgia, Pain
Sponsor: Pfizer
Start date: 2019-06-25; Completion date: 2023-05-11
Enrollment: 65 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to evaluate the efficacy of BHV3000 compared to placebo for subjects with treatment refractory Trigeminal Neuralgia as measured by a 2-point or greater reduction in the average Numeric Pain Rating Scale between the two-week treatment phases.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Rimegepant intervention 2: Placebo
Intervention descriptions: intervention 1: BHV3000 (rimegepant) 75mg tablet intervention 2: Placebo

Protocol documents:
Prot_000.pdf: 
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SAP_001.pdf: 
Statistical Analysis Plan v2.0 
BHV3000-202 
Confidential 
Page 1 of 41 
Confidentiality 
This document is confidential and proprietary property of Pfizer Inc. and to be used only as authorized by Pfizer 
Inc. No part is to be reproduced, disclosed to others, or quoted without prior written authorization from Pfizer Inc. 
 
 
 
 
 
 
 
Protocol BHV3000-202 
 
 
BHV3000-202: Phase 2: A Double-Blind, Placebo Controlled, Crossover Trial 
of BHV-3000 (Rimegepant) for Treatment Refractory Trigeminal Neuralgia 
 
 
Statistical Analysis Plan 
 
 
 
 
Version 2.0 
Date: 28-Aug-2023 


Statistical Analysis Plan v2.0 
BHV3000-202 
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Confidentiality 
This document is confidential and proprietary property of Pfizer Inc. and to be used only as authorized by Pfizer 
Inc. No part is to be reproduced, disclosed to others, or quoted without prior written authorization from Pfizer Inc. 
 
 
PPD 
SIGNATURE PAGE 
BHV3000-202: Phase 2: A Double-Blind, Placebo 
Controlled, Crossover Trial of BHV-3000 
(Rimegepant) for Treatment Refractory Trigeminal 
Neuralgia 
 
Document Version: 
2.0 
Date: 
28-Aug-2023 
Author: 
 
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). 
PPD 
Sponsor Signatories: 
Signature:_ 
Date: 
 
_ 
PPD 
PPD 
PPD 
      
              
PPD 
Protocol Title: 


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TABLE OF CONTENTS 
SIGNATURE PAGE .......................................................................................................... 2 
LIST OF FIGURES ........................................................................................................... 4 
REVISION HISTORY ....................................................................................................... 5 
ABBREVIATIONS ............................................................................................................ 6 
1 
Background and Rationale ......................................................................................... 8 
1.1 
Research Hypothesis .............................................................................................. 8 
1.2 
Schedule of Analyses .............................................................................................. 8 
2 
Study Description ........................................................................................................ 9 
2.1 
Study Design ........................................................................................................... 9 
2.2 
Treatment Assignment ......................................................................................... 10 
2.3 
Blinding and Unblinding ...................................................................................... 11 
2.4 
Protocol and Protocol Amendments ................................................................... 11 
3 
Study Objectives and Estimands ............................................................................. 12 
3.1 
Objectives .............................................................................................................. 12 
3.1.1 
Primary Objective .......................................................................................... 12 
3.1.2 
Secondary Objectives ..................................................................................... 12 
CCI  
3.2 
Estimands .............................................................................................................. 12 
3.2.1 
Primary Objective Estimand ......................................................................... 13 
3.2.2 
Secondary Objective Estimands .................................................................... 14 
CCI  
4 
Analysis Sets, Treatment Groups, and Subgroups ................................................. 16 
4.1 
Analysis Sets .......................................................................................................... 16 
4.2 
Treatment Groups ................................................................................................ 16 
5 
Sample, Power, and Type I Error ............................................................................ 16 
6 
Statistical Analyses .................................................................................................... 17 
6.1 
General .................................................................................................................. 17 
6.1.1 
Programmed Output ...................................................................................... 17 
6.1.2 
Statistical Methods ......................................................................................... 17 
6.1.3 
Handling of Missing Data .............................................................................. 17 
6.2 
Study Population .................................................................................................. 18 
6.2.1 
Analysis Sets .................................................................................................... 18 
6.2.2 
Enrollment ...................................................................................................... 18 
6.2.3 
Subject Disposition ......................................................................................... 18 
6.2.4 
Protocol Deviations ......................................................................................... 19 
6.2.5 
Baseline Characteristics ................................................................................. 19 
6.2.6 
Exposure .......................................................................................................... 20 
6.3 
Efficacy .................................................................................................................. 23 
6.3.1 
Continuous Efficacy Endpoints ..................................................................... 25 
6.3.2 
Continuous Efficacy Endpoints without Baseline Measurement ................ 25 
6.3.3 
Binary Efficacy Endpoints ............................................................................. 26 
6.3.4 
P01: Primary Efficacy Endpoint: NPRS ...................................................... 26 
6.3.5 
Secondary Efficacy Endpoints ....................................................................... 27 
6.4 
Safety Analyses ..................................................................................................... 28 
6.4.1 
Adverse Events ............................................................................................... 28 
6.4.2 
Laboratory Tests ............................................................................................ 31 
6.4.3 
Vital Signs and Physical Measurements ....................................................... 34 
6.4.4 
Electrocardiograms ........................................................................................ 35 
6.4.5 
Sheehan-Suicidality Tracking Scale (S-STS) ................................................ 35 


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6.4.6 
Concomitant Procedures ................................................................................ 35 
6.4.7 
Covid-19 Impact ............................................................................................. 35 
CCI 
7 
Conventions ............................................................................................................... 35 
7.1 
General .................................................................................................................. 35 
7.1.1 
Output Layout ................................................................................................ 35 
7.2 
Analysis Periods .................................................................................................... 36 
8 
Content of Reports .................................................................................................... 37 
9 
Appendices ................................................................................................................. 37 
9.1 
Relevant Protocol Deviations ............................................................................... 37 
10 References .................................................................................................................. 41 
 
LIST OF TABLES 
Table 1: 
Primary Objective Estimand .................................................................. 13 
Table 2: 
Secondary Objective Estimands ............................................................. 14 
Table 3: 
Primary and Secondary Efficacy Estimands and Analyses ................... 24 
 
LIST OF FIGURES 
Figure 1: 
Study Schematic ......................................................................................... 9 


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REVISION HISTORY 
 
Version 
Description of Change 
1.0 (Final) 
Initial version 
2.0 (Final) 
Amendment to incorporate the following changes: 
Section 3.2 Estimands: Updated Intercurrent Events section with appropriate 
strategies for safety and secondary efficacy endpoints (Penn-FPS-R, Pain 
Disability Index). 
Section 6.2.5 Baseline Characteristics: Added definition of OL baseline 
Section 6.3 Efficacy: Updates on analysis visit window definitions 
Section 6.4.1 Adverse Events: Added analysis period window definitions 
Section 7.2 Analysis Periods: Updated definitions of analysis periods 
Section 7.3 Analysis Visit Windows: Section removed; analysis visit 
windows no longer apply 
Other minor wording and typographical updates throughout the document 


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ABBREVIATIONS 
 
Abbreviation 
Definition 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
CI 
Confidence interval 
COVID-19 
Coronavirus Disease 2019 
CPK 
Creatine phosphokinase 
CRF 
Case Report Form 
CSR 
Clinical study report 
DBT 
Double-blind treatment 
ECG 
Electrocardiogram 
eDISH 
Evaluation of drug-induced serious hepatotoxicity 
eGFR 
Estimated glomerular filtration rate 
GGT 
Gamma-glutamyl transferase 
HbA1C 
Hemoglobin A1C 
HDL 
High-density lipoprotein 
IR 
Immediate release 
IWRS 
Interactive Web-based Response System 
LDL 
Low-density lipoprotein 
LFT 
Liver function test 
LSMeans 
Least square means 
MDRD 
Modification of diet in renal disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mITT 
Modified Intent to Treat 
MMRM 
Mixed-effect Model for Repeated Measures 
NPRS 
Numeric Pain Rating Scale 
OLE 
Open-label extension 
Penn-FPS-R 
Penn Facial Pain Scale-Revised 
PGI-C 
Patient Global Impression of Change Scale 
PI 
Principal Investigator 
PID 
Patient Identification Number 


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• 
 
Abbreviation 
Definition 
PT 
Prefened te1m 
QD 
Once Daily 
SAE 
Serious Adverse Event 
SAP 
Statistical analvsis plan 
SD 
Standard deviation 
SE 
Standard enor 
SI 
Svsteme Internationale 
soc 
System Organ Class 
S-STS 
Sheehan Suicidalitv Tracking Scale 
T4 
Thyroxine 
TBL 
Total bilirubin 
TEAE 
Treatment-Emergent Adverse Events 
TLF 
Tables, listings, and fomres 
TN 
Trigeminal Nemalgia 
TSH 
Thyroid stimulating honnone 
ULN 
Upper Limit ofN01mal 
us 
United States 
WHO 
World Health Organization 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1 BACKGROUND AND RATIONALE 
This document presents the statistical analysis plan (SAP) for Pfizer Inc. Protocol: BHV3000- 
202: Phase 2: A Double-Blind, Placebo Controlled, Crossover Trial of BHV-3000 (Rimegepant) 
for Treatment Refractory Trigeminal Neuralgia (TN). 
This SAP is based on the final protocol version 9.0 dated April 8, 2022. It contains the analysis 
details and methodology to address the study objectives, including planned summary tables, by- 
subject listings, and figures, which will provide the basis for the results section of the clinical 
study report (CSR). Operational aspects related to collection and timing of planned clinical 
assessments are not repeated in this SAP unless relevant to the planned analyses. 
The Rimegepant (BHV3000) Core SAP describes analysis details and methodologies common 
to the BHV3000 program and is incorporated by reference. The Core SAP assumes primacy for 
any matter where this SAP is silent (and the relevant content of the Core SAP could feasibly 
apply) or where the Core SAP is directly referenced as applicable. Otherwise, should any 
discrepancy exist between the Core SAP and this SAP, this SAP assumes primacy. 
Note that the study was terminated prematurely in 1Q2023 due to low enrollment. As a result, 
only critical data would be analyzed for the CSR. 
1.1 
Research Hypothesis 
Rimegepant is superior to placebo in providing symptom relief for treatment-refractory patients 
with classical or idiopathic trigeminal neuralgia. 
1.2 
Schedule of Analyses 
The final analysis of the Double-blind Treatment (DBT) Phase will occur after the last subject 
randomized has completed this phase of the study or discontinues from the DBT Phase. The 
study will be unblinded and analyses will summarize all efficacy, safety, laboratory and other 
data collected throughout the DBT phase of study. 
A final analysis of the study will be completed after the last subject has completed their last 
study visit of the Open-Label Extension (OLE) Phase of the study. These analyses will 
summarize all efficacy, safety, laboratory and other data collected throughout the OLE Phase of 
the study. In addition throughout the study, data may be locked, analyses conducted, and reports 
produced as required to support safety monitoring or regulatory requirements. 


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2 STUDY DESCRIPTION 
2.1 
Study Design 
BHV3000-202 is a phase 2, multi-center, double-blind, placebo controlled, crossover trial to 
assess the safety, tolerability, and efficacy of rimegepant in treating TN in patients who failed to 
respond adequately to or had intolerance or a contraindication to pharmacotherapy. Current 
inadequate response to therapy is defined by a daily pain score of greater than or equal to 4 on 
 -point Numerical Pain Rating Scale (NPRS) during the 14 days 
prior to baseline. A crossover design with a placebo washout period of 7 days between 
treatments will be used due to the limited number of subjects, with each patient serving as their 
own control. The study will be conducted at multiple centers. 
Figure 1 displays the study design. 
Figure 1: 
Study Schematic 
 
Prior to randomization, patients will enter a 14 to 30 day screening period during which they will 
complete daily self-reported assessments of pain intensity over a 24 hour period using an 11 
point NPRS, ranging from 0 (for no pain) to 10 (for the worst imaginable pain). Throughout the 


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study, patients will be allowed to remain on their current medication regimens, provided they 
have been on a stable dose for a minimum of 4 weeks prior to the randomization visit. 
Patients with a mean 
 on the 11 point NPRS, during the 
last 14 days of the screening period, will be randomized to one of two treatment sequences to 
receive rimegepant 75 mg immediate release (IR) tablet administered orally vs placebo. Each 
sequence will include a 2-week treatment phase, with daily dosing of study drug or placebo. This 
will be followed by a 7-day placebo washout period. After the placebo washout period, another 
2-week treatment phase will follow, again with once daily dosing of study drug or placebo. In 
the first sequence, patients will receive placebo for the first treatment period and rimegepant 75 
mg IR tablet during the second treatment period. The second sequence will receive rimegepant 
75 mg IR tablet during the first 2 week treatment period, followed by placebo in the second 
treatment phase. 
During each 2 week treatment phase and during the 7 day placebo washout period, patients will 
complete the 11 point NPRS daily, as described above. In addition, patients will complete a 
paper diary daily to record efficacy data. The diary will include the daily recording of overall 
pain using the 11 point NPRS, a recording of daily use of rescue medications, and a daily rating 
of worst pain episode using the 11 point NPRS. Other secondary endpoints will be assessed at 
the beginning and end of each treatment period, including the Penn Facial Pain Scale (a 12-item 
activities of daily living scale designed specifically to assess impact of TN symptoms on daily 
activities), the Pain Disability Index (which measures the degree to which chronic pain interferes 
with 7 categories of daily activities, measured on an 11 point scale ranging from 0 (no disability) 
to 10 (worst disability)). The Patient Global Impression of Change (PGI-C: a patient self- 
reported global index scale) will be assessed at the end of each treatment sequence. In addition, 
the Sheehan-Suicidality Tracking Scale (S-STS) will be administered as a safety measure at 
screening, as well as at every visit, as specified in the protocol. 
In addition, subjects completing the DBT Phase of the study and who continue to meet 
inclusion/exclusion criteria may be offered up to 12 weeks of OLE treatment, provided the 
Principal Investigator (PI) believes open-label treatment offers an acceptable risk-benefit profile. 
Subjects who agree to enter the OLE Phase will not be required to have a wash-out period of 
drug, but instead should continue dosing as specified in the OLE Phase. 
All subjects will undergo a post study Follow-up Safety Visit 14 days after the final EOT Visit 
and last dose of study drug/medication administration. Subjects who discontinue from the study 
at any time during either the DBT Phase or the OLE Phase are expected to complete the End of 
Treatment (day 119) Visit and the 2-Week Follow-up Safety Visit. 
2.2 
Treatment Assignment 
Approximately 120 patients will be screened to randomize 60 patients in a 1:1 ratio into 2 
treatment sequences receiving 75 mg rimegepant vs placebo, using a 2-period, 2-sequence, 
crossover design. Patients with atypical TN and typical TN will be stratified equally into each of 
the two treatment sequences, with atypical TN patients not exceeding 50 percent of the subjects. 
Treatment assignments will be obtained by the investigator (or designee) via the Interactive 
Web-based Response System (IWRS). 


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2.3 
Blinding and Unblinding 
This study is blinded to study drug active status (rimegepant vs placebo) through the final 
analysis of the DBT Phase (see Section 1.2). Draft TLFs are produced with dummy treatment 
groups prior to the DBT Phase database lock. TLFs for the DBT Phase and subsequent database 
locks are produced unblinded. 
2.4 
Protocol and Protocol Amendments 
BHV3000-202 SAP Version 2.0 is based on BHV3000-202 Protocol Version 9.0 (08-Apr-2022). 


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3 STUDY OBJECTIVES AND ESTIMANDS 
3.1 
Objectives 
3.1.1 
Primary Objective 
To evaluate the efficacy of rimegepant compared to placebo in providing symptomatic pain relief 
in patients with refractory TN, defined as a reduction from baseline in the average daily NPRS 
between the two-week treatment phases. 
3.1.2 
Secondary Objectives 
1. To assess the safety and tolerability of rimegepant relative to placebo in patients with TN 
2. To evaluate the efficacy of rimegepant vs placebo for improving physical function in TN 
patients as measured by the Penn Facial Pain Scale-Revised (Penn-FPS-R) 
3. To evaluate the efficacy of rimegepant vs placebo for improving functional disability in TN 
patients as measured by the Pain Disability Index 
4. To evaluate the efficacy of rimegepant vs placebo on global functioning as measured by the 
PGI-C 
5. To evaluate the efficacy of rimegepant vs placebo in providing symptomatic pain relief as 
captured by daily rating of worst pain episode as measured by the 11 point NPRS 
6. To evaluate the efficacy of rimegepant vs placebo in providing symptomatic pain relief of 
clinical importance as defined by a 2-point or greater reduction in the 11 point NPRS 
CCI  
 
 
 
3.2 
Estimands 
An estimand is the target of estimation to address the scientific question of interest posed by a 
study objective. The 4 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 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 protocol for 
inclusion/exclusion criteria. 
Intercurrent Events 
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: 


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Study drug discontinuation before the time point of interest defining the endpoint. 
o For safety objectives: 
-on-treatment 
the 
intercurrent event of interest, such that all observed values of the endpoint 
of interest will be used prior to study drug discontinuation. 
 
For all other safety endpoints, study drug discontinuation is handled with a 
 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. 
o For efficacy objectives: 
 
For the NPRS objectives, study drug discontinuation is handled with a 
while-on-treatment strategy . 
 
For the Penn-FPS-R, PDI, and PGI-C efficacy objectives, study drug 
discontinuation is handled with a treatment policy strategy . 
o For all other objectives (i.e., use of non-study TN standard of care medications on 
or before the time point of interest), this intercurrent event will be handled with a 
while-on-treatment strategy  
3.2.1 
Primary Objective Estimand 
Table 1 presents the estimand for the primary objective. 
Table 1: 
Primary Objective Estimand 
 
Objective 
To evaluate the efficacy of rimegepant compared to placebo in providing 
symptomatic pain relief in patients with refractory TN, defined as a reduction from 
baseline in the average daily NPRS between the two-week treatment phases. 
Efficacy Endpoint  Change from baseline to the average of the 2-week treatment phase of the study in the 
average daily NPRS 
Summary 
Using the modified Intent to Treat (mITT) population: 
 
Descriptive statistics for the averaged daily NPRS score and change from baseline 
score as a continuous variable by treatment group at each 2-week treatment phase 
 
Difference in mean change from baseline in average daily NPRS scores between 
treatment groups estimated using a mixed-effect model for repeated measures 
(MMRM) 
Intercurrent 
Events 
Study drug discontinuation: while-on-treatment strategy 
 
 


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3.2.2 
Secondary Objective Estimands 
Table 2 presents the estimands for secondary objectives. 
Table 2: 
Secondary Objective Estimands 
 
Objective 1 
To assess the safety and tolerability of rimegepant relative to placebo in 
patients with TN 
Safety Endpoint 
Frequency of unique subjects with: SAEs, AEs leading to discontinuation, AEs 
judged to be related to study medication, S-STS total score, and clinically significant 
electrocardiogram (ECG) and laboratory abnormalities observed during the 
randomization phase of the study 
Summary 
Using the treated subjects population: 
 
Number and percentage of subjects with these events or findings 
Intercurrent Events  Study drug discontinuation: while-on-treatment strategy for AEs; treatment policy 
strategy for all other safety endpoints 
 
Objective 2 
To evaluate the efficacy of rimegepant vs placebo for improving physical 
function in TN patients as measured by Penn-FPS-R 
Efficacy Endpoint 
Change in Penn-FPS-R total score from baseline to the end of the 2-week treatment 
phase of the study 
Summary 
Using the mITT population: 
 
Descriptive statistics for Penn-FPS-R and change from baseline as a 
continuous variable by treatment group at each visit 
 
Difference in mean change from baseline in Penn-FPS-R scores between 
treatment groups estimated using MMRM 
Intercurrent Events 
Study drug discontinuation: treatment policy strategy 
 
Objective 3 
To evaluate the efficacy of rimegepant vs placebo for improving functional 
disability in TN patients as measured by the Pain Disability Index 
Efficacy Endpoint 
Change in Pain Disability Index total score from baseline to the end of the 2-week 
treatment phase of the study 
Summary 
Using the mITT population: 
 
Descriptive statistics for Pain Disability Index and change from baseline as a 
continuous variable by treatment group at each visit 
 
Difference in mean change from baseline in Pain Disability Index between 
treatment groups estimated using MMRM 
Intercurrent Events 
Study drug discontinuation: treatment policy strategy 
 
Objective 4 
To evaluate the efficacy of rimegepant vs placebo on global functioning as 
measured by the PGI-C 
Outcomes Research 
Endpoint 
PGI-C Scale at the end of the 2-week treatment phase of the study 
Summary 
Using the mITT population: 
 
Descriptive statistics for PGI-C score as categorical variable by treatment group 
at each visit 
 
Difference in PGI-C score between treatment groups estimated using MMRM 
 


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Intercurrent Events 
Study drug discontinuation: treatment policy strategy 
 
Objective 5 
To evaluate the efficacy of rimegepant vs placebo in providing symptomatic 
pain relief as captured by daily rating of worst pain episode as measured by the 
11 point NPRS 
Effiacy Endpoint 
Change from baseline to the average worst pain NPRS scores in a day in the 2-week 
treatment phase of the study 
Summary 
Using the mITT population: 
 
Descriptive statistics for the average worst pain episode NPRS scores and 
change from baseline score as a continuous variable by treatment group for 
each 2-week treatment phase 
 
Difference in mean change from baseline in the average worst pain episode 
NPRS scores between treatment groups estimated using MMRM 
Intercurrent Events 
Study drug discontinuation: while-on-treatment strategy 
 
Objective 6 
To evaluate the efficacy of rimegepant vs placebo in providing symptomatic 
pain relief of clinical importance as defined by a 2-point or greater reduction 
in the 11 point NPRS 
Effiacy Endpoint 
Percentages 
 point reduction from baseline in average daily 
NPRS score 
Summary 
Using the mITT population: 
 
Number and percentages by treatment group and odds ratio between treatment 
groups using logistic regression 
Intercurrent Events 
Study drug discontinuation: while-on-treatment strategy 
 
CCI  
 


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4 ANALYSIS SETS, TREATMENT GROUPS, AND SUBGROUPS 
4.1 
Analysis Sets 
The following analysis sets will be evaluated and used for presentation and analysis of the data: 
 
Enrolled: Patients who signed an informed consent form and were assigned a Patient 
Identification number (PID). 
 
Full: Enrolled subjects who received a treatment assignment from the IWRS (rimegepant 
or placebo). 
 
Treated: Enrolled subjects who received at least 1 dose of study therapy (rimegepant or 
placebo). 
o DBT treated: Subjects in the treated analysis set who took  1 dose of DB study 
drug (rimegepant or placebo), i.e., nonmissing study drug start date. 
o Interim treated: Subjects in the treated analysis set with safety data entered during 
the interim period (post-DBT pre-OL period). 
o OL rimegepant treated: Subjects in the treated analysis set who took  1 dose of 
OL rimegepant, i.e., nonmissing OL rimegepant start date. 
o DB or OL rimegepant treated: Subjects in the treated analysis set who took  1 
dose of DB or OL rimegepant, i.e., nonmissing DB or OL rimegepant start date. 
o Follow-up treated: subjects in the treated analysis set whose last contact date is in 
the follow-up period. 
 
Modified Intent to Treat (mITT): Randomized subjects who received at least 1 dose of 
study therapy and provided a baseline and at least one post-baseline efficacy assessment 
in each sequence. 
4.2 
Treatment Groups 
Treatment groups in the DBT phase are rimegepant 75 mg and placebo. The treatment group in 
the OLE phase is rimegepant 75 mg. 
Populations of treated subjects will be assessed by the as-treated treatment group; i.e., by the 
treatment actually received. Otherwise, all other populations and all efficacy analyses will be 
assessed by the as-randomized treatment group. The enrolled population will be assessed overall. 
5 SAMPLE, POWER, AND TYPE I ERROR 
The sample size for this study will be approximately 60 randomized patients. Approximately 120 
patients will be screened, assuming no more than 50 percent of patients would be ineligible for 
randomization. 
The calculation for the sample size was based on a paired t-test crossover design, assuming a low 
correlation (r = 0.2) between the active and placebo response to treatment. Assuming a paired 
difference standard deviation of 3.8, 60 randomized patients will provide >90% power to detect a 
2-point difference between rimegepant and placebo using a two-sided significance level of 0.05 
and a 20% dropout rate with no imputation. 


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Type 1 error is not applicable. The significance of the primary and secondary endpoints will not 
be evaluated. 
6 STATISTICAL ANALYSES 
6.1 
General 
6.1.1 
Programmed Output 
A list of TLFs and corresponding templates are presented separately in a mock TLF document 
corresponding to this SAP. 
Refer to the Core SAP for additional details about programmed output. 
Medical history and AEs are coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) most recent version available. 
Concomitant medications are coded using the World Health Organization Drug Global 
Dictionary (WHODrug Global), most recent version available. 
All statistical analyses will be performed using SAS statistical software (Version 9.4 or higher), 
unless otherwise noted. 
6.1.1.1 
Tables 
Tables will be summarized by treatment sequence and period, rimegepant pooled, placebo 
pooled, and overall. Exceptions are specified in subsequent sections as needed. 
6.1.1.2 
By-Subject Listings 
By-subject listings will present all data by randomization status (randomized, not randomized), 
site-subject ID, and additional variables such as time points, as applicable. Listings display as- 
randomized treatment sequence 
- 
Sequence 1 subjects 
- 
 
 Sequence 2 subjects 
Refer to the Core SAP for additional details about listings. 
6.1.2 
Statistical Methods 
Refer to the Core SAP for descriptive statistics in summary tables, counting rules in frequency 
tables, and rounding rules. 
Categorical variables will be tabulated with the count and percentage within each category (with 
a 
 category if applicable). Continuous variables will be summarized with univariate 
statistics (e.g., n, mean, median, standard deviation (SD), minimum, and maximum). 
Tabulations of the following endpoints present the number of unique subjects with an event: 
protocol deviations; non-study medications; AEs; and laboratory abnormalities. Thus, for these 
endpoints, multiple occurrences of the same event are counted only once per subject. 
6.1.3 
Handling of Missing Data 
Unless otherwise noted, efficacy analyses will be based on observed data only. For the main 
analyses of efficacy for primary and secondary endpoints, no imputation will be performed to 
impute data following discontinuation from study. 


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For efficacy analyses, partial or missing dates will not be imputed. The relative study days, 
where determined, will be calculated for full dates only. 
6.2 
Study Population 
6.2.1 
Analysis Sets 
The number of subjects in each analysis set described in Section 4.1 is tabulated by treatment 
sequence (as-randomized for the full and mITT analysis sets; as-treated for the treated analysis 
set), not randomized, and overall. 
A by-subject listing of analysis sets is provided for the enrolled analysis set, which includes the 
reason for exclusion (i.e., not treated with study drug). Treated subjects may have > 1 exclusion 
reason. 
A by-subject administrative listing of randomization scheme and codes is provided for all 
randomization numbers and block numbers, even those not assigned to a subject. 
6.2.2 
Enrollment 
Enrollment by country and site is tabulated overall for the enrolled analysis set, full analysis set, 
and safety analysis set. 
6.2.3 
Subject Disposition 
Results are based on the Study Termination Summary case report form (CRF). A by-subject 
listing of subject disposition by study phase will be produced for the enrolled analysis set. Refer 
to Section 6.2.3.1 of the Core SAP for more details. 
6.2.3.1 
Subject Disposition during the DBT Phase 
Subject disposition during the DBT phase will be summarized for treated subjects by as-treated 
treatment sequence and overall as the number and percentage of subjects in the following 
categories: 
 
Completed the first treatment period 
 
Withdrew from the first treatment period 
o Reasons for withdrawal, including not reported 
Completed the second treatment period 
Withdrew from the second treatment period 
o Reasons for withdrawal, including not reported. 
Continuing to the OLE phase 
Not continuing to the OLE phase 
6.2.3.2 
Subject Disposition during the OLE Phase 
Subject disposition in the OLE phase will be summarized for OLE treated subjects overall as the 
number and percentage of subjects in the following categories: 


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Completed the OLE Phase 
 
Withdrew from the OLE Phase 
o Reasons for withdrawal, including not reported. 
6.2.3.3 
Subject Disposition during the Follow-Up Phase 
Subject disposition in the follow-up phase will be summarized for treated subjects overall as the 
number and percentage of subjects in the following categories: 
 
Completed the follow-up safety visit 
 
Did not complete the follow-up safety visit 
o Reasons for not completing 
6.2.4 
Protocol Deviations 
6.2.4.1 
Relevant Protocol Deviations 
The frequency table of relevant protocol deviations are provided as the number and percentage of 
subjects in deviation categories by treatment sequence and overall for the full analysis set. 
Results are shown by deviation type (eligibility, subject management), category, and subcategory 
in the order specified in Section 9.1. Results for all relevant protocol deviation categories and 
subcategories are displayed, even those with 0 counts, unless specified otherwise. See Section 
6.2.4.1 of the Core SAP for further details. 
A by-subject listing of relevant protocol deviations is provided for the full analysis set. This 
includes deviation type, category, and subcategory, which are additional sorting variables. 
6.2.4.2 
Significant Protocol Deviations 
Significant protocol deviations are non-programmable deviations that do not impact the 
interpretability of study data. A subject listing of significant protocol deviations is a manually 
generated appendix provided by clinical operations for inclusion in the CSR. 
A by-subject listing of significant protocol deviations is provided for the enrolled analysis set. 
This includes visit, deviation type, deviation description, and specify, which are used as 
additional sorting variables. 
6.2.5 
Baseline Characteristics 
Baseline characteristics include: (1) demographics and other relevant baseline characteristics, (2) 
neurological exam results, (3) medical history, and (4) non-study prior medications. Tables will 
be summarized by treatment sequence and overall, unless otherwise specified. 
Tables of baseline characteristics are provided for the DBT treated analysis set. 
The frequency table of randomization stratum (i.e., atypical and typical TN) is provided for the 
full analysis set by as-randomized treatment sequence and overall. 
For the DB treated and Follow-up treated analysis set, baseline is defined as the last non-missing 
value at or before the study drug start date/time (rimegepant or placebo) during period 1 of the 2- 
period sequence. For other analysis sets, refer to the Core SAP for details on baseline for a 
parameter (e.g., weight), including handling of ties on the same measurement date. For the OL 


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rimegepant treated analysis set, baseline is defined as the last non-missing value at or before the 
OL study drug start date/time. 
By-subject listings are provided for the enrolled analysis set for (1) through (4) above. 
6.2.5.1 
Demographics and Other Relevant Baseline Characteristics 
Refer to the Core SAP for the table of demographics and other relevant baseline characteristics, 
and calculating age at a reference date. Other relevant characteristics also include the following: 
neuralgia type (typical, atypical), MRI confirmed Classical TN diagnosis (yes, no). 
6.2.5.2 
Medical History 
The frequency table of medical history is provided by system organ class (SOC) and preferred 
term (PT), and displayed in descending order of overall frequency within SOC and PT. Refer to 
the Core SAP (Section 6.2.5.3) for medical history. 
6.2.5.3 
Non-study Prior Medications 
Frequency tables of non-study prior medications (i.e., previous or current medications) is 
provided by therapeutic class and preferred name in descending order of overall frequency 
within therapeutic class and preferred name. The definitions of medication types in Section 
6.2.6.3 of the Core SAP applies. 
6.2.6 
Exposure 
Analyses are based on as-treated treatment group to support safety, unless specified otherwise. 
6.2.6.1 
Study Therapy 
During the DBT Phase of the study, subjects will be randomized to a sequence of either 
rimegepant (75 mg QD) and then placebo or placebo then rimegepant (75 mg QD) in a 2- 
sequence, 2-period, crossover design. Study drug/medication will be dispensed at the baseline 
visit and at Days 14 and 21. Subjects should take the first dose the day of the baseline visit. 
Study drug/medication should be administered in the morning without regard to meals. Subjects 
who showed continued compliance during the DBT Phase may choose to enter a 12 week OLE 
Phase with daily dosing of rimegepant (75 mg QD) ODT. Open label study drug will be 
dispensed at the Day 35 visit for subjects who enter the OLE Phase. Subjects should take the first 
dose of OLE study drug on Day 36. 
Subjects report study drug exposure in the subject paper study log (diary), whereas sites report 
study drug accountability on the Study Drug Dispensing Log CRF. 
An administrative listing of IP batch numbers is provided for the treated analysis set. Refer to the 
Core SAP for listing contents. 
DB Study Drug (Rimegepant or Placebo) Exposure 


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DB rimegepant or placebo exposure will be summarized descriptively by as-treated treatment 
groups for period 1 placebo, period 1 rimegepant, period 2 rimegepant, period 2 placebo, 
rimegepant pooled, placebo pooled and overall, and will include the following parameters: 
 
Time on DBT (days), derived as DBT end date  DBT start date + 1 
 
Time on DBT study drug category (weeks) 
 
Cumulative DBT exposure (mg), derived by summing number of DB mg across DB 
study drug records 
 
Average DBT exposure (mg per day), derived as cumulative DB exposure/time on DBT 
 
Total DBT exposure (tablets) summed across all subjects, derived by summing 
cumulative DB exposure across all subjects. 
 
Total DBT exposure (patient-years), derived by summing (DBT end date  DBT start 
date + 1)/365.25 across all subjects. 
OL Rimegepant Exposure 
OL rimegepant exposure will be summarized descriptively by treatment sequence and overall, 
and will include the following parameters: 
 
Time on OL rimegepant (days), derived as OL rimegepant end date  OL rimegepant 
start date + 1 
 
Time on OL rimegepant category (weeks) 
 
Cumulative OL rimegepant exposure (mg), derived by summing number of OL mg 
across records with non-missing OL rimegepant date/times. 
 
Average OL rimegepant exposure (mg per day), derived as cumulative OL rimegepant 
exposure/time on OL rimegepant 
 
Total OL rimegepant exposure (tablets) summed across all subjects, derived by summing 
cumulative OL rimegepant exposure 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. 
DB or OL Rimegepant Exposure 
DB or OL rimegepant exposure will be summarized descriptively by as-treated DB rimegepant 
pooled/OL rimegepant, DB placebo pooled/OL rimegepant and overall, and will include the 
following parameters: 
Time on DB or OL rimegepant (days), derived as DB or OL rimegepant end date DB or 
OL rimegepant start date + 1 
Time on DB or OL study drug category (weeks) 
Cumulative DB or OL rimegepant exposure (mg), derived by summing number of DB or 
OL mg across records with non-missing DB or OL rimegepant date/times. 
Average DB or OL rimegepant exposure (mg per day), derived as cumulative DB or OL 
rimegepant exposure/time on DB or OL rimegepant. 


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Total DB or OL rimegepant exposure (tablets) summed across all subjects, derived by 
summing cumulative DB or OL rimegepant exposure across all subjects. Total DB or OL 
rimegepant exposure includes missed dose days within a study phase and excludes the 
dosing break between study phases (i.e., (last dose day of DB study drug  first dose date 
of DB study drug + 1)  (number of days with a dosing break between the DB and OL 
phases)). 
 
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. 
 
A by-subject listing of study drug exposure will be provided for the treated analysis set. 
6.2.6.2 
Drug Accountability and Compliance 
DB study drug accountability and compliance will be tabulated by as-treated treatment groups 
for period 1 placebo, period 1 rimegepant, period 2 rimegepant, period 2 placebo, rimegepant 
pooled, placebo pooled, and overall with the number and percentage of subjects in the following 
categories for the DB phase: 
 
Any bottle dispensed (Yes, No, Not Reported) 
 
DB study drug taken but not randomized 
 
Tablet count compliance < 80% from study drug start to study drug end in DB phase 
 
More than the required number of tablets administered on 1 day 
 
Did not return  1 bottle dispensed and discontinued study drug, defined as any of the 
following: 
o Randomized subjects who were not treated and did not return DB bottle dispensed 
o Treated subjects who did not return  1 DB bottle dispensed and discontinued 
DBT (i.e., non-missing DBT last date) 
 
Did not return any bottle dispensed and discontinued study drug 
 
No study drug taken for  3 days (not necessarily consecutive) in any 1 week 
 
Incorrect study drug taken (all the time; at least once) 
OL study drug accountability and compliance will be tabulated overall for the OLE phase: 
 
Tablet count compliance < 80% from study drug start to study drug end in OLE phase 
 
More than the required number of tablets administered on 1 day 
 
Did not return  1 bottle dispensed and discontinued study drug, defined as: OL 
rimegepant treated subjects who did not return  1 OL rimegepant bottle dispensed and 
discontinued OL rimegepant (i.e., non-missing OL rimegepant last date). 
 
Did not return any bottle dispensed and discontinued study drug 
 
No study drug taken for  3 days (not necessarily consecutive) in any 1 week 
 
A by-subject listing of treatment compliance will be provided for the treated analysis set. 


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6.2.6.3 
Non-study Medications 
Non-study medications will be identified from the Concomitant Medications and Rescue Pain 
Medications CRFs. Recue medications are defined as non-study medications reported on the 
Rescue Pain Medication CRF. Rescue medication dates and times are not imputed. 
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. 
A by-subject listing of concomitant medications, inclusive of rescue medications, is provided by 
therapeutic class and preferred name for the enrolled subjects. Medication types are identified. 
Refer to the Core SAP for listing contents. 
Refer to the Core SAP for non-study medication start and stop date imputation, listing content, 
and definition of concomitant medication. 
DBT Period Non-study Medications 
Frequency tables of the following DBT period non-study medications are provided by period 1 
placebo, period 1 rimegepant, period 2 rimegepant, period 2 placebo, rimegepant pooled, and 
placebo pooled for the DBT treated subjects: concomitant medications, rescue medications. 
Medications are displayed in descending order of rimegepant pooled frequency within 
therapeutic class and preferred name. 
OL Rimegepant Period Non-study Medications 
OL rimegepant period non-study medications will be summarized analogously by treatment 
sequence and overall for the OL rimegepant treated subjects and the following medications: 
concomitant medications, rescue medications. 
6.3 
Efficacy 
Unless otherwise noted, the primary and secondary efficacy analyses will be conducted on the 
mITT population. DBT and OLE efficacy data will be included in listings by subject, treatment 
sequence and period, study phase and visit (as applicable). Descriptive summary statistics will be 
provided for DBT and OLE phase data. Statistical analyses outlined in Table 3: 
Primary and 
Secondary Efficacy Estimands and Analyses will only be done for the DBT phase data. 


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Table 3: 
Primary and Secondary Efficacy Estimands and Analyses 
 
Index 
Description 
Variable Type 
Statistical 
Model 
On-Study Data 
Primary Estimand 
P01 
Difference between treatment 
groups in change from 
baseline in average daily 
NPRS scores at the end of the 
randomization phase 
Continuous 
MMRM 
Baseline, Day 14, 
21, 35 
Secondary Estimand 
S01 
Difference between treatment 
groups in change from 
baseline in Penn-FPS-R score 
at the end of the randomization 
phase 
Continuous 
MMRM 
Baseline, Day 14, 
21, 35 
S02 
Difference between treatment 
groups in change from 
baseline in Pain Disability 
Index at the end of the 
randomization phase 
Continuous 
MMRM 
Baseline, Day 14, 
21, 35 
S03 
Difference between treatment 
groups in PGI-C at the end of 
the randomization phase 
Continuous 
MMRM 
Day 14, 21, 35 
S04 
Difference between treatment 
groups in change from 
baseline in worst pain episode 
measured by NPRS at the end 
of the randomization phase 
Continuous 
MMRM 
Baseline, Day 14, 
21, 35 
S05 
Difference between treatment 
groups in percentages of 
 point 
reduction from baseline in 
average daily NPRS score 
Binary 
Logistic 
Regression 
Baseline, Day 14, 
21, 35 
MMRM = Mixed effects model for repeated measures 


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6.3.1 
Continuous Efficacy Endpoints 
Assessments are taken directly from reported CRF visits, aside from the NPRS endpoints which 
are only taken between treatment exposure start and end dates. 
Descriptive Analyses 
Summary statistics for parameter values are tabulated at select time points by treatment group 
(rimegepant pooled or placebo pooled). 
MMRM 
Treatment groups are assessed using MMRM with the following variables: 
 
Dependent variable: change from baseline of NPRS score averaged over each DBT period 
 
Fixed effects (categorical variables): treatment group, sequence, and period 
 
Covariate (continuous variable): baseline value of dependent variable 
Random effect: subject error degrees of freedom are determined by the Kenward-Roger method. 
The following statistics are tabulated from the MMRM: 
 
Least-squares mean (LSMean) with corresponding SE with 95% confidence intervals (CIs) 
of changes from baseline by treatment group (pooled rimegepant, pooled placebo). 
 
Difference in LSMeans between treatment groups (pooled rimegepant, pooled placebo) with 
corresponding SE, and 95% CI. 
 
6.3.2 
Continuous Efficacy Endpoints without Baseline Measurement 
Assessments are taken directly from reported CRF visits. 
Descriptive Analyses 
Descriptive statistics will be presented at select time points by treatment group (rimegepant 
pooled or placebo pooled). 
MMRM 
Treatment groups are assessed using MMRM with the following variables: 
Dependent variable, e.g., PGI-C score at Day 14 (note that Day is relative to the start of each 
treatment period) 
Fixed effects (categorical variables): treatment group, sequence, and period 
Random effect: subject error degrees of freedom are determined by the Kenward-Roger 
method. 


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The following statistics are tabulated from the MMRM: 
 
LSMean with corresponding standard error (SE) with 95% CIs of values by treatment group 
 
Difference in LSMeans between treatment groups (rimegepant, placebo) with corresponding 
SE, and 95% CI. 
 
6.3.3 
Binary Efficacy Endpoints 
Assessments are taken directly from reported CRF visits, aside from the NPRS endpoints which 
are only taken between treatment exposure start and end dates. 
Descriptive Analyses 
Descriptive statistics will be presented at select time points by treatment group (rimegepant 
pooled or placebo pooled). 
Logistic Regression 
Treatment groups are assessed using Logistic Regression with the following variables: 
 
Dependent variable, e.g., 
-point reduction in average daily NPRS score 
 
Fixed effects (categorical variables): treatment group, sequence, and period 
 
Covariate (continuous variable): baseline value of NPRS 
The following statistics are tabulated from the logistic regression: 
 
-point reduction in average NPRS score by 
treatment group 
 
Observed percentage difference (rimegepant vs. placebo) 
 
Odds ratio between rimegepant and placebo with corresponding 95% CI. 
6.3.4 
P01: Primary Efficacy Endpoint: NPRS 
6.3.4.1 
Main Analyses 
The NPRS is a segmented, 11-item, numeric scale ranging from 0-10. The NPRS is anchored by 
Subjects were given a paper diary to record daily pain intensity on the NPRS. They were asked 
to keep a daily record of their average pain intensity over a 24 hour period. 
The primary endpoint is the change in average daily NPRS from baseline to the end of the 2- 
week treatment phase of the study. Pain relief is defined as an improvement (reduction) from 
baseline. The primary endpoint will estimate the effect of rimegepant relative to placebo over 2 
weeks of treatment when added to a standard of care therapy, and regardless of the effect of other 
concomitant medication. The pain score will be the average of the daily 11-point NPRS 
recorded within each period using the mITT population. This treatment effect will be 


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The Pain Disability Index is designe 
scored on an 11- 
summarized as the difference in the average daily score in total NPRS between rimegepant and 
placebo. 
The primary endpoint will be analyzed using the method specified in Section 6.3.1. The MMRM 
table has the same format as the one described in Section 6.3.1. 
6.3.5 
Secondary Efficacy Endpoints 
6.3.5.1 
S01: Penn Facial Pain Scale-Revised (Penn-FPS-R) 
The Penn-FPS-R is a 12-item scale used to assess the impact of TN pain on health-related quality 
of life and activities of daily living. Developers of the original Penn-FPS-R applied standard 
validation metrics (e.g., concept elicitation, cognitive debrief, reliability, responsiveness) to the 
Penn-FPS-R as a measure for use in assessing treatment impacts on TN symptoms. The response 
added by the Sponsor. 
Subjects are asked to complete the Penn-FPS-R at the beginning and end of each treatment 
phase, as outlined in the Schedule of Assessments. 
Change from baseline in Penn-FPS-R total score will be analyzed using the same methodology 
as the primary endpoint (see Section 6.3.4.1) with baseline total score as the covariate. 
6.3.5.2 
S02: Pain Disability Index 
 
Subjects are asked to complete the Pain Disability Index at the beginning and end of each 
treatment phase, as outlined in the Schedule of Assessments. 
Change from baseline in Pain Disability Index total score will be analyzed using the same 
methodology as the primary endpoint (see Section 6.3.4.1) with baseline index as the covariate. 
6.3.5.3 
S03: Patient Global Impression of Change Scale (PGI-C) 
The PGI-C is a patient-
 
improved or worsened relative to the baseline visit. The subject is asked to rate a change in their 
overall disease condition on a 7-
 
PGI-C is a global index scale that may be used to rate the response of a condition to a therapy. 
The PGI-C will be conducted at the beginning and end of each treatment phase as indicated in 
the Schedule of Assessments. 
The PGI-C will be analyzed using the method specified in Section 6.3.2. The MMRM table has 
the same format as the one described in Section 6.3.2. 


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of fatal; 
- 
S 
6.3.5.4 
S04: Worst Pain Episode 
Using the 11-point NPRS described above, subjects are asked to record an intensity rating of 
their worst pain episode over a 24-hour period daily in their paper diary. 
Worst pain episode score will be analyzed using the same methodology as the primary endpoint 
(see Section 6.3.4.1) with baseline score as covariate. 
6.3.5.5 
S05:  2-Point Reduction in the 11 Point NPRS 
-point reduction in average NPRS score will be analyzed using logistic 
regression, that will include terms for treatment group, randomization strata (typical/atypical), 
sequence, and baseline NPRS score. See Section 6.3.3 for details. The regression table has the 
same format as the one described in Section 6.3.3. 
6.4 Safety Analyses 
Safety outcome measures include: AEs, laboratory assessments, vital signs, ECGs, concomitant 
medications, and the S-STS questionnaire. 
Tables of safety endpoints are provided according to safety analysis period and analysis set as 
follows, unless otherwise noted: 
 
On-DBT for the DBT treated analysis set by treatment sequence and period, rimegepant 
pooled, and placebo pooled 
 
Post-DBT pre-OL rimegepant for the interim treated analysis set by treatment sequence 
and period, rimegepant pooled, placebo pooled, and overall 
 
On-OL rimegepant for the OL rimegepant treated analysis set by DB rimegepant 
pooled/OL rimegepant, DB placebo pooled/OL rimegepant, and overall. Shifts from 
baseline are based on the OL rimegepant baseline. 
 
On-DB or OL rimegepant for the DB or OL rimegepant treated analysis set by DB 
rimegepant pooled/OL rimegepant, DB placebo pooled/OL rimegepant, and overall. 
Shifts from baseline are based on the DB or OL rimegepant baseline. 
 
Follow-up for the follow-up treated analysis set by DB rimegepant pooled/OL 
rimegepant, DB placebo pooled/OL rimegepant, and overall. 
6.4.1 
Adverse Events 
Refer to the Core SAP for the following: AE start and end date imputation; death date derivation; 
rules for counting and rounding in frequency tables; definitions of treatment-emergent adverse 
events (TEAEs), AEs related to study drug, and exposure-adjusted multiple occurences of unique 
AEs; and TLF contents. 
A by-subject AE listing is provided for the enrolled analysis set. TEAEs are identified. 
6.4.1.1 
Deaths 
Deaths are identified from any of the following sources: 
 


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complete death date 
 
Study Termination Summary CRF with any of the following: death as reason for 
discontinuation; complete or partially complete death date 
The by-subject listing of deaths is provided for the enrolled analysis set. 
6.4.1.2 
AE Overviews 
An AE overview frequency table displays the following categories without SOC and PT: any 
AE; mild AE; moderate AE; severe AE; moderate or severe AE; AE related to study drug; AE 
leading to study drug discontinuation; SAE; SAE leading to study drug discontinuation; hepatic- 
related AE; cardiovascular AE; and suicidality AE. 
AE overview tables are produced for the following safety analysis periods and analysis sets: 
 
Pretreatment for the DBT treated analysis set 
 
On-DBT for the DBT treated analysis set 
 
Post-DBT pre-OL rimegepant for the interim treated analysis set 
 
On-OL rimegepant for the OL rimegepant treated analysis set 
 
On-DB or OL rimegepant for the DB or OL rimegepant treated analysis set 
 
Follow-up for the follow-up treated analysis set. 
6.4.1.3 
On-DBT AEs 
Frequency tables of on-DBT AEs are provided for the DBT treated analysis set by SOC and PT 
for the following endpoints: 
 
AEs by intensity 
 
AEs related to study drug by intensity 
 
AEs by relationship to study drug (related, possibly related, unlikely related, not related, 
not reported) 
 
SAEs 
 
AEs leading to study drug discontinuation 
 
Exposure-adjusted multiple occurrences of unique AEs 
 
Hepatic-related AEs by intensity * 
 
Cardiovascular AEs * 
 
Suicidality AEs *. 
 
AEs with a start date on or after the first dose date/time on the Day 1 visit and prior to the first 
dose date/time on the Day 21 visit is considered to be in the on-DBT analysis period 1. AEs with 
a start date on or after the first dose date/time on the Day 21 visit to the earlier of the last dose of 
the DBT + 7 or the first dose of OLE - 1 is considered to be in the on-DBT analysis period 2. 


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Calculations for on-DB rimegepant exposure-adjusted multiple occurrences of unique AEs use 
an analysis period reference start date = DB rimegepant start date, analysis period reference end 
date = DB rimegepant last date + 7 days. 
6.4.1.4 
On-OL Rimegepant AEs 
Frequency tables of on-OL rimegepant AEs are provided for the OL rimegepant treated analysis 
set by SOC and PT for the following endpoints: 
 
AEs by intensity 
 
AEs related to study drug by intensity 
 
AEs by relationship to study drug (related, possibly related, unlikely related, not related, 
not reported) 
 
SAEs 
 
AEs leading to study drug discontinuation 
AEs with a start date on or after the first dose date/time of OL rimegepant and prior to the last 
dose date of the OL rimegepant + 7 is considered to be in the on-OL analysis period. 
6.4.1.5 
On-DB or OL Rimegepant AEs 
On-DB or OL rimegepant AEs are provided for the DB or OL rimegepant treated analysis set by 
SOC and PT for the same endpoints listed in Section 6.4.1.3. 
AEs with a start date on or after the first dose date/time of DB rimegepant or OL rimegepant and 
prior to the last dose date of the DB or OL rimegepant + 7 is considered to be in the on-DB or 
OL rimegepant analysis period. 
Calculations for on-DB or on-OL rimegepant exposure-adjusted multiple occurrences of unique 
AEs use an analysis period reference start date = DB or OL rimegepant start date, analysis period 
reference end date = DB or OL rimegepant last date + 7 days. 
6.4.1.6 
Post-DBT Pre-OL Rimegepant AEs 
Frequency tables of post-DBT pre-OL rimegepant AEs are provided for the interim treated 
analysis set by SOC and PT for the following endpoints: 
 
AEs by intensity 
SAEs 
AEs leading to study drug discontinuation. 
AEs with a start date after the last dose date/time of DB + 7 and before the OL rimegepant start 
date is considered to be in the post-DB Pre-OL rimegepant analysis period. 
6.4.1.7 
Follow-up AEs 
Frequency tables of follow-up AEs are provided by SOC and PT for the follow-up treated 
analysis set for the following endpoints: 
AEs by intensity 


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SAEs. 
For subjects who did not continue into the OL rimegepant period, AEs with a start date after the 
last dose date/time of DB + 7 is considered to be in the follow-up analysis period. For subjects 
who continued into the OL rimegepant period, AEs with a start date after the last dose date/time 
of OL rimegepant + 7 days is considered to be in the follow-up analysis period. 
6.4.1.8 
AEs across All Study Phases Combined 
Frequency tables of AEs are provided by SOC and PT for the treated analysis set across all 
safety analysis periods combined for the following endpoints: 
 
AEs leading to study drug discontinuation 
6.4.2 
Laboratory Tests 
Laboratory tests of clinical interest are collected at the following visits: 
 
Hematology: Screening, Baseline (Day 1), Day 35, Day 119, Follow-up safety visit (14 
days post last dose) and early termination 
 
Serum chemistry: Screening, Baseline (Day 1), Day 35, Day 119, Follow-up safety visit 
(14 days post last dose) and early termination. Exceptions are for the following: 
o Liver function Tests (LFTs) (ALT, AST, ALP, TBL, direct bilirubin, indirect 
bilirubin): All visits except Day 21 
o Lipids (total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density 
lipoprotein [LDL] cholesterol, triglycerides), folate, HbA1C, P-Amylase or 
Lipase, TSH, and T4: Screening 
 
Urinalysis: Screening, Baseline (Day 1), Day 35, Day 119, Follow-up safety visit (14 
days post last dose) and early termination. 
Laboratory tests of clinical interest for analyses include the following: 
 
Hematology: hemoglobin, hematocrit, platelets, CBC with differential and absolute 
neutrophil count 
 
Serum chemistry: sodium, potassium, chloride, calcium, ALT, AST, LDH, alkaline 
phosphatase, GGT, phosphorous, bicarbonate, CPK, total protein, albumin, total 
bilirubin, glucose, creatinine, BUN, uric acid, total cholesterol, LDL, HDL, triglycerides, 
folate, HbA1C, P-Amylase or Lipase, TSH, and T4 
Urinalysis: macroscopic examination, pH, specific gravity, ketones, nitrites, 
urobilinogen, leukocyte esterase, protein, glucose, and occult blood. 
LFTs: ALT, AST, TBL and ALP 
Refer to the Core SAP for toxicity grading. 
Estimated glomerular filtration rate (eGFR) will be derived using the modification of diet in 
renal disease (MDRD) formula; refer to the Core SAP for additional details. 
TLFs will be provided to show data in Systeme Internationale (SI) unit system. 


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A by-subject listing of the following select laboratory tests will be provided for enrolled subjects 
with at least one laboratory assessment of grade 3 or 4 abnormality or a positive pregnancy test 
result: hematology; serum chemistry (including eGFR derived using MDRD); urinalysis. If there 
 
character value, or (2) numeric value 25 U/L. The listing will also include all pregnancy test 
results over time. 
 
In addition, a by-subject listing values and ratios to ULN (i.e., ALT, AST, TBL and ALP) will 
also be provided for enrolled subjects with select elevations (ALT or AST > 3 x ULN; ALP or 
TBL > 2 x ULN) at any time point. Refer to the Core SAP for listing content. 
6.4.2.1 
Laboratory Test Abnormalities 
Frequency tables of laboratory test abnormalities are provided for the following endpoints: 
 
Worst laboratory test abnormality for each graded laboratory test. 
 
Laboratory test toxicity grade shift from baseline to the worst toxicity grade for each 
graded laboratory test 
These 2 frequency tables are provided for the following analysis periods and analysis sets: 
 
On-DBT for the DBT treated analysis set 
o Summarized by rimegepant pooled, placebo pooled, and overall 
 
On-OL rimegepant for the OL rimegepant treated analysis set 
 
On-DB or OL rimegepant for the DB or OL rimegepant treated analysis set. 
Worst laboratory test abnormality will also be provided for the following analysis periods and 
analysis sets: 
 
Follow-up for the follow-up treated analysis set. 
 
6.4.2.2 
LFT Elevations 
Subjects must have non-missing LFT data (i.e., ALT, AST, TBL, or ALP) post-baseline to be 
included. 
Refer to the Core SAP for additional details. 
LFT Elevations: Cumulative, Mutually Exclusive, and Composite 
Frequency tables of LFT elevations are provided for the following safety analysis periods and 
analysis sets: 
 
Pretreatment for the DBT treated analysis set 
 
On-DBT for the DBT treated analysis set 
On-OL rimegepant for the OL rimegepant treated analysis set 
On-DB or OL rimegepant for the DB or OL rimegepant treated analysis set 


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Follow-up for the follow-up treated analysis set. 
LFT ULN Shifts from Baseline to Worst Elevation 
Frequency tables of LFT ULN shifts from baseline to the worst (highest) LFT elevation are 
provided for the following safety analysis periods and analysis sets: 
 
On-DBT for the DBT treated analysis set 
o Summarized by rimegepant pooled, placebo pooled, and overall 
 
On-DB or OL rimegepant for the DB or OL rimegepant treated analysis set where shifts 
are based on DB or OL rimegepant baseline. 
eDISH Scatter Plots 
Evaluation of drug-induced serious hepatotoxicity (eDISH) scatter plots are provided for the 
following safety analysis periods and analysis sets: 
 
On-DBT for the DBT treated analysis set with paired ALT and TBL ratios on DBT by 
treatment group 
 
On-OL rimegepant for the OL rimegepant treated analysis set with paired ALT and TBL 
ratios on OL rimegepant 
 
On-DB or OL rimegepant for the DB or OL rimegepant treated analysis set with paired 
ALT and TBL ratios on DB or OL rimegepant. 
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 day of the laboratory test result (x-axis) for treated subjects with any of the 
following LFT elevations post-baseline: ALT > 3 x ULN, AST > 3 x ULN, TBL > 2 x ULN, or 
ALP > 2 x ULN. Each figure also displays additional study milestones (e.g., start of the on-DBT 
treated analysis period, start of the OL rimegepant safety analysis period, and start of the follow- 
up period) using vertical lines with their corresponding descriptions in footnotes. 
6.4.2.3 
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 at each scheduled visit. 
The table of values and changes from baseline in hematology and serum chemistry laboratory 
tests is provided by rimegepant pooled, placebo pooled, and overall for the treated analysis set at 
the following time points: baseline; Day 35 in the on-DBT safety analysis period; and the 2-week 
follow-up safety visit. 
The table of values and changes from DB or OL rimegepant baseline in all hematology and 
serum chemistry laboratory tests is provided analogously for the DB or OL rimegepant treated 
analysis set at the following time points: DB or OL rimegepant baseline; Day 35 in the on-DBT 


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safety analysis period; each scheduled visit from Day 63 through Day 119 and EOT in the on-OL 
rimegepant safety analysis period; and the 2-week follow-up safety visit. 
Refer to the Core SAP for handling multiple values in an analysis visit window or on the same 
laboratory collection date, and deriving the EOT value in an on-treatment safety analysis period. 
6.4.3 
Vital Signs and Physical Measurements 
Vital signs and physical measurements will be measured at the following visits: Screening, 
Baseline (Day 1), Day 14, Day 21, Day 35, Day 63, Day 91, Day 119/EOT, and 2-week follow- 
up safety visit . 
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 height, weight and BMI. 
6.4.3.1 
Vital Signs and Physical Measurements Changes From Baseline Over 
Time 
Values and changes from baseline in vital sign and physical measurement parameters will be 
summarized as continuous parameters at each scheduled visit. 
The table of values and changes from baseline in vital signs and physical measurements is 
provided by rimegepant pooled, placebo pooled, and overall for the DBT treated analysis set at 
the following time points: baseline; each scheduled visit through Day 35 in the on-DBT safety 
analysis period; 2-week follow-up safety visit. 
The table of values and changes from DB or OL rimegepant baseline in vital sign and physical 
measurement parameters is provided analogously for the DB or OL rimegepant treated analysis 
set at the following time points: DB or OL rimegepant baseline; each scheduled visit through 
Day 35 in the on-DBT safety analysis period; each scheduled visit from Day 63 through Day 119 
and EOT in the on-OL rimegepant safety analysis period; and 2-week follow-up safety visit. 
Refer to the Core SAP for handling multiple values in an analysis visit window or on the same 
measurement date, and deriving the EOT value in an on-treatment safety analysis period. 
6.4.3.2 
Vital Signs and Physical Measurement Abnormalities 
Frequency tables of vital sign and physical measurement abnormalities are provided for the 
following safety analysis periods and analysis sets: 
 
On-DBT for the DBT treated analysis set 
o Summarized by rimegepant pooled, placebo pooled, and overall 
 
On-OL rimegepant for the OL rimegepant treated analysis set using OL rimegepant 
baseline 
 
On-DB or OL rimegepant for the DB or OL rimegepant treated analysis set using DB or 
OL rimegepant baseline 


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Follow-up for the follow-up treated analysis set. 
6.4.4 
Electrocardiograms 
12-Lead ECGs data will not be analyzed for the CSR. 
6.4.5 
Sheehan-Suicidality Tracking Scale (S-STS) 
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 
(Day 1), Day 14, Day 21, Day 35, Day 63, Day 91, Day 119/EOT, and 2-week follow-up safety 
visit. 
S-STS scores are calculated as described in the 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 by rimegepant pooled, placebo pooled 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) will also be presented by rimegepant pooled, 
placebo pooled 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-OL rimegepant for OL rimegepant treated subject; (3) on-DB or 
OL rimegepant for DB or OL rimegepant treated subjects, using DB or OL rimegepant baseline; 
and (4) follow-up for follow-up treated subjects. 
6.4.6 
Concomitant Procedures 
The by-subject listing of procedures is provided for the enrolled analysis set, and is based on the 
Concomitant Procedures CRF. Procedures are coded in MedDRA. Refer to the Core SAP for 
additional details. 
6.4.7 
Covid-19 Impact 
Covid-19 impact will not be assessed for this CSR. 
6.5 
Pharmacokinetics 
PK will not be analyzed for this CSR. 
7 CONVENTIONS 
7.1 
General 
7.1.1 
Output Layout 
Refer to the Core SAP for TLF layout conventions. 


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For the final analysis of the DBT phase and the final analysis after the OLE phase, a list of TLFs 
and unique TLF templates will be provided in the Mock TLF document. 
7.2 
Analysis Periods 
Analysis periods are defined as follows: 
 
Efficacy endpoints 
o On-DBT efficacy: This period is used to assess efficacy during the DBT Phase, and is 
 in the efficacy listing. 
o On-OL rimegepant efficacy: 
 
the efficacy listing. 
o Follow-up efficacy: 
 
Pretreatment characteristics and safety endpoints 
o Pretreatment: 
 is used to derive 
baseline values and to assess pretreatment safety endpoints. 
o Pre-OL rimegepant: This period is used to derive the OL rimegepant baseline value. 
o Pre-DB or OL rimegepant: This period is used to derive the DB or OL rimegepant 
baseline value. 
o On-DBT safety: 
 
assess safety endpoints on DBT for the DBT treated analysis set 
o Post-DBT pre-OL rimegepant safety: 
 
listings, and is used to assess safety endpoints during the interim period (i.e., post-DBT 
pre-OL rimegepant) for the interim treated analysis set. 
o On-OL rimegepant safety 
RMG
 
is used to assess safety endpoints for the OL rimegepant treated analysis set. 
o On-DB or OL rimegepant safety: This period is used to assess safety endpoints on DB or 
OL rimegepant treatment for the DB or OL rimegepant treated analysis set 
o Follow-up safety: 
y listings, and is used to 
assess safety endpoints during follow-up. 
 
Outcomes research endpoints 
o DBT outcomes research: 
 
listings, and used to assess outcomes research endpoints during the DBT Phase 
o OL rimegepant outcomes research 
 
research listings, and used to assess outcomes research endpoints during the OLE Phase. 
 
 defined as the Day 14 
CRF visit, analysis period 2 is defined as the Day 35 or Day 35/ET CRF visit. 


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-on-
 
 
For AEs, refer to Section 6.4.1 for analysis period definitions. 
 
For NPRS endpoints, analysis period 1 is defined as the Day 14 visit, analysis period 2 is 
defined as the Day 35 or Day 35/ET visit, with visits derived using treatment exposure 
start and end dates. 
8 CONTENT OF REPORTS 
The final CSR is planned after the last planned analysis. 
All analyses described in this SAP are included. 
9 APPENDICES 
9.1 
Relevant Protocol Deviations 
 
Relevant eligibility protocol deviations include the following categories: 
 
 NPRS during the last 14 days 
in the Screening Period 
TN onset less than 3 months prior to Screening 
Classical TN not confirmed on neuroimaging 
Neurological examination not done or incomplete (i.e., cranial, facial, or trigeminal nerve 
assessment not done) 
Non-compliance with or inability to complete the paper diary during the Screening 
Period. Non-compliance is 2 or more missed evening reports during the Screening Phase. 
Subjects should be considered for discontinuation after discussion with the sponsor. 
Medical history, defined as any of the following subcategories: 
o Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), 
Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient 
focal neurological deficit during the 6 months prior to screening 
o 
 
o Gastric or small intestinal surgery. 
Finding out of range during the pretreatment period or Day 35 if entering OL phase, defined as 
any of the following: 
ALT/AST/Direct Bilirubin/Indirect Bilirubin/Total Bilirubin > 1 xULN 
GGT > 1.5 xULN 
ECG abnormalities as follows: 


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o Corrected QT interval > 470 msec (QTc by method of Frederica) 
o Left Bundle Branch block 
o Right Bundle Branch Block with a QRS duration  150 msec 
 
o Intraventricular Conduction Defect with a QRS duration  150 msec 
 
Neutrophil count  
 
 
HbA1c  8% 
 
Diastolic measurement of 96mmHg 
 
 
Estimated glomerular filtration rate (eGFR) according to the re-expressed abbreviated (4- 
variable) Modification of Diet in Renal Disease (MDRD) Study equation  40 
mL/min/1.73m2 
 
BMI  33 kg/m2 
 
Positive for cocaine or PCPs at any visit 
 
Females with a positive pregnancy test at any visit 
 
 
 is   
 
on the Sheehan Suicidality Tracking Scale at any visit 
 
Relevant subject management protocol deviations include the following: 
Type of TN discrepant between IWRS and CRF data, defined as any of the following 
subcategories: 
o 
 
(Demographics page) 
o 
 
(Demographics page) 
Prohibited non-study medications, procedures, or therapies defined as any of the 
following: 
o Standard of care Trigeminal Neuralgia medications with dose change or with start 
date < 4 weeks prior to randomization (see Section 4.4.1 for the definition of 
standard of care Trigeminal Neuralgia medication) 
o Carbamazepine taken during the Screening Period or afterward 


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o Barbiturate-containing products (e.g. Fioricet, Fiorinal, butalbital, phenobarbital) 
taken up to 14 days prior to the Baseline Visit (randomization) or afterward 
o Modafinil (PROVIGIL®) taken up to 14 days prior to the Baseline Visit 
(randomization) or afterward 
o Butterbur root or extracts taken up to 14 days prior to the Baseline Visit 
(randomization) or afterward 
o Ergotamine medications taken on  10 days per month on a regular basis for  3 
months 
o Narcotic medication, such as opioids, taken up to 2 days prior to the Baseline 
Visit or afterward 
o Acetaminophen or acetaminophen containing products taken within 2 days before 
randomization. 
o Use of acetaminophen during the Screening Period (3 to 14 days) or throughout 
the study at daily dosing levels of greater than 1000 mg/day 
o Muscle relaxants (except baclofen) taken during the Screening Period or 
throughout the study 
o Baclofen with start date < 8 weeks prior to randomization 
o Strong CYP3A4 inhibitors taken during the Screening Period or throughout the 
study 
o Strong CYP3A4 inducers taken during the Screening Period or throughout the 
study 
o Strong inhibitors of the P-gp transporter taken during the Screening Period or 
throughout the study 
o CGRP antagonists (biologic or small molecule) taken during the Screening Period 
or throughout the study 
Note: Medications taken up to X days before a reference date or afterward are defined 
as those with medication start date or stop date  reference date  X. Refer to the 
Core SAP for additional details about prohibited non-study medications. 
o 
afterward 


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DB study drug dosing issue, defined as any of the following subcategories (see Section 
6.2.6): 
o DB study drug taken but not randomized 
o DB tablet count compliance < 80% from DB study drug start to later of last 
scheduled DBT Phase visit or DB study drug end 
o > 1 DB tablet taken on any 1 day 
o Incorrect DB study drug taken 
OLE rimegepant dosing issue, defined as any of the following subcategories (see Section 
6.2.6): 
o OLE rimegepant tablet count compliance < 80% from OL rimegepant start to later 
of last scheduled OLE Phase visit or OL rimegepant end 
o > 1 OLE rimegepant tablet taken on any 1 day 


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10 REFERENCES 
Not applicable.