Clinical trial NCT05264129
Conditions: Episodic Migraine
Keywords: Episodic Migraine Ubrogepant Atogepant QULIPTA UBRELVY
Sponsor: AbbVie
Start date: 2022-03-07; Completion date: 2023-04-04
Enrollment: 263 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Migraine is a neurological disease characterized by moderate or severe headache, associated with nausea, vomiting, and/or sensitivity to light and sound. This study will assess the safety and efficacy of the combination use of ubrogepant for the acute treatment of migraine headache in participants taking atogepant once daily for preventive treatment of migraine.

Ubrogepant is an approved drug for the acute treatment of migraine. Atogepant is an approved drug for the preventive treatment of migraine. Approximately 235 adult participants with EM will be enrolled in approximately 45 sites in the United States.

Participants will receive oral atogepant tablets once daily (QD) for 12 weeks followed by continued atogepant treatment with ubrogepant tablets taken as needed for the next 12 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Detailed description:

Arms: arm 1: Participants will receive atogepant for 12 weeks followed by atogepant + ubrogepant for 12 weeks.
Interventions: intervention 1: Atogepant intervention 2: Ubrogepant
Intervention descriptions: intervention 1: Oral Tablet intervention 2: Oral Tablet

Protocol documents:
Prot_000.pdf: 


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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
7
2.1
BACKGROUND AND RATIONALE
7
2.2
BENEFITS AND RISKS TO SUBJECTS
7
3
OBJECTIVES AND ENDPOINTS
8
3.1
OBJECTIVES, HYPOTHESES, AND ESTIMANDS
8
3.2
PRIMARY ENDPOINT
8
3.3
EXPLORATORY EFFICACY ENDPOINTS
8
3.4
SAFETY ENDPOINTS
9
3.5
PHARMACOKINETIC ENDPOINTS
9
3.6
BIOMARKER RESEARCH ENDPOINTS
9
4
INVESTIGATIONAL PLAN
10
4.1
OVERALL STUDY DESIGN AND PLAN
10
4.2
DISCUSSION OF STUDY DESIGN
11
5
STUDY ACTIVITIES
12
5.1
ELIGIBILITY CRITERIA
12
5.2
CONTRACEPTION RECOMMENDATIONS
16
5.3
PROHIBITED MEDICATIONS AND THERAPY
17
5.4
PRIOR AND CONCOMITANT THERAPY
18
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
20
5.6
FOLLOW-UP AFTER SUBJECT DISCONTINUATION OF STUDY DRUG OR FROM STUDY
21
5.7
STUDY DRUGS
21
5.8
RANDOMIZATION/DRUG ASSIGNMENT
22
5.9
PROTOCOL DEVIATIONS
22
5.10 DATA MONITORING COMMITTEE AND HEPATIC EVENT ADJUDICATION COMMITTEE
22
6
SAFETY CONSIDERATIONS
23
6.1
COMPLAINTS AND ADVERSE EVENTS
23
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7
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE
27
7.1
STATISTICAL AND ANALYTICAL PLANS
27
7.2
DEFINITION FOR ANALYSIS POPULATIONS
27
7.3
HANDLING POTENTIAL INTERCURRENT EVENTS FOR THE PRIMARY AND EXPLORATORY ENDPOINTS
27
7.4
STATISTICAL ANALYSES FOR EFFICACY
27
7.5
STATISTICAL ANALYSES FOR SAFETY
28
7.6
INTERIM ANALYSIS
28
7.7
OVERALL TYPE I ERROR CONTROL
28
7.8
SAMPLE SIZE DETERMINATION
28
8
ETHICS
29
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD
29
8.2
ETHICAL CONDUCT OF THE STUDY
29
8.3
SUBJECT CONFIDENTIALITY
29
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
29
10 DATA QUALITY ASSURANCE
29
11 START AND COMPLETION OF THE STUDY
29
12 REFERENCES
30
LIST OF TABLES
TABLE 1.
STUDY DRUGS
22
LIST OF FIGURES
FIGURE 1.
STUDY DESIGN
11
LIST OF APPENDICES
APPENDIX A.
STUDY-SPECIFIC ABBREVIATIONS AND TERMS
31
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
33
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APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
34
APPENDIX D.
ACTIVITY SCHEDULE
35
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
37
APPENDIX F.
OPERATIONS MANUAL
40
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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted?
A proportion of individuals receiving preventive monotherapy for migraine may continue to experience 
migraine attacks and migraine-related disability.1,2 A large body of evidence suggests that calcitonin 
gene-related peptide (CGRP) plays a central role in the pathogenesis of migraine.3,4,5  CGRP levels in the 
cranial circulation are increased during a migraine attack and CGRP itself has been shown to trigger 
migraine-like headache.
Atogepant is an orally active CGRP receptor antagonist. Atogepant has demonstrated efficacy in 
significantly reducing the number of migraine and headache days in patients with episodic migraine 
(EM) and was recently approved by the Food and Drug Administration (FDA) for the preventive 
treatment of EM in adults. Ubrogepant is another potent, selective, orally active, CGRP receptor 
antagonist that has been approved by the FDA for the acute treatment of migraine with or without aura 
in adults.
Both drugs have been shown to be safe and well tolerated.  Ubrogepant is similar in structure and 
mechanism of action to atogepant and the additive effect of combination therapy is currently unknown.  
This open-label study is being conducted to evaluate the safety, tolerability, and efficacy of the 
concomitant use of ubrogepant for the acute treatment of breakthrough migraine headache in subjects 
taking atogepant once daily for the preventive treatment of EM.
2.2 Benefits and Risks to Subjects
Atogepant was approved in 20216 by the FDA for the preventive treatment of episodic migraine in adults 
and ubrogepant was approved in 20197 for the acute treatment of migraine in adults.  Efficacy was 
demonstrated in the respective pivotal studies.  Both drugs have shown to be safe and well tolerated.  
Atogepant and ubrogepant have very similar mechanisms of action; therefore, no additional safety risk 
is expected from concomitant use.  An independent Data Monitoring Committee (DMC) will review 
safety data throughout the study and make recommendations to the sponsor including modification or 
early termination of the study.  Considering the measures taken to minimize risk to subjects 
participating in this study, the potential risks identified in association with atogepant and ubrogepant 
are justified by the anticipated benefits that may be afforded to subjects with migraine.  Overall, the 
benefit risk assessment is favorable.
For further details, please see findings from completed studies, including safety data in the current 
atogepant and ubrogepant Investigator's Brochures (IBs).4,5
Considering the coronavirus – 2019 (COVID-19) pandemic, the benefit and risk to subjects participating 
in migraine studies testing these compounds have been evaluated. Based on the limited information to 
date, no additional risk to study subjects is anticipated with the use of atogepant and ubrogepant. 
Currently, there is no data to suggest that these drugs interfere with the functioning of the immune 
system and, therefore, an increased risk is not expected.
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3 OBJECTIVES AND ENDPOINTS
3.1 Objectives, Hypotheses, and Estimands
Primary

To evaluate the safety and tolerability of the concomitant use of ubrogepant 100 mg for the 
acute treatment of breakthrough migraine headache in subjects taking atogepant 60 mg once 
daily for preventive treatment of EM.
Exploratory

To evaluate the clinical benefit of the concomitant use of ubrogepant 100 mg, taken as needed, 
and atogepant 60 mg once daily in subjects with EM.

To explore the efficacy of ubrogepant 100 mg, taken as needed, for the acute treatment of 
migraine in subjects taking atogepant 60 mg once daily for preventive treatment of EM.
3.2 Primary Endpoint
The endpoint is to assess the safety and tolerability (see Section 3.4) of atogepant and ubrogepant 
administered concomitantly.
3.3 Exploratory Efficacy Endpoints
Exploratory efficacy endpoints are as follows:

Change from baseline in mean monthly migraine days, headache days, and acute medication 
use days across Weeks 1 to 12, Weeks 13 to 24), and at each 4-week interval.

25%, 50%, 75%, and 100% reduction in mean monthly migraine days across Weeks 1 to 12, 
Weeks 13 to 24, and at each 4-week interval. 

Percentage of migraine attacks treated with ubrogepant that result in pain freedom at 2 hours, 
pain relief at 2 hours, sustained pain freedom from 2 to 24 hours, and sustained pain relief from 
2 to 24 hours across Weeks 13 to 24 and at each 4-week interval. 

Patient satisfaction with atogepant at Week 12 and Week 24.

Patient satisfaction with ubrogepant, taken as needed, at Week 24.

Patient satisfaction with the concomitant use of atogepant and ubrogepant (taken as needed) at 
Week 24.

Change from baseline in the Headache Impact Test (HIT)-6 total score at Weeks 4, 8, 12, 16, 20, 
and 24.

At least a 5-point improvement (decrease) from baseline in HIT-6 total score at Weeks 4, 8, 12, 
16, 20, and 24.
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
Patient Global Impression of Change (PGIC) of "much better" or "very much better" at Week 12 
(atogepant) and Week 24 (atogepant + ubrogepant).

Change from baseline in percent work time missed, percent impairment while working, percent 
overall impairment, and percent activity impairment due to migraine at Weeks 4, 8, 12, 16, 20, 
and 24) as assessed by the Work Productivity and Activity Impairment Questionnaire:Migraine 
(WPAI:MIGRAINE).

Change from baseline in the Migraine-Specific Quality-of-Life Questionnaire (MSQ) v2.1 Role 
Function-Preventive domain score at Weeks 4, 8, 12, 16, 20, and 24.

Change from baseline in the MSQ v2.1 Role Function-Restrictive domain score at Weeks 4, 8, 12, 
16, 20, and 24.

Change from baseline in the MSQ v2.1 Emotional Function domain score at Weeks 4, 8, 12, 16, 
20, and 24.

Change from baseline in the Patient Health Questionnaire (PHQ)-4 score at Weeks 4, 8, 12, 16, 
20, and 24.

Migraine Treatment Optimization Questionnaire (MTOQ)-6 score at Weeks 16, 20, and 24.
3.4 Safety Endpoints
Safety evaluations include adverse event (AE) monitoring, vital sign measurements, electrocardiogram 
(ECG) variables, clinical laboratory testing (hematology, chemistry, and urinalysis), and Columbia Suicide 
Severity Rating Scale (C-SSRS) as measures of safety and tolerability for the entire study duration.
3.5 Pharmacokinetic Endpoints
Plasma atogepant and ubrogepant concentrations will be obtained at the respective visits, as indicated
in the Schedule of Activities (Appendix D).  PK sample collection is optional.  A nonlinear mixed-effects 
modeling approach will be used to estimate the population central values and the empirical Bayesian 
estimates of the individual values of atogepant and ubrogepant oral clearance (CL/F) and volume of 
distribution (V/F).  Additional parameters may be estimated if useful in the interpretation of the data.
The results of population PK analyses may not be included with the clinical study report.
3.6 Biomarker Research Endpoints
Biomarkers
Biospecimens (plasma and saliva) will be collected at specified time points (Appendix D) during the study 
to evaluate known and/or novel disease-related or drug-related biomarkers in circulation or at tissue 
sites. Sample collection is optional.  The analyses may include but are not limited to: biomarkers 
associated with mechanisms of migraine, such as calcitonin gene-related peptide (CGRP) and its 
degradants. This research may be exploratory in nature and the results may not be included with the 
clinical study report. Further details regarding the biomarker research rationale and collection time 
points are located in the Operations Manual, Section 3.6 and Appendix F.
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Pharmacogenetics
DNA isolated from whole blood (pharmacogenetic sample) will be collected at Screening (Visit 1).  
Sample collection is optional.  DNA may be analyzed to determine specific genetic mutations in subjects 
with migraine and related conditions, as well as determine if any of these mutations are associated with 
response to treatment with atogepant or ubrogepant (or drugs of this class).  Further details regarding 
the pharmacogenetic research rationale and collection time point are located in the Operations Manual, 
Section 3.6 and Appendix F.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a multicenter, open-label, Phase 4 study conducted in the United States (US) to evaluate the 
safety, tolerability, and efficacy of the concomitant use of ubrogepant 100 mg for the acute treatment of 
breakthrough migraine headache in subjects taking atogepant 60 mg once daily for preventive 
treatment of EM.
Subject participation will begin with up to a 1 week screening period.  Subjects who continue to meet all 
entry criteria at Baseline/Visit 2 (Day 1) will be assigned atogepant 60 mg once daily for the preventive 
treatment of migraine.
Screen failures are defined as subjects who consent to participate in the study, however, are not 
subsequently assigned to receive study drug.  Rescreening of screen failures is permitted in certain 
situations, with permission from the Sponsor, however, subjects with exclusionary laboratory values at 
Visit 1 (including alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 1 x upper limit of 
normal [ULN], total bilirubin > 1 × ULN, or serum albumin < 2.8 g/dL) are not allowed to be rescreened
(note that total bilirubin > 1 × ULN in subjects with Gilbert's disease is not exclusionary).
The open-label atogepant treatment period will last for 12 weeks (Visits 2-5). During this study period, 
subjects will use their usual medications for the acute treatment of breakthrough migraine headaches.  
At Visit 5, subjects who complete the open-label atogepant treatment period will continue into the 
open-label atogepant + ubrogepant concomitant use period which will last for an additional 12 weeks 
(Visits 5 to 8). During this study period, subjects will continue to take atogepant 60 mg once daily and 
will also be provided ubrogepant 100 mg to treat up to 8 breakthrough migraine headaches of any pain 
intensity per 4-week visit interval. During this time, subjects will take a dose of ubrogepant 100 mg to 
treat their breakthrough migraine headache.  If after 2 hours, the migraine attack has not resolved or 
the migraine headache returns within 24 hours, subjects can choose either to take a second dose of 
ubrogepant 100 mg or any of the acute medications listed in Section 5.4.
There will be a total of 9 scheduled clinic visits: Screening/Visit 1 (Week -1), Baseline/Visit 2 (Day 1), 
Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8/Early 
Termination (Week 24), and Visit 9/Safety Follow-up (Week 28).
The total duration of study participation is 29 weeks.  Total treatment duration is 24 weeks.  See 
Section 5 for information regarding eligibility criteria.
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All subjects who take at least 1 dose of atogepant 60 mg will enter a safety follow-up period of 
4 additional weeks after their last dose of study drug.  All subjects, regardless of the number of doses of 
study drug which are self-administered, should complete Visit 8/Early Termination and Visit 9 (Safety 
Follow-up), unless the subject has withdrawn consent.  An interim analysis that includes all safety and 
efficacy analyses is planned.  Details are provided in Section 7.6.
The schematic of the study is shown in Figure 1.  Further details regarding study procedures are located 
in the Operations Manual (Appendix F).
Figure 1.
Study Design
4.2 Discussion of Study Design
Choice of Control Group
Not applicable.
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All efficacy and 
safety-related measurements in this study are standard for assessing disease activity in subjects with 
migraine.  All clinical and laboratory procedures in this study are standard and generally accepted.
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Clinical Hypotheses
The concomitant use of ubrogepant for acute treatment and atogepant for preventive treatment of 
migraine will be well tolerated and have an acceptable safety profile. 
The concomitant use of ubrogepant 100 mg taken as needed and atogepant 60 mg once daily provides 
substantial clinical benefit in subjects with EM.
Ubrogepant 100 mg taken as needed is effective for the acute treatment of migraine in subjects taking 
atogepant 60 mg once daily for preventive treatment of EM.
Suitability of Subject Population
Individuals receiving preventive monotherapy for migraine may continue to experience migraine attacks 
and migraine-related disability. Subjects taking the highest approved doses of atogepant (60 mg once 
daily) for the preventive treatment of EM are well suited to receive ubrogepant for the acute treatment 
of migraine headache of moderate/severe intensity when breakthrough migraine attacks occur while on 
atogepant.
Selection of Doses in the Study
The approved doses for ubrogepant are 50 or 100 mg taken once or twice for the acute treatment of 
migraine within a 24-hour period.  The approved doses for atogepant are 10, 30, or 60 mg once daily for 
the preventive treatment of EM.  For this study, the highest approved doses (60 and 100 mg, 
respectively) were selected to evaluate the safety and tolerability of the concomitant use of atogepant 
and ubrogepant.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.  Anything other than 
a positive response to the questions below will result in exclusion from study participation.
Consent
1. Subjects must voluntarily sign and date an informed consent, approved by an independent 
ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or 
study-specific procedures.
Demographic and Laboratory Assessments
2. Male or female subjects ages 18 to 80 years, inclusive, at Visit 1.
3. Must not have clinically significant laboratory values OR any of the following criteria at 
Visit 1:

ALT or AST > 1 × ULN;

total bilirubin > 1 × ULN (except for subjects with a diagnosis of Gilbert's disease); OR
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
serum albumin < 2.8 g/dL.
4. Are willing and able to comply with procedures required in this protocol.
Disease/Condition Activity
5. At least a 1-year history of migraine with or without aura consistent with a diagnosis 
according to the International Classification of Headache Disorders (ICHD)-3, 2018. (See
Section 7.1 of the Operations Manual).
6. Age of the subject at the time of migraine onset < 50 years.
7. History of 4 to 14 migraine days per month (see Section 3.4 of the Operations Manual for 
definition of migraine day) on average in the 3 months prior to Screening/Visit 1 in the 
investigator's judgment.
8. History of less than 15 headache days per month (see Section 3.4 of the Operations Manual 
for definition of headache day) on average across the 3 months prior to Screening/Visit 1 in the 
investigator's judgment.
9. Able to distinguish migraine headaches from tension-type or other headaches.
Subject History
10. No history of migraine accompanied by diplopia or decreased level of consciousness or 
retinal migraine as defined by ICHD-3, 2018. (See Section 7.1 of the Operations Manual)
11. No current diagnosis of chronic migraine, new persistent daily headache, trigeminal 
autonomic cephalgia (e.g., cluster headache), or painful cranial neuropathy as defined by 
ICHD-3, 2018.
12. For subjects who have taken 5 or more preventive medications for migraine with proven 
efficacy in the past, no history of an inadequate response to 5 or more prescription prevention 
medications in 2 or more different mechanisms of action (see Section 7.3 of the Operations 
Manual for list of preventive treatments for migraine with proven efficacy and 
failure/inadequate response definitions).
13. No ECG with clinically significant abnormalities at Screening/Visit 1 as determined by the 
investigator.
14. No clinically significant cardiovascular or cerebrovascular disease per the investigator's 
judgment including, but not limited to:

Clinically significant ischemic heart disease (e.g., unstable angina pectoris)

Clinically significant cardiac rhythm or conduction abnormalities (e.g., atrial fibrillation, 
second- or third-degree heart block) or risk factors for Torsade de Pointes (e.g., heart 
failure, hypokalemia, bradycardia)

Myocardial infarction, transient ischemic attack, or stroke within 6 months prior to 
Screening/Visit 1
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
Heart failure defined as Class III or IV by the New York Heart Association functional 
classification system
15. No hypertension as defined by sitting systolic blood pressure > 160 mm Hg or sitting diastolic 
blood pressure > 100 mm Hg at Screening/Visit 1 or Baseline/Visit 2.  Vital sign measurements 
that exceed these limits may be repeated only once at each visit.
16. No clinically significant hematologic, endocrine, pulmonary, renal, hepatic, neurologic, or 
gastrointestinal disease:

If there is a history of such a disease, but the condition has been stable for more than 1 year 
prior to Screening/Visit 1, and is judged by the investigator as not likely to interfere with the 
subject's participation in the study, the subject may be included

Subjects on dialysis are not eligible to participate
17. No known history of chronic liver disease (including nonalcoholic fatty liver disease, viral 
chronic hepatitis, and cirrhosis); or a positive result on hepatitis B surface antigen or 
anti-hepatitis C antibody testing at Screening/Visit 1; no history of acute hepatitis within 
6 months of Screening/Visit 1.
18. No known active SARS-CoV-2 infection.  If a subject has signs/symptoms suggestive of 
SARS-CoV-2 infection, the subject must have a negative molecular (e.g., polymerase chain 
reaction [PCR]) test result.  Note:  SARS CoV-2 diagnostic tests should be applied following local 
requirements/recommendations.
19. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and 
may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:

At least 14 days since the first PCR test result has passed in asymptomatic subjects or 
14 days since recovery, defined as resolution of fever without use of antipyretics and 
improvement in symptoms.
20. No unremitting symptoms of "long COVID" due to prior SARS-CoV-2 infection or any other
lasting symptoms that, in the investigator's judgment, may put the participant at significant risk
or, may confound the study results.
21. In the judgment of the investigator, no confounding psychiatric conditions, dementia, 
epilepsy, or significant neurological disorders other than migraine.
22. No other concurrent pain condition that, in the judgment of the investigator, may 
significantly impact the current headache disorder (e.g., fibromyalgia, facial pain).
23. No significant risk of self-harm based on clinical interview and responses on the C-SSRS or of 
harm to others in the judgment of the investigator; subjects must be excluded if they report 
suicidal ideation with intent, with or without a plan, (i.e., Type 4 or 5 on the C-SSRS) in the past 
6 months or report suicidal behavior in the 6 months prior to Screening/Visit 1 or at 
Baseline/Visit 2 assessments.
24. No history of malignancy in the 5 years prior to Screening/Visit 1, except for adequately 
treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
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25. No history of any gastrointestinal (GI) prior procedures or GI conditions (e.g., diarrhea 
syndromes, inflammatory bowel disease) that may affect the absorption or metabolism of study 
intervention; subjects with prior gastric bariatric interventions (e.g., Lap Band) which have been 
reversed are not excluded.
26. At Screening/Visit 1, subject is not a user of illegal drugs and has no history within the past 
year of drug or alcohol abuse or dependence per investigator judgment.
27. No history of hypersensitivity or clinically significant adverse reaction to a CGRP receptor 
antagonist.
28. Not employed by or is an immediate family member (parents, spouses, siblings, or children) 
of one of the investigators, study staff, or AbbVie.
29. No conditions or current situations which in the investigator's judgment may put the subject
at significant risk, may confound the study results, or may interfere significantly with the 
subject's participation in the study.
30. No medical or other reasons (e.g., unlikely to adhere to the study procedures, keep 
appointments, or is planning to relocate during the study) that, in the investigator's judgment, 
might indicate that the subject is unsuitable for the study.
Contraception (See also Section 5.2 Contraception Requirements)
31. For all females of childbearing potential; a negative urine pregnancy test at the 
Screening/Visit 1 and a negative urine pregnancy test at Baseline/Visit 2 prior to the first dose of 
study drug.
32. Female subjects of childbearing potential must agree to practice at least 1 protocol-specified 
method of birth control, that is effective from Baseline/Visit 2 (Day 1) through at least 30 days 
after the last dose of study drug.  Female subjects of nonchildbearing potential do not need to 
use birth control.
33. Female who is not pregnant or breastfeeding and is not considering becoming pregnant or 
donating eggs during the study or for approximately 30 days after the last dose of the study 
drug.
34. For male subjects with sexually active female partner(s) of childbearing potential, he must 
agree, from Baseline/Visit 2 (Day 1) through 30 days after the last dose of study drug, to practice 
the protocol-specified contraception.
35. Male who is not considering fathering a child or donating sperm during the study or for 
approximately 30 days after the last dose of study drug.
Concomitant Medications
36. No requirement for any medication, diet (i.e., grapefruit juice), or nonpharmacological 
treatment that is on the list of prohibited concomitant medications or treatments that cannot 
be discontinued or switched to an allowable alternative medication or treatment (See 
Protocol Section 5.3 Prohibited Medications and Therapy and Section 7.2 of Operations 
Manual).
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
This includes no requirement for the use of concomitant medications with demonstrated 
efficacy for the prevention of migraine (e.g., amitriptyline, topiramate, propranolol) for any 
reason (e.g., hypertension).  
37. No previous exposure to atogepant; no exposure to injectable monoclonal antibodies 
blocking the CGRP pathway within the last 6 months; no exposure to rimegepant for preventive 
treatment of migraine within the last 1 month.
38. Not currently participating in or has not participated in a study with an investigational 
compound or device within 30 days prior to Screening/Visit 1 (this includes studies using 
marketed compounds or devices).
39. No usage of opioids > 4 days/month in the 3 months prior to Screening/Visit 1 per 
investigator's judgment.
5.2 Contraception Recommendations
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified:

Females, Nonchildbearing Potential
Females do not need to use birth control during or following study drug treatment if considered 
of nonchildbearing potential due to meeting any of the following criteria:
1.
Premenopausal female with permanent sterility or permanent infertility due to one of the 
following:

Permanent sterility due to a hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy.

Non-surgical permanent infertility due to Mullerian agenesis, androgen insensitivity, or 
gonadal dysgenesis; investigator discretion should be applied to determining study entry 
for these individuals.
2.
Postmenopausal female

Age > 55 years with no menses for 12 or more months without an alternative medical 
cause.

Age ≤ 55 years with no menses for 12 or more months without an alternative medical 
cause AND a follicle-stimulating hormone level > 30 IU/L.

Females, of Childbearing Potential

Combined (estrogen- and progestogen-containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation-initiated at 
study Baseline/Visit 2 (Day 1).

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at study Baseline/Visit 2 (Day 1).
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
Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).

Intrauterine device.

Intrauterine hormone-releasing system.

Vasectomized partner (provided the partner has received medical confirmation of the 
surgical success of the vasectomy and is the sole sexual partner of the study subject).

Practice true abstinence, defined as:  Refraining from heterosexual intercourse when
this is in line with the preferred and usual lifestyle of the subject (periodic abstinence 
[e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are 
not acceptable).
Contraception recommendations related to use of concomitant therapies prescribed should be based on 
the local label.
Contraception Requirements for Males
Male subjects who are sexually active with a female partner of childbearing potential, must agree to use 
male condoms, even if the male subject has undergone a successful vasectomy, from Baseline/Visit 2 
(Day 1) through at least 30 days after the last dose of study drug.
5.3 Prohibited Medications and Therapy
The following medications/treatments/therapies/lifestyle activities are prohibited 30 days prior to 
Screening/Visit 1 (unless otherwise indicated) and throughout the study. An extended list of examples 
of prohibited medications are displayed in Section 7.2 in the Operations Manual.

Medications with demonstrated efficacy for the prevention of migraine (e.g., amitriptyline, 
topiramate, propranolol) used to prevent migraine or for any indication (e.g., propranolol for 
hypertension is not allowable).  If the subject is on a routine prescription medication for 
migraine prevention and if the permissibility of a specific medication/treatment is in question, 
please contact the Therapeutic Area Medical Director.

Commercially available rimegepant (Nurtec™) is prohibited from Visits 1 to 9.  Commercially 
available ubrogepant (Ubrelvy™) is prohibited from Visits 1-9 (ubrogepant provided as study 
drug is allowed from Visits 5-8).

Injectable monoclonal antibodies blocking the CGRP pathway (e.g., Aimovig™, Emgality™, 
Ajovy®, Vyepti™) within 6 months prior to Screening/Visit 1 and throughout the study period.

Therapeutic or cosmetic botulinum toxin injections (e.g., Dysport®, BOTOX®, Xeomin®, 
Myobloc®, Jeuveau™) into areas of the head, face, or neck within 6 months prior to 
Screening/Visit 1 and throughout the study period.

Acupuncture, noninvasive neuromodulation devices (e.g., transcutaneous supraorbital 
neurostimulator, single-pulse transcranial magnetic stimulator, vagus nerve stimulator), cranial 
traction, nociceptive trigeminal inhibition, occipital nerve block treatments, or dental splints for 
headache.
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
Strong and moderate CYP3A4 inhibitors, including, but not limited to: systemic 
(oral/intravenous [IV]) boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, 
grapefruit juice, 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, telithromycin, troleandomycin, voriconazole, 
clarithromycin, idelalisib, nefazodone, nelfinavir, aprepitant, ciprofloxacin, conivaptan, 
crizotinib, cyclosporine, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, 
imatinib, tofisopam, and verapamil.

Strong and moderate CYP3A4 inducers, including but not limited to: apalutamide, 
carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort, bosentan, 
efavirenz, etravirine, phenobarbital, primidone.

Strong OATP1B1 inhibitors (e.g., gemfibrozil).

Drugs with narrow therapeutic margins with theoretical potential for CYP drug interactions 
(e.g., warfarin).

Cannabinoids (e.g., marijuana, tetrahydrocannabinol [THC] containing products) or ingested
cannabidiol (CBD) containing products.

Subjects should refrain from consuming grapefruit or grapefruit juice from the time the consent 
form is signed until completion of the study.  Participants should also refrain from making 
significant changes to their diet or caffeine intake during the study.

Alcohol intake should be limited to no more than 1 drink/day throughout the study.  A drink is 
defined as a 12-ounce can/bottle of beer, a 4-ounce glass of wine or 1 ounce of liquor.
The decision to administer a prohibited medication/treatment is done with the safety of the study 
subject as the primary consideration. Therapy considered necessary for the subject's welfare may be 
given at the discretion of the investigator. When possible, AbbVie should be notified before the 
prohibited medication/treatment is administered. If the permissibility of a specific 
medication/treatment is in question, please contact AbbVie.
Medications/vaccines that are not specifically prohibited are allowed, with the following clarifications 
and restrictions:

Aspirin up to 325 mg/day is allowed for cardiac prophylaxis (see Section 5.4 for non-steroidal 
anti-inflammatory drugs [NSAIDs] use for migraine).

Selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors
(SNRIs), except venlafaxine and desvenlafaxine, are permitted provided that treatment is stable 
for at least 60 days prior to Screening/Visit 1 and continues without change in dose throughout 
the study, and is not indicated for the treatment of migraine or headaches.
5.4 Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject is receiving at the time of enrollment or receives during the study 
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must be recorded from 6 months prior to Screening/Visit 1 (Day 1) through the Safety Follow-up/Visit 9
(Week 28). All prior and concomitant headache/migraine medications including migraine prevention
medications must be recorded.
Any questions regarding concomitant or prior therapy should be raised to the sponsor contact.  
Information regarding potential drug interactions with atogepant or ubrogepant can be located in the 
current atogepant or ubrogepant Investigator's Brochure.4,5
During the study, the following medications are allowed for the acute treatment of migraines as needed 
with no restrictions with the exception of opioid use.

Any triptan

Any ditan

Any ergot derivative

Any opioid (≤4 days/month)

Any other form of analgesic (including acetaminophen)

Any NSAID agent

Any antiemetic agent
During the open-label atogepant period (Visits 2-5 [Day 1 to Week 12]), any of the acute medications 
listed above may be taken for breakthrough migraine attacks.
During the open-label atogepant and ubrogepant concomitant use period (Visits 5-8 [Weeks 12 to 24]), 
ubrogepant 100 mg (provided as study drug by AbbVie) should be used as the acute treatment for all 
breakthrough migraine attacks. If after 2 hours, the migraine attack has not resolved or the migraine 
headache returns within 24 hours, subjects can choose either to take a second dose of ubrogepant 
100 mg or any of the acute medications listed above.
COVID-19 Pandemic-Related Vaccination Guidance
Given the ongoing COVID-19 pandemic, selected non-live vaccines (e.g., mRNA, non-replicating viral 
vector, protein subunit, etc.) to prevent SARS-CoV-2 infection may be administered during the study, as 
long as components of the vaccine are not contraindicated.
The decision to receive a locally available vaccine should be based on local guidance and an individual 
discussion between the treating physician and the subject.
The potential impact of atogepant and ubrogepant on SARS-CoV-2 vaccination is unknown. Therefore, 
study drug should be administered as follows:

The first dose of atogepant and ubrogepant, when possible, is preferred to be given at 
least ± 7 days from the SARS-CoV-2 vaccine administration.
Note:  The above guidance applies to all SARS-CoV-2 vaccine doses given as part of the complete 
vaccination course.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
These recommendations may be subject to change based on the evolving knowledge around the use of 
SARS-CoV-2 vaccines and as more data are collected in real-world scenarios and clinical trials.
Any SARS-CoV-2 vaccine information must be documented on the COVID-19 vaccine electronic case 
report form (eCRF).  Refer to the Operations Manual in Appendix F for instructions on reporting any AEs 
associated with the COVID-19 vaccine.
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including, 
but not limited to, the following:

Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the sponsor.

The investigator believes it is in the best interest of the subject.

The subject requests withdrawal from the study.

Eligibility criteria violation was noted after the subject started study drug and continuation of 
the study drug would place the subject at risk.

Introduction of prohibited medications or dosages and continuation of the study drug would 
place the subject at risk.

The subject becomes pregnant during the study.

The investigator determines the subject is significantly noncompliant with study procedures.

Subject meets one of the following criteria for ALT/AST elevations, and is advised not to be 
rechallenged:

ALT or AST ≥ 3 × ULN and the subject is symptomatic with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia 
(> 5%)

ALT or AST ≥ 3 × ULN and total bilirubin > 2 × ULN

ALT or AST ≥ 3 × ULN and international normalized ratio (INR) > 1.5

ALT or AST ≥ 5 × ULN for more than 2 weeks

ALT or AST ≥ 8 × ULN

Subjects who reply with "yes" to Questions 4 or 5 in the suicidal ideation section or "yes" to any 
question in the suicidal behavior section for the C-SSRS at Visits 2 through 9 must be withdrawn 
from the study and should receive appropriate follow-up as in routine clinical practice, including 
Early Termination Visit and Safety Follow-up (Visit 9).
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
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AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.
5.6 Follow-Up After Subject Discontinuation of Study Drug or from 
Study
If a subject early terminates study participation after taking at least one dose of study drug, the 
procedures outlined for the Early Termination Visit should be completed as soon as possible, preferably 
within 2 weeks.  In addition, the Safety Follow-up (Visit 9) should be completed 4 weeks after the Early 
Termination Visit to ensure all treatment-emergent AEs/serious adverse events (SAEs) have been 
resolved.
In the event a subject withdraws consent from the clinical study, PK and/or biomarker research will 
continue unless the subject explicitly requests analysis to be stopped.  When AbbVie is informed the 
subject has withdrawn and no longer wishes PK and/or biomarker samples research to continue, 
previous unanalyzed samples will not be analyzed and no new PK and/or biomarker analysis data will be 
collected for the withdrawn subject or added to the existing data or database(s).  A subject may 
withdraw consent for optional PK and/or biomarker research at any time and remain in the clinical 
study.  Data generated from the clinical study and/or optional PK and/or biomarker research, before the 
subject withdrawal of consent, will remain part of the study results.
5.7 Study Drugs
Atogepant tablets, manufactured by AbbVie, will be taken orally with or without food once daily 
beginning on Day 1 in the clinic and should be taken at approximately the same time each day.  If 
subjects should forget to take their atogepant dose at their regularly scheduled dosing time, they should 
take the forgotten dose as soon as they remember, and then take their next dose at the regularly 
scheduled dosing time. 
Ubrogepant tablets, manufactured by AbbVie, will be taken orally with or without food as needed to 
treat up to 8 breakthrough migraine headaches for the 4 weeks between each visit for Visits 5 to 8.
During this time, subjects will take a dose of ubrogepant 100 mg to treat their breakthrough migraine 
headache.  If after 2 hours the migraine attack has not resolved or the migraine headache returns within 
24 hours, subjects can choose either to take a second dose of ubrogepant 100 mg or any of the acute 
medications listed in Section 5.4.
All subject dosing will be recorded.  The study site personnel will document compliance.
AbbVie will provide atogepant tablets and ubrogepant tablets.  AbbVie-provided study drugs should not 
be substituted or alternately sourced, unless otherwise directed by AbbVie.
Atogepant tablets will be packaged in bottles with quantities sufficient to accommodate study design.  
Ubrogepant tablets will be packaged in blisters or packets with quantities sufficient to accommodate 
study design.  Each kit will be labeled per local requirements and this label must remain affixed to the 
kit.  Upon receipt, study drug should be stored as specified on the label and kept in a secure location at 
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the site.  Each kit will contain a unique kit number.  This kit number is assigned to a subject via the 
interactive response technology (IRT) and encodes the appropriate study drug to be dispensed at the 
subject's corresponding study visit.  Site staff will complete all blank spaces on the label before 
dispensing to subjects.  Study drug will only be used for the conduct of this study.
Upon completion of or discontinuation from study treatment, all original study drug units (containing 
unused study drugs) will be returned to the sponsor (or designee) or destroyed on site.  All return or 
destruction procedures will be according to instructions from the sponsor and according to local 
regulations following completion of drug accountability procedures.
Study drugs are described in Table 1.
Table 1.
Study Drugs
Study drug
Manufacturer
Mode of Administration
Dosage Form
Strength
Atogepant
AbbVie
Oral
Tablet
60 mg
Ubrogepant
AbbVie
Oral
Tablet
100 mg
5.8 Randomization/Drug Assignment
No randomization or stratification is required as this will be an open-label study.
All subjects will be assigned a unique identification number by the IRT at the Screening Visit.  For 
subjects who rescreen, the screening number assigned by the IRT at the initial Screening Visit should be 
used.
5.9 Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol except when necessary to 
eliminate an immediate hazard to study subjects.  The investigator is responsible for complying with all 
protocol requirements, written instructions, and applicable laws regarding protocol deviations.  If a 
protocol deviation occurs (or is identified), the investigator is responsible for notifying IEC/IRB, 
regulatory authorities (as applicable), and AbbVie.
5.10 Data Monitoring Committee and Hepatic Event Adjudication 
Committee
An external data monitoring committee (DMC) composed of clinicians and statisticians independent of 
AbbVie and with relevant expertise in their field will review data from the ongoing study.  The DMC is 
responsible for safeguarding the interests of trial subjects, assessing the safety of the interventions 
during the study, as well as for monitoring the integrity and interpretability of the study.  The DMC will 
provide recommendations to the sponsor regarding ongoing trial conduct or modifications to the trial as 
described in a separate DMC charter and identify any safety issues and trends.
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A separate DMC charter will be prepared outside of the protocol and will further describe the roles and 
responsibilities of the DMC members, frequency and scope of the data reviews, and expectations for 
blinded communications.
An external Hepatic Event Adjudication Committee (HEAC) will review and adjudicate events of post-
treatment elevations of ALT and/or AST ≥3 x ULN.  An Adjudication Charter will be established and will 
describe the standardized process for the adjudication of the events to determine whether the elevation 
was related to study drug(s).  The charter will describe the process for the adjudication of ALT and/or 
AST levels meeting the thresholds provided above, by the HEAC.  The purpose of the charter will be to 
provide a standardized process for the adjudication of data associated with these events in order to 
determine whether the elevation(s) are related to study drug.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product/device.  Complaints associated with any component of this study drug must 
be reported to AbbVie.
Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device damage or not 
working properly, or packaging issues.
Product complaints concerning the study drug and/or device must be reported to AbbVie within 24 
hours of the study site's knowledge of the event.
Reporting will be done via electronic data capture (EDC).  The date the product complaint details are 
entered into EDC and the form is saved represents the date reported to AbbVie.  A back-up paper form 
will be provided for reporting complaints related to unassigned product or in the event of an EDC system 
issue.  If a back-up paper form is used, the date the form is emailed to RD_PQC_QA@abbvie.com 
represents the date reported to AbbVie.
All follow-up information is to be reported to the sponsor (or an authorized representative) and 
documented in source as required by the sponsor.  Product complaints associated with AEs will be 
reported in the study summary.  All other complaints will be monitored on an ongoing basis.  Product 
complaints occurring during the study will be followed-up to a satisfactory conclusion.
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If an AE, whether associated with study drug or not, meets any of the following criteria, it is to be 
reported to AbbVie clinical pharmacovigilance as an SAE within 24 hours of the site being made aware of 
the SAE (refer to Section 4.2 of the Operations Manual for reporting details and contact information):
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the judgment of the investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken.  This does not include an event that would have been 
fatal if it had occurred in a more severe form.
Hospitalization or Prolongation 
of Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This does 
not include an emergency room visit or admission to an 
outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results 
in fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes 
with the activities of daily living of a study subject.  Disability is 
not intended to include experiences of relatively minor medical 
significance such as headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle).
Important Medical Event 
Requiring Medical or Surgical 
Intervention to Prevent Serious 
Outcome
An important medical event that may not be immediately life-
threatening or result in death or hospitalization but based on 
medical judgment may jeopardize the subject and may require 
medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life threatening, 
hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  
Additionally, any elective or spontaneous abortion or stillbirth is 
considered an important medical event.
All AEs reported from the time of study drug administration until 30 days or 5 half-lives, whichever is 
longer, after discontinuation of study drug administration will be collected, whether solicited or 
spontaneously reported by the subject.  In addition, study procedure-related serious and nonserious AEs 
will be collected from the time the subject signs the study-specific informed consent.
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk to subjects.
Adverse Events of Special Interest
All AEs of special interest must be reported within 24 hours of the time the investigator becomes aware 
of the event using the AE eCRF and the hepatic eCRF.
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The following AEs of special interest will be monitored during the study:

Treatment-emergent elevated ALT or AST laboratory value ≥3 × ULN.

Potential Hy's law cases: elevated ALT or AST laboratory value ≥3 × ULN and an elevated total 
bilirubin laboratory value ≥2 × ULN and, at the same time, an alkaline phosphatase laboratory
value < 2 × ULN.
Adverse Event Severity and Relationship to Study Drug
The investigators will rate the severity of each AE as mild, moderate, or severe.
The investigator will use the following definitions to rate the severity of each AE:
Mild
The AE is transient and easily tolerated by the subject.
Moderate
The AE causes the subject discomfort and interrupts the subject's 
usual activities.
Severe
The AE causes considerable interference with the subject's usual 
activities and may be incapacitating or life threatening.
The investigator will use the following definitions to assess the relationship of the AE to the use of study 
drug:
Reasonable Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship.
No Reasonable Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 24 hours after the site 
becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
discontinued (Section 5.5).  If a pregnancy occurs in a study subject or in the partner of a study subject, 
information regarding the pregnancy and the outcome will be collected.
In the event of pregnancy occurring in a subject's partner during the study, written informed consent 
from the partner must be obtained prior to collection of any such information.  AbbVie will provide a 
separate consent form for this purpose.  Pregnancy in a subject's partners will be collected from the 
date of the first dose through 30 days following the last dose of study drug.
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The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered an SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.
7 STATISTICAL METHODS and DETERMINATION OF SAMPLE 
SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol will be focused on primary and key secondary analyses.  
Complete and specific details of the statistical analysis will be described in the Statistical Analysis Plan 
(SAP).
7.2 Definition for Analysis Populations
The modified intent-to-treat 1 (mITT1) population includes all enrolled subjects who receive at least 
1 dose of study drug, have a baseline assessment, and have at least 1 postbaseline assessment during 
the open-label atogepant treatment period. The modified intent-to-treat 2 (mITT2) population includes 
all enrolled subjects who receive at least 1 dose of study drug, have a baseline assessment, and have at 
least 1 postbaseline assessment during the open-label atogepant+ubrogepant treatment period. The 
mITT1 or mITT2 populations will be used for efficacy analyses.
The safety population 1 consists of all subjects who received at least 1 dose of study drug during the 
open-label atogepant treatment period. The safety population 2 consists of all subjects who received at 
least 1 dose of study drug during the open-label atogepant + ubrogepant treatment period. The safety 
population 1 will be used for all baseline analysis, and the safety population 1 or safety population 2 will 
be used for safety analyses.
7.3 Handling Potential Intercurrent Events for the Primary and 
Exploratory Endpoints
The efficacy endpoints are exploratory in this study; therefore, no estimand attributes for efficacy 
endpoints will be provided.
7.4 Statistical Analyses for Efficacy
All analyses on the exploratory efficacy endpoints will be performed with the mITT1 or mITT2
population. 
Unless otherwise specified, change from baseline of continuous endpoints will be analyzed using a 
mixed-effect model for repeated measures (MMRM), including visit as a categorical fixed effect, and 
baseline value and baseline-by-visit interaction as covariates. An unstructured covariance matrix will be 
used to model the covariance of within-subject repeated measurements. The Kenward-Roger 
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approximation will be used to estimate the denominator degrees of freedom. The analysis will be 
performed based on all postbaseline values using only the observed cases without imputation of missing 
values. Nominal p-values and 95% confidence intervals (CIs) will be reported.
The MTOQ-6 score and percentages of migraine attacks treated with ubrogepant that result in pain 
freedom or pain relief will be summarized using descriptive statistics.
If the endpoints are binary or categorical, they will be summarized using descriptive statistics.
7.5 Statistical Analyses for Safety
The safety analyses will be performed using the safety population 1 or safety population 2. The safety 
endpoints include AEs, clinical laboratory evaluations, vital sign measurements, ECG parameters, the 
C-SSRS, and pregnancy test. For each of the clinical laboratory, vital sign, and ECG parameters, the last 
non-missing safety assessment before the first dose of study drug will be used as the baseline for all 
analyses of that safety parameter.
Continuous variables will be summarized by the number of subjects, mean, standard deviation (SD), 
median, minimum, and maximum values. Categorical variables will be summarized by number and 
percentage of subjects. The Kaplan-Meier Curve will provide the time to the occurrence of certain AEs,
if needed.
7.6 Interim Analysis
An interim analysis that includes all safety and efficacy analyses is planned when at least 30 subjects 
have completed Visit 8 to support access/reimbursement negotiations.
7.7 Overall Type I Error Control
No multiplicity adjustment for overall Type I Error Control is planned for this study.
7.8 Sample Size Determination
Approximately 235 subjects will be assigned to receive open-label atogepant 60 mg once daily for the 
preventive treatment of episodic migraine at Baseline/Visit 2 (Day 1). Based on historical data from 
previously completed clinical studies, it is assumed that 15% of subjects will discontinue from the study 
during the atogepant treatment period (Day 1 to Week 12). Therefore, approximately 200 subjects will 
be assigned to also receive ubrogepant 100 mg for the acute treatment of migraine starting at Visit 5
(Week 12). 
This sample size will provide estimation for AEs of interest occurring in either the open-label atogepant 
treatment period (Day 1 to Week 12) or the open-label atogepant and ubrogepant concomitant use 
treatment period (Weeks 12 to 24) with a precision (defined as the half width of 95% confidence 
interval) of approximately ± 3% to 5%.
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8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation (ICH) guidelines, applicable regulations, and guidelines governing clinical study 
conduct and the ethical principles that have their origin in the Declaration of Helsinki.  Responsibilities of 
the investigator are specified in Appendix B.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
11
START AND COMPLETION OF THE STUDY
The start-of-study is defined as the date of the first site activated.
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STUDY M23-072  |  Version 2.0
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The end-of-study is defined as the date of the last subject's last visit or date of the last follow-up 
contact, whichever is later.
12
REFERENCES
1.
Pellesi L, Do TP, Ashina H, et al. Dual Therapy With Anti-CGRP Monoclonal Antibodies and Botulinum 
Toxin for Migraine Prevention: Is There a Rationale? Headache. 2020;60(6):1056-65.
2.
D'Antona L, Matharu M. Identifying and managing refractory migraine: barriers and opportunities? J 
Headache Pain. 2019;20(1):89.
3.
Fischer MJ. The role of calcitonin gene-related peptide (CGRP) in the pathogenesis of primary 
headache. Drugs Fut. 2006;31(2):175-81.
4.
Atogepant Investigator's Brochure. Current Version.
5.
Ubrogepant Investigator's Brochure. Current Version.
6.
Qulipta USPI. 2021.
7.
Ubrelvy USPI. 2019.
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STUDY M23-072  |  Version 2.0
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX A. STUDY-SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AE
Adverse event
AESI 
Adverse events of special interest
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
CL/F
Apparent clearance
CBD
Cannabidiol 
CGRP
Calcitonin gene-related peptide 
COVID-19
Coronavirus Disease – 2019
CRP
C-reactive protein
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DMC 
Data Monitoring Committee 
eCRF
Electronic case report form
ECG
Electrocardiogram
EDC
Electronic data capture
EM
Episodic Migraine
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HEAC
Hepatic Event Adjudication Committee
HIT-6
Headache Impact Test-6
ICHD
International Classification of Headache Disorders
INR
International normalized ratio
IRT
Interactive response technology
IV
Intravenous
mITT 
Modified intent-to-treat
MSQ v2.1
Migraine-Specific Quality of Life Questionnaire version 2.1
MTOQ-6
Migraine Treatment Optimization Questionnaire-6
NSAID
Non-steroidal anti-inflammatory drug
PCR
Polymerase chain reaction
PGIC 
Patient Global Impression of Change 
PHQ-4
Patient Health Questionnaire-4
PK
Pharmacokinetic(s)
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QTcF
QT interval corrected for heart rate using Fridericia's formula
SAE
Serious adverse event
SAP
Statistical analysis plan
SNRI
Serotonin-norepinephrine reuptake Inhibitor
SSRI
Selective serotonin reuptake inhibitor
SUSAR
Suspected unexpected serious adverse reactions
THC
Tetrahydrocannabinol
ULN
Upper limit of normal
US
United States
V/F
Apparent volume of distribution
WPAI:MIGRAINE
Work Productivity and Activity Impairment Questionnaire: Migraine
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STUDY M23-072  |  Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M23-072:  A Phase 4, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of 
the Concomitant Use of Ubrogepant for the Acute Treatment of Migraine in Subjects Taking Atogepant for the 
Preventive Treatment of Episodic Migraine.
Protocol Date: 22 July 2022
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practices (GCP) and local laws and 
regulations and guidelines governing the study at the site location.  In signing the Investigator Agreement, the 
investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, current 
protocol and operations manual, and making changes to a protocol only after notifying AbbVie and the 
appropriate Institutional Review Board (IRB)/Independent Ethics Committee (IEC), except when necessary 
to protect the subject from immediate harm.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for investigational 
purposes and complying with the requirements relating to informed consent and ethics committees (e.g., 
IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the study drug(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about their 
obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records available 
for inspection by representatives of AbbVie and/or the appropriate regulatory agency, and retaining all 
study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial clinical 
protocol and all of its amendments.
9.
Reporting promptly, to AbbVie, the ethics committees/institutional review boards (as required) and other 
appropriate individuals (e.g., coordinating investigator, institution director): 

All changes in the research activity and all unanticipated problems involving risks to human subjects 
or others

Any departure from relevant clinical trial law or regulation, GCP, or the trial protocol that has the 
potential to affect the following:

Rights, safety, physical or mental integrity of the subjects in the clinical trial 

Scientific value of the clinical trial, reliability or robustness of data generated
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB review, 
and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
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STUDY M23-072  |  Version 2.0
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Program Lead
Clinical Study Leadership
Associate Director
Medical Writing
Therapeutic Area MD
Neuroscience Development
Senior Director and Therapeutic Area Head, 
Neuroscience
Statistics
Senior Manager
Statistics
Executive Director, Clinical Pharmacology
Clinical Pharmacology and 
Pharmacometrics
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STUDY M23-072  |  Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX E. PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
10 January 2022
Administrative Change 1
18 May 2022
The purpose of this version is to correct minor clerical errors for consistency throughout the protocol in 
addition to the following:

Incorporated changes from Protocol Administrative Change 1, including the name and contact 
information for the Therapeutical Area Medical Director and correction of typographical and 
formatting errors. 

Title page - added atogepant and ubrogepant to AbbVie Study Drug.

Updated the name and contact information of the Sponsor/Emergency Medical Contact 
globally.

Section 6.1 - referenced Section 4.2 of the Operations Manual for SAE reporting details and 
contact info to correct numerical typographical error.

Global - modified wording regarding use of ubrogepant for breakthrough migraine headaches 
and criteria for optional second dose of ubrogepant 100 mg or acute medications listed in 
Section 5.4, for clarity and consistency.

Synopsis and Section 4.1 - clarified which visits subjects should complete in the study.

Section 3.3 - modified language of exploratory efficacy endpoints for clarity and consistency.

Section 4.1 - modified language to clarify that subjects with exclusionary laboratory values at 
Visit 1 are not allowed to be rescreened, but clarified that total bilirubin > 1 × ULN in subjects 
with Gilbert's disease is not exclusionary.

Section 5.1 - modified eligibility Criterion 3 to clarify that to be eligible for the study, subjects 
must not have clinically significant laboratory values OR any of the specified ALT/AST, total 
bilirubin, or serum albumin criteria at Visit 1.

Section 5.1 - modified eligibility Criterion 8 to correct a typographical error and clarify that the 
number of headache days per month allowed for entry to the study is less than 15 headache 
days per month on average across the 3 months prior to Screening/Visit 1.

Section 5.1 and Section 5.2 - modified eligibility Criteria 34 and 35 and contraception 
requirements for males to align with safety profile of study drug.

Section 5.1 - modified eligibility Criterion 37 for clarity.

Section 5.3 - modified language of prohibited medications for clarity.

Section 5.3 - added reference to Section 5.4 for NSAID use for migraine and added/modified 
wording regarding restrictions of concomitant SSRIs and SNRIs.
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STUDY M23-072  |  Version 2.0
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
Section 5.5 - modified language regarding noncompliance to highlight determination of
investigator.

Section 5.5 - added language regarding which responses on C-SSRS require withdrawal from 
study and appropriate follow-up to minimize risk to subjects.

Section 5.6 - modified wording regarding follow-up after subject discontinuation of study drug 
or from study for clarity.

Section 5.7 - added wording regarding study drug return or destruction to align with sponsor 
instructions and local regulations.

Section 6.1 - modified wording to clarify that pregnancy in a subject's partners will be collected 
from the date of the first dose through 30 days following the last dose of study drug to be 
consistent with male contraception.

Section 7.2 and Section 7.4 - wording modified to clarify the definition of analysis populations 
and efficacy analyses.

Section 11 - renamed section to reflect that start-of-study definition was added.

Appendix A - added definitions for clarity.

Appendix B - modified language regarding responsibilities of the investigator to detail criteria 
that would meet prompt reporting.

Appendix C - updated the list of protocol signatories.

Appendix D - PROs formatted for consistency. 

Appendix E - added protocol summary of changes appendix.

Appendix F - Operations Manual modified to correct formatting errors and incorporate the 
following changes: 

Incorporated changes from Protocol Administrative Change 1 - added atogepant and 
ubrogepant to AbbVie Study Drug; update the name and contact information of the 
Sponsor/Emergency Medical Contact globally; and reformatted the PRO and 
Clinician-Reported Outcomes, Definition of Migraine Day subsection of the Operations 
Manual for clarity.

Global - Added/modified wording regarding use of ubrogepant for breakthrough migraine 
headaches for clarity and consistency.

Added PRO assessment MSQ v2.1 at Screening (Visit 1) for consistency with Appendix D of
the protocol, and added version of MSQ globally.

Clarified which visits subjects should complete if they take at least 1 dose of atogepant and 
discontinue.

Modified name of Subject Withdrawal section of the Operations Manual to reflect that 
section describes discontinuation of study drug or study participation.

Modified language of Methods and Timing of Safety Assessment section of the Operations 
Manual to clarify that after 30 days following the last dose of study drug or completion of 
study treatment only spontaneously reported SAEs will be collected.
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STUDY M23-072  |  Version 2.0
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
Added wording regarding RAVE system to the Reporting AEs and Intercurrent Illnesses 
section of the Operations Manual for clarity.

Global - Added/modified wording regarding use of ubrogepant for breakthrough migraine 
headaches for clarity and consistency.

Added additional medications as examples of prohibited medications to minimize risk to 
subjects.

Modified the list of migraine-preventive medications with proven efficacy for clarity; 
specified flunarizine is not available in the United States, added verapamil as an example of 
a calcium channel blocker, and added a reference source.

Added a reference section for the Operations Manual.
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SAP_001.pdf: 
Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
1 
Statistical Analysis Plan for Study M23-072
A Phase 4, Multicenter, Open-Label Study to 
Evaluate the Safety, Tolerability, and Efficacy of the 
Concomitant Use of Ubrogepant for the Acute 
Treatment of Migraine in Subjects Taking Atogepant 
for the Preventive Treatment of Episodic Migraine
Date:  07 December 2022
Version 2.0
NCT05264129


Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
2 
Table of Contents
1.0
Introduction .............................................................................5
2.0
Study Design and Objectives..................................................5
2.1
Objectives, Hypotheses and Estimands ..................................................... 5
2.2
Study Design Overview ............................................................................. 6
2.3
Treatment Assignment and Blinding ......................................................... 8
2.4
Sample Size Determination ........................................................................ 9
3.0
Endpoints..................................................................................9
3.1
Primary Endpoint ....................................................................................... 9
3.2
Exploratory Efficacy Endpoint(s) .............................................................. 9
3.3
Safety Endpoint(s) ................................................................................... 11
4.0
Analysis Populations .............................................................11
5.0
Subject Disposition................................................................12
6.0
Study Treatment Duration and Compliance ......................13
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications ....................14
7.1
Demographics and Baseline Characteristics ............................................ 14
7.2
Medical History ....................................................................................... 14
7.3
Prior and Concomitant Medications ........................................................ 15
8.0
Handling of Potential Intercurrent Events for the 
Primary and Secondary Endpoints......................................15
9.0
Efficacy Analyses...................................................................16
9.1
General Considerations ............................................................................ 16
9.2
Handling of Missing Data ........................................................................ 16
9.3
Exploratory Efficacy Endpoint(s) and Analyses ...................................... 16
9.3.1
Exploratory Efficacy Endpoint(s) ............................................................ 16
9.3.2
Analysis of Exploratory Efficacy Endpoints ........................................... 16
9.4
Efficacy Subgroup Analyses .................................................................... 18
10.0
Safety Analyses ......................................................................19
10.1
General Considerations ............................................................................ 19
10.2
Adverse Events ........................................................................................ 19
10.2.1
Treatment-Emergent Adverse Events ...................................................... 20


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10.2.2
Adverse Event Overview ......................................................................... 20
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT ....................... 21
10.2.4
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ............................................................................... 21
10.2.5
Adverse Events of Special Interest .......................................................... 21
10.3
Laboratory Data ....................................................................................... 22
10.4
Vital Signs ................................................................................................ 24
10.5
Other Safety Analyses .............................................................................. 24
10.5.1
Electrocardiogram .................................................................................... 24
10.5.2
Columbia-Suicide Severity Rating Scale ................................................. 25
10.6
Safety Subgroup Analyses ....................................................................... 26
11.0
Interim Analyses....................................................................26
11.1
Data Monitoring Committee .................................................................... 27
12.0
Overall Type-I Error Control ..............................................27
13.0
COVID-19 Related Analyses ................................................27
14.0
Version History......................................................................28
15.0
References...............................................................................30
List of Tables
Table 1.
SAP Version History Summary ............................................................... 28
Table 2.
Item Values for MSQ Item Responses ..................................................... 31
Table 3.
Item Values for HIT-6 Item Responses ................................................... 33
Table 4.
Potentially Clinically Significant Criteria for Clinical Laboratory 
Parameters ................................................................................................ 36
Table 5.
Criteria for Hepatic Laboratory Abnormalities ........................................ 37
Table 6.
Potentially Clinically Significant Criteria for Vital Signs 
Parameters ................................................................................................ 39
Table 7.
Potentially Clinically Significant Criteria for ECG Parameters .............. 40
Table 8.
ECG Post-baseline Values of Clinical Interest ........................................ 40
Table 9.
List of Selected Parameters Reported in Conventional Unit ................... 41
Table 10.
Presenting Laboratory Data Using SI and Conventional Units in 
Narratives ................................................................................................. 42


Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
4 
List of Figures
Figure 1.
Study Schematic ......................................................................................... 8
List of Appendices
Appendix A.
Derivation of Efficacy Variables ............................................................. 31
Appendix B.
Protocol Deviations .................................................................................. 35
Appendix C.
Potentially Clinically Significant Criteria for Safety ............................... 36
Appendix D.
Laboratory Parameters in Conventional Unit .......................................... 41
Appendix E.
List of Abbreviations ............................................................................... 43
Appendix F.
Changes to Protocol-planned Analyses ................................................... 44


Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
5 
1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for atogepant Study 
M23-072, A Phase 4, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, 
and Efficacy of the Concomitant Use of Ubrogepant for the Acute Treatment of Migraine 
in Subjects Taking Atogepant for the Preventive Treatment of Episodic Migraine. 
Study M23-072 is to evaluate the safety and tolerability of the concomitant use of 
ubrogepant 100 mg for the acute treatment of breakthrough migraine headache in subjects 
taking atogepant 60 mg once daily for preventive treatment of EM. 
The SAP will not be updated in case of administrative changes or amendments to the 
protocol unless the changes impact the analysis. 
Unless noted otherwise, all analyses will be performed using SAS Version 9.4 (SAS 
Institute Inc., Cary, NC 27513) or later under the LINUX operating system. 
2.0
Study Design and Objectives
2.1
Objectives, Hypotheses and Estimands
The primary objective of this study is to evaluate the safety and tolerability of the 
concomitant use of ubrogepant 100 mg for the acute treatment of breakthrough migraine 
headache in subjects taking atogepant 60 mg once daily for preventive treatment of EM. 
The exploratory objectives are:
●
To evaluate the clinical benefit of the concomitant use of ubrogepant 100 mg, 
taken as needed, and atogepant 60 mg once daily in subjects with EM. 
●
To explore the efficacy of ubrogepant 100 mg, taken as needed, for the acute 
treatment of migraine in subjects taking atogepant 60 mg once daily for 
preventive treatment of EM.


Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
6 
The efficacy endpoints are exploratory in this study; therefore, no estimand attributes for 
efficacy endpoints will be provided. 
2.2
Study Design Overview
This is a multicenter, open-label, Phase 4 study conducted in the United States (US) to 
evaluate the safety, tolerability, and efficacy of the concomitant use of ubrogepant 100 mg 
for the acute treatment of breakthrough migraine headache in subjects taking atogepant 60 
mg once daily for preventive treatment of EM.
Subject participation will begin with up to a 1-week screening period. Subjects who 
continue to meet all entry criteria at baseline/Visit 2 (Day 1) will be assigned atogepant 
60 mg once daily for the preventive treatment of migraine. 
Screen failures are defined as subjects who consent to participate in the study, however, 
are not subsequently assigned to receive study drug. Rescreening of screen failures is 
permitted in certain situations, with permission from the Sponsor, however, subjects with 
clinically laboratory values at Visit 1 (including ALT or AST > 1 x ULN, total bilirubin 
> 1 or serum albumin < 2.8 g/dL) are not allowed to be rescreened. 
The open-label atogepant treatment period will last for 12 weeks (Visits 2-5). During this 
study period, subjects will use their usual medications for the acute treatment of 
breakthrough migraine headaches. At Visit 5, subjects who complete the open-label 
atogepant treatment period will continue into the open-label atogepant + ubrogepant 
concomitant use period which will last for an additional 12 weeks (Visits 5 to 8). During 
this study period, subjects will continue to take atogepant 60 mg once daily and will also 
be provided ubrogepant 100 mg to treat up to 8 breakthrough migraine headaches of any 
pain intensity per 4-week visit interval. For each breakthrough migraine, subjects will take 
a dose of ubrogepant 100 mg to treat their breakthrough migraine headache. If the 
migraine headache pain persists or returns, subjects may opt to take the second dose of 
ubrogepant 100 mg or their own medication starting 2 to 24 hours after the first dose of 
ubrogepant 100 mg was taken. 


Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
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There will be a total of 9 scheduled clinic visits:  Screening/Visit 1 (Week -1), 
Baseline/Visit 2 (Day 1), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 
(Week 16), Visit 7 (Week 20), Visit 8/Early Termination (Week 24), and Visit 9/Safety 
Follow-up (Week 28). The total duration of study participation is 29 weeks. Total 
treatment duration is 24 weeks.  
All subjects who take at least 1 dose of atogepant 60 mg will enter a safety follow-up 
period of 4 additional weeks after their last dose of study drug. All subjects, regardless of 
the number of doses of study drug which are self-administered, should complete Visits 8 
and 9, unless the subject has withdrawn consent. An interim analysis that includes all 
safety and efficacy analyses is planned. Details are provided in Section 10.6. 
The schematic of the study is shown in Figure 1. 


Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
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Figure 1. 
Study Schematic
2.3
Treatment Assignment and Blinding
Approximately 235 subjects will be enrolled to receive the following open-label 
treatment: 
●
Open-label atogepant treatment period:  atogepant 60 mg once daily for 
12 weeks (Day 1 to Week 12) 
●
Open-label atogepant and ubrogepant concomitant use treatment period: 
atogepant 60 mg once daily + ubrogepant 100 mg as needed to treat 
breakthrough migraine headache for 12 weeks (Week 12 to 24) 


Atogepant (AGN-241689)
M23-072 – Statistical Analysis Plan
Version 2.0 – 07 December 2022
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No randomization or stratification is required as this will be an open-label study. 
All subjects will be assigned a unique identification number by the IRT at the Screening 
Visit. For subjects who rescreen, the screening number assigned by the IRT at the initial 
Screening Visit should be used. 
2.4
Sample Size Determination
Approximately 235 subjects will be assigned to receive open-label atogepant 60 mg once 
daily for the preventive treatment of episodic migraine at Baseline/Visit 2 (Day 1). Based 
on historical data from previously completed clinical studies, it is assumed that 15% of 
subjects will discontinue from the study during the atogepant treatment period (Day 1 to 
Week 12). Therefore, approximately 200 subjects will be assigned to also receive 
ubrogepant 100 mg for the acute treatment of migraine starting at Visit 5 (Week 12). 
This sample size will provide estimation for AEs of interest occurring in either the open-
label atogepant treatment period (Day 1 to Week 12) or the open-label atogepant and 
ubrogepant concomitant use treatment period (Weeks 12 to 24) with a precision (defined 
as the half width of 95% confidence interval) of approximately ± 3% to 5%. 
3.0
Endpoints
3.1
Primary Endpoint
The primary endpoint is to assess the safety endpoints, including adverse event (AE) 
monitoring, vital sign measurements, electrocardiogram (ECG) variables, clinical 
laboratory testing (hematology, chemistry, and urinalysis), and Columbia Suicide Severity 
Rating Scale (C-SSRS).
3.2
Exploratory Efficacy Endpoint(s)
●
Change from baseline in mean monthly migraine days, headache days, and 
acute medication use days across Weeks 1 to 12, Weeks 13 to 24, and at each 
4-week interval.


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●
Achievement of at least ≥ 25%, ≥ 50%, ≥ 75%, and 100% reduction in mean 
monthly migraine days across Weeks 1 to 12, Weeks 13 to 24, and at each 4-
week interval. 
●
Percentages of migraine attacks treated with ubrogepant that result in pain 
freedom at 2 hours, pain relief at 2 hours, sustained pain freedom from 2 to 
24 hours, and sustained pain relief from 2 to 24 hours across Weeks 13 to 24, 
and at each 4-week interval. 
●
Patient satisfaction with atogepant at Week 12 and Week 24. 
●
Patient satisfaction with ubrogepant, taken as needed, at Week 24. 
●
Patient satisfaction with the concomitant use of atogepant and ubrogepant 
(taken as needed) at Week 24.
●
Change from baseline in the Headache Impact Test (HIT)-6 total score at 
Weeks 4, 8, 12, 16, 20, and 24. 
●
At least a 5-point improvement (decrease) from baseline in HIT-6 total score at 
Weeks 4, 8, 12, 16, 20, and 24. 
●
Patient Global Impression of Change (PGIC) of "much better" or "very much 
better" at Week 12 (atogepant) and Week 24 (atogepant + ubrogepant). 
●
Change from baseline in percent work time missed, percent impairment while 
working, percent overall impairment, and percent activity impairment due to 
migraine at Weeks 4, 8, 12, 16, 20, and 24 as assessed by the Work 
Productivity and Activity Impairment Questionnaire: Migraine 
(WPAI:MIGRAINE).
●
Change from baseline in the Migraine-Specific Quality-of-Life Questionnaire 
(MSQ) v2.1 Role Function-Preventive domain score at Weeks 4, 8, 12, 16, 20, 
and 24. 
●
Change from baseline in the MSQ v2.1 Role Function-Restrictive domain 
score at Weeks 4, 8, 12, 16, 20, and 24. 
●
Change from baseline in the MSQ v2.1 Emotional Function domain score at 
Weeks 4, 8, 12, 16, 20, and 24. 
●
Change from baseline in the Patient Health Questionnaire (PHQ)-4 score at 
Weeks 4, 8, 12, 16, 20, and 24. 


Atogepant (AGN-241689)
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●
Migraine Treatment Optimization Questionnaire (MTOQ)-6 score at Weeks 
16, 20, and 24. 
3.3
Safety Endpoint(s)
The safety parameters include including adverse event (AE) monitoring, vital sign 
measurements, electrocardiogram (ECG) variables, clinical laboratory testing 
(hematology, chemistry, and urinalysis), and Columbia Suicide Severity Rating Scale 
(C-SSRS). For clinical laboratory, vital sign, and ECG parameters, the last non-missing 
safety assessment before the first dose of treatment will be used as the baseline for all 
analyses of that safety parameter.
All AEs and other safety data will be presented in the listings at the subject level.
4.0
Analysis Populations
The modified intent-to-treat 1 (mITT1) population includes all enrolled subjects who 
received at least 1 dose of study drug, have a baseline assessment, and have at least 
1 postbaseline assessment during the open-label atogepant treatment period. The modified 
intent-to-treat 2 (mITT2) population includes all enrolled subjects who received at least 1 
dose of study drug, have a baseline assessment, and have at least 1 postbaseline 
assessment during the open-label atogepant + ubrogepant treatment period. The mITT1 or 
mITT2 populations will be used for all efficacy analyses.
The Safety Population 1 consists of all subjects who received at least 1 dose of study drug 
during the open-label atogepant treatment period. The Safety Population 2 consists of all 
subjects who received at least 1 dose of study drug during the open-label atogepant + 
ubrogepant treatment period. The Safety Population 1 or Safety Population 2 will be used 
for safety analyses.


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5.0
Subject Disposition
Summaries will be provided for subjects in each of the following categories: 
●
Subjects who were screened;
●
Subjects enrolled in the study; 
●
Subjects who completed the study (or did not with associated reasons); 
●
Subjects who discontinued the study drug, including atogepant and 
ubrogepant; 
●
Subjects who took at least one dose of study drug during the open-label 
atogepant treatment period (Safety Population 1); 
●
Subjects who completed open-label atogepant treatment period;
●
Subjects who took at least one dose of study drug, either atogepant or 
ubrogepant, during the open-label atogepant + ubrogepant treatment period 
(Safety Population 2); 
●
Subjects who completed open-label atogepant + ubrogepant treatment period; 
●
Subjects who prematurely discontinued the open-label atogepant treatment 
period (including reasons for premature discontinuation); 
●
Subjects who prematurely discontinued the open-label atogepant + ubrogepant 
treatment period (including reasons for premature discontinuation); 
●
Subjects who prematurely discontinued the study (including reasons for 
premature discontinuation); 
●
Subjects in the mITT 1 Population; 
●
Subjects in the mITT 2 Population. 
Screen failure subjects (i.e., subjects who consented to participate in the study but were 
not enrolled) and the associated reasons for failure to enroll will be summarized and listed 
for all screened subjects.
The summary of subject accountability by investigator also will include the number of 
subjects who enrolled in the study, completed the study, discontinued study drug, and 


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subjects in the mITT 1, mITT 2, Safety Population 1, and Safety Population 2, 
respectively.  
6.0 
Study Treatment Duration and Compliance
Duration of treatment for atogepant, defined for each subject as last dose date minus first 
dose date + 1, will be summarized for the Safety Population 1 and Safety Population 2. 
Duration of treatment for atogepant will be summarized for each period (open-label 
atogepant period or open-label atogepant + ubrogepant period) and the entire open-label 
period using the number of subjects treated, mean, standard deviation, median, minimum 
and maximum. In addition, the number and percentage of subjects in each treatment 
duration of ≥ 1 day, ≥ 7 days, ≥ 14 days, ≥ 21 days, ≥ 28 days, ≥ 35 days, ≥ 42 days, ≥ 49 
days, ≥ 56 days, ≥63 days, ≥ 70 days, ≥ 77 days, ≥ 84 days, ≥ 91 days, ≥ 98 days, ≥ 105 
days, ≥ 112 days, ≥ 119 days, ≥ 126 days, ≥ 133 days, ≥ 140 days, ≥ 147 days, ≥ 154 
days, ≥ 161 days, ≥ 168 days will be summarized. 
Duration of treatment for ubrogepant, defined as the number of doses and days of 
ubrogepant taken, will be summarized for the Safety Population 2, by the number of 
subjects treated, mean, standard deviation, median, minimum and maximum. 
Treatment compliance of atogepant for a specific period (open-label atogepant period and 
open-label atogepant + ubrogepant period) is defined as the number of atogepant doses 
actually taken by a subject during that period divided by the number of atogepant doses 
that were expected to be taken during the same period multiplied by 100. Percent 
treatment compliance will be summarized in each period for the Safety Population 1 and 
Safety Population 2. 
Ubrogepant is taken as needed, so no treatment compliance will be provided for 
ubrogepant.  


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7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications
7.1
Demographics and Baseline Characteristics
Demographics and baseline characteristics will be summarized for the Safety Population 1 
and 2. Continuous demographic variables include age, weight, height, and body mass 
index (BMI). Categorical demographic variables include sex, ethnicity (Hispanic or 
Latino, Not Hispanic or Latino), race, race group (White, All Other Races), BMI group 
(< 25, 25-30, and ≥ 30), and age group (< 20, 20-29, 30-39, 40-49, 50-59, 60-69, and 
≥ 70). 
Disease characteristics are contained in migraine history, including diagnosis, duration of 
disorder, migraine prevention medication in the past, average number of migraine and
headache days per month at baseline and in the last 3 months, and acute medications taken 
to treat migraine headaches. 
Categorical variables will be summarized with the number and percentage of subjects; 
percentage will be calculated based on the non-missing observations. Continuous 
variables will be summarized with descriptive statistics (number of non-missing 
observations, mean and standard deviation, median, Q1, Q3, minimum, and maximum). 
7.2
Medical History
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). The actual version of the MedDRA coding dictionary will be noted in the 
statistical tables and clinical study report. The number and percentage of subjects in each 
medical history category (by MedDRA system organ class and preferred term) will be 
summarized. The system organ class (SOC) will be presented in alphabetical order, and 
the preferred terms will be presented in alphabetical order within each SOC. Subjects 
reporting more than one condition/diagnosis will be counted only once in each row (SOC 
or preferred term). Migraine history will be summarized separately according to eCRF. 


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7.3
Prior and Concomitant Medications
Prior and concomitant medications will be summarized separately by generic name. The 
number and percentage of subjects taking prior and concomitant medications will be 
summarized by generic name. Concomitant medication will be summarized for each 
open-label period and overall. A prior medication is defined as any medication taken prior 
to the date of the first dose of study drug.  
A concomitant medication in the open-label atogepant treatment period (Period 1) is 
defined as any medication that started prior to the date of the first dose of study drug and 
continue to be taken after the first dose of study drug or any medication that started on or 
after the date of the first dose of study drug, but not after the date of the last dose of study 
drug in Period 1 plus 30 days (if subject discontinued from study drug in Period 1) or 
Visit 5 whichever comes later.  
A concomitant medication in the open-label atogepant + ubrogepant treatment period 
(Period 2) is defined as any medication that started prior to the date of the first dose of 
study drug in Period 2 and continue to be taken after the first dose of study drug in Period 
2 or any medication that started on or after the date of the first dose of study drug in 
Period 2, but not after the date of the last dose of study drug plus 30 days or Visit 9 
whichever comes later.  
The number and percentage of subjects taking medications will be summarized by generic 
drug name based on the World Health Organization (WHO) Drug Dictionary Enhanced 
for both prior and concomitant medications.  
8.0
Handling of Potential Intercurrent Events for the 
Primary and Secondary Endpoints
The efficacy endpoints are exploratory, so no handling of intercurrent events for efficacy 
endpoints will be provided.  


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9.0
Efficacy Analyses
9.1
General Considerations
All efficacy analyses will be conducted in the mITT 1 or mITT 2 Population.  
9.2
Handling of Missing Data
Descriptive statistics for efficacy endpoints will be based on observed cases (OC) only. 
Missing data will be handled using mixed model for repeated measures (MMRM) without 
imputation for the efficacy analysis for continuous endpoints unless specified otherwise.  
9.3
Exploratory Efficacy Endpoint(s) and Analyses
9.3.1
Exploratory Efficacy Endpoint(s)
The exploratory efficacy endpoints are listed in Section 3.2.  
9.3.2
Analysis of Exploratory Efficacy Endpoints
Continuous Endpoints 
The change from baseline in mean monthly migraine days, headache days, and acute 
medication use days across Weeks 1 to 12, Weeks 13 to 24, and at each 4-week interval
will be analyzed using a mixed-effect model for repeated measures (MMRM) for each 
period (open-label atogepant period or open-label atogepant + ubrogepant period), 
including visit as a categorical fixed effect, and baseline value and baseline-by-visit 
interaction as covariates. An unstructured covariance matrix will be used to model the 
covariance of within-subject repeated measurements. The Kenward-Roger approximation 
will be used to estimate the denominator degrees of freedom. The analysis will be 
performed based on postbaseline values using only the observed cases without imputation 
of missing values. Contrasts will be constructed to obtain the average treatment effects 
across the 12-week period for Weeks 1 to 12 or Weeks 13 to 24. The treatment effect 
(across the 12-week period for Weeks 1 to 12 or Weeks 13 to 24, and at each 4-week 


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interval) will be estimated by the least square (LS) Means, the standard error (SE) and 
95% confidence intervals.  
(HIT)-6 total score is derived as specified in the Appendix A. The change from baseline 
for (HIT)-6 total score will be analyzed similarly as above using MMRM.
The percent work time missed, percent impairment while working, percent overall 
impairment, and percent activity impairment due to migraine at Weeks 4, 8, 12, 16, 20, 
and 24 as assessed by the Work Productivity and Activity Impairment Questionnaire: 
Migraine (WPAI:MIGRAINE) are derived as specified in Appendix A. The change from 
baseline for these endpoints will be analyzed similarly as above using MMRM.
MSQ Role Function-Preventive domain score, Role Function-Restrictive domain score 
and Emotional Function domain score are derived as specified in Appendix A. The 
change from baseline for these endpoints will be analyzed similarly as above using 
MMRM.
(PHQ)-4 score is derived as specified in Appendix A. The change from baseline for 
(PHQ)-4 will be analyzed similarly as above using MMRM.
The MTOQ-6 score is derived as specified in Appendix A. The MTOQ-6 score will be 
summarized by visit.  
Percentages of migraine attacks treated with ubrogepant that result in pain freedom at 2 
hours, pain relief at 2 hours, sustained pain freedom from 2 to 24 hours, and sustained 
pain relief from 2 to 24 hours across Weeks 13 to 24 and at each 4-week interval will be 
summarized using descriptive statistics.  
Binary or Categorical Endpoints 
The responders are defined as subjects with at least 25%, 50%, 75%, and 100% reduction 
compared to baseline in mean monthly migraine days across Weeks 1 to 12, Weeks 13 to 
24, and at each 4-week interval. They will be summarized using descriptive statistics.


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Patient satisfaction with atogepant, ubrogepant, and concomitant use of atogepant and 
ubrogepant are categorized as extremely satisfied, satisfied, slightly satisfied, neither 
satisfied nor dissatisfied, slightly dissatisfied, dissatisfied, and extremely dissatisfied. The 
proportions of patient satisfaction responders, defined as subjects who are satisfied or 
extremely satisfied with the study treatment for migraine prevention, will be summarized 
using descriptive statistics by visits.
Proportions of subjects with at least a 5-point improvement (decrease) from baseline in 
HIT-6 total score at Weeks 4, 8, 12, 16, 20, and 24 will be summarized using descriptive 
statistics. 
Proportions of subjects with PGIC of "much better" or "very much better" at Week 12 
(atogepant) and Week 24 (atogepant + ubrogepant) will be summarized. 
9.4
Efficacy Subgroup Analyses
For the efficacy endpoint, change from baseline in mean monthly migraine days, 
headache days, and acute medication use days, subgroup analyses will be performed by 
ubrogepant usage subgroups.  
Two subgroups will be applied in subgroup analyses for subjects who took ubrogepant: 
Subgroups by number of ubrogepant use days:
●
Never used ubrogepant 
●
Low ubrogepant use:  1-3 days of ubrogepant taken in the atogepant + 
ubrogepant treatment period 
●
Moderate ubrogepant use:  4-9 days of ubrogepant taken in the atogepant + 
ubrogepant treatment period
●
High ubrogepant use: >=10 days of ubrogepant taken in the atogepant + 
ubrogepant treatment period


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Subgroup by number of ubrogepant doses taken: 
●
Never used ubrogepant 
●
Low ubrogepant use: 1-6 doses of ubrogepant taken in the atogepant + 
ubrogepant treatment period 
●
Moderate ubrogepant use: 7-18 doses of ubrogepant taken in the atogepant + 
ubrogepant treatment period 
●
High ubrogepant use: 19+ doses of ubrogepant taken in the atogepant + 
ubrogepant treatment period 
For each subgroup analysis, summary statistics will be provided, including mean and 
standard deviation, minimum, maximum, and 95% CI for baseline and change from 
baseline across Weeks 13-24.  
10.0
Safety Analyses
10.1
General Considerations
The safety analyses will be performed using the Safety Population 1 or 2. The safety 
endpoints include AEs, clinical laboratory evaluations, vital sign measurements, ECG 
parameters, the C-SSRS, and pregnancy test. For each of the clinical laboratory, vital sign, 
and ECG parameters, the last non-missing safety assessment before the first dose of study 
drug will be used as the baseline for all analyses of that safety parameter.  
Continuous variables will be summarized by the number of subjects, mean, standard 
deviation (SD), median, Q1, Q3, minimum, and maximum values. Categorical variables 
will be summarized by number and percentage of subjects.  
10.2
Adverse Events
Adverse events (AEs) will be summarized and presented using primary MedDRA System 
Organ Class (SOCs) and preferred terms (PTs) according to the version of MedDRA 
coding dictionary used for the study at the time of database lock. The actual version of the 
MedDRA coding dictionary used will be noted in the AE tables and in the clinical study 


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report. Specific adverse events will be counted once for each subject for calculating 
percentages, unless stated otherwise. In addition, if the same adverse event occurs 
multiple times within a subject, the highest severity and level of relationship to 
investigational products will be reported. 
10.2.1
Treatment-Emergent Adverse Events
Treatment-emergent AEs are defined as any AE with the onset that is after the first dose 
of study drug. Events when the onset date is the same as the study drug start date are 
assumed to be treatment-emergent. An AE that occurs more than 30 days after the last 
dose of open-label study treatment or Visit 8 whichever comes later will not be counted as 
a TEAE.  
The number and percentage of subjects experiencing treatment-emergent AEs will be 
summarized by the open-label atogepant treatment period, the open-label concomitant 
atogepant + ubrogepant treatment period, and the entire treatment period. 
TEAEs that started after the date of last dose of study treatment will be considered as 
newly emergent. The number and percentage of subjects reporting newly emergent 
TEAEs will be summarized by system organ class and preferred term. 
10.2.2
Adverse Event Overview
An overall of AEs will be presented consisting of the number and percentage of subjects 
experiencing at least one event for each of the following AE categories:
●
Any treatment-emergent AE
●
Any treatment-emergent AE related to study drugs (atogepant and ubrogepant) 
according to the investigator 
●
Any severe treatment-emergent AE
●
Any serious treatment-emergent AE
●
Any treatment-emergent AE leading to discontinuation of study drugs 
(atogepant and ubrogepant) 


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●
Any treatment-emergent AE leading to death
●
All deaths
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
Treatment-emergent adverse events will be summarized, for each treatment period and 
overall, by SOC and PT; by maximum relationship to study drug as assessed by the 
investigator (e.g., reasonable possibility or no reasonable possibility) and SOC and PT; by 
maximum severity and SOC and PT. Specific adverse events will be counted once for 
each subject for calculating percentages, unless stated otherwise. In addition, if the same 
adverse event occurs multiple times within a subject, the highest severity and level of 
relationship to investigational product will be reported. 
The incidence of common (≥ 2% and ≥ 5% [after rounding] of subjects) TEAEs will be 
summarized by preferred term for each treatment period and overall.  
Kaplan-Meier Curves will be provided for the time to the occurrence of certain AEs 
(nausea, constipation, fatigue/somnolence, decrease appetite) for the entire open-label 
treatment period.  
10.2.4
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
The number and percentage of subjects in the Safety Population 1 and Safety Population 2 
who have SAEs (including deaths) and AEs leading to study drug discontinuation will be 
summarized by SOC and PT. 
In addition, the list for SAEs (including deaths) and AEs leading to study intervention 
discontinuation will provided. 
10.2.5
Adverse Events of Special Interest
All AEs of special interest must be reported within 24 hours of the time the investigator 
becomes aware of the event using the AE eCRF and the hepatic eCRF.


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The following AEs of special interest will be monitored during the study: 
●
Treatment-emergent elevated ALT or AST laboratory value ≥ 3 × ULN.
●
Potential Hy's law cases:  elevated ALT or AST laboratory value ≥ 3 × ULN 
and an elevated total bilirubin laboratory value ≥ 2 × ULN and, at the same 
time, an alkaline phosphatase laboratory value < 2 × ULN.
10.3
Laboratory Data
Data collected from central laboratories, including additional laboratory testing due to an 
SAE, will be used in all analyses, except for Baseline where SAE-related laboratory 
assessments on or before the first dose of study drug without timestamp will be excluded. 
The details for SAE-related laboratory baseline can be found in the SPP. The clinical 
laboratory tests defined in the protocol (e.g., hematology, clinical chemistry and 
urinalysis) will be summarized.
Each laboratory variable will be summarized for all time points (starting with Baseline) 
with the number of non-missing observations, mean and standard deviation, median, Q1, 
Q3, minimum and maximum. Mean change from baseline to each applicable post-baseline 
visit will be summarized with the number of observations, baseline mean, and visit mean. 
The change from baseline mean, standard deviation, median, Q1, Q3, minimum and 
maximum will be presented for the mean change from baseline. In addition, descriptive 
statistics for values and changes from the baseline values in conventional units at each 
assessment time point will be presented for selected clinical laboratory parameters listed 
in Appendix D. A description of reporting the lab values in conventional units in patient 
narratives (along with the standard reporting in SI units) is presented at the end of 
Appendix D. 
Changes in laboratory parameters will be summarized using shift tables categorized as 
low, normal, or high based on the normal ranges of the laboratory used for each sample. A 
shift table will be provided to summarize shifts from baseline to the final post-baseline 
value for all lab categories. 


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Laboratory abnormalities will be evaluated based on potentially clinically significant 
(PCS) criteria (Table 4). For each laboratory PCS criterion, the number and percentage of 
subjects who have a laboratory value meeting the criteria will be summarized in Safety 
Populations 1 and 2 for each treatment period and overall. Listings will be provided to 
summarize subject-level laboratory data for subjects meeting PCS criteria.
The number and percentage of subjects meeting each of the criteria for postbaseline 
hepatic laboratory abnormalities listed in Table 5 will be summarized. The percentages 
will be calculated relative to the number of subjects with at least 1 available postbaseline 
assessment. The numerator will be the total number of subjects having at least 1 
postbaseline value that meets the specific category during the study. A supportive listing 
will also be provided. 
The number and percentage of subjects with an adjudicated case (i.e., ALT ≥ 3 x ULN 
and/or AST ≥ 3 x ULN) will be summarized by relationship of ALT or AST elevation to 
study medication. The percentages will be calculated relative to the number of subjects 
with at least 1 adjudicated case. The numerator will be the number of subjects with at least 
1 adjudicated case in the specific category of relationship. If a subject has more than 1 
adjudicated case, he or she will be counted in the most relevant category of relationship. 
Subjects with an adjudicated case (i.e., ALT ≥ 3 x ULN or AST ≥ 3 x ULN) will be listed 
with their ALT and AST assessments, adjudication dates, relationship of ALT or AST 
elevation to study medication, and confounding factor(s). Additional listings will be 
provided for subjects who meet ALT ≥ 3 x ULN or AST ≥ 3 x ULN and/or potential Hy's 
law and have one of the following categories: at least 1 abnormal liver biochemistry risk 
factor, at least 1 liver disease sign and symptom, at least 1 liver diagnostic test performed, 
consultation with a specialist for liver evaluation, liver lab tests performed, and drug 
screen performed, respectively. 
Potential Hy's Law criteria within a 24-hour window is defined by a postbaseline 
evaluation of alanime aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x 
ULN, along with total bilirubin (TBL) ≥ 2 x ULN and a non-elevated alkaline 


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phosphatase (ALP) < 2 x ULN, all based on blood draws collected within a 24-hour 
period. Patients who meet the potential Hy's Law criteria will be summarized. Supportive 
listing will also be provided. 
A listing of urine pregnancy test results will be provided for female subjects of child-
bearing potential with at least one positive result. 
10.4
Vital Signs
Vital sign measurements of systolic and diastolic blood pressures (sitting and standing), 
pulse rate (sitting and standing), respiratory rate, temperature, weight, orthostatic systolic 
blood pressure, orthostatic diastolic blood pressure, and orthostatic pulse rate will be 
summarized on Safety Populations 1 and 2.  
Each vital sign variable will be summarized for all time points (starting with Baseline) 
with the number of non-missing observations, mean and standard deviation, median, Q1, 
Q3, minimum and maximum. Mean change from baseline to each applicable post-baseline 
visit will be summarized for each vital sign variable, with the number of observations, 
baseline mean, and visit mean. The change from baseline mean, standard deviation, 
median, Q1, Q3, minimum and maximum will also be presented. 
Vital sign variables will be evaluated based on PCS criteria (Table 6). For each vital sign 
PCS criterion, the number and percentage of subjects who have a vital sign value meeting 
the criteria will be summarized. Listings will be provided to summarize subject-level vital 
sign data for subjects meeting PCS criteria.
10.5
Other Safety Analyses
10.5.1
Electrocardiogram
Descriptive statistics for ECG parameters (i.e., heart rate, PR interval, QRS interval, RR
interval, QT interval, and QTc interval) at baseline, postbaseline, and changes from 
baseline values at each postbaseline timepoint will be presented for the Safety Populations 
1 and 2. 


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ECG parameter values are considered PCS if ECG values meet either the actual value or 
change from baseline PCS high criteria listed in Table 7. The number and percentage of 
subjects with PCS postbaseline values will be summarized. The percentages will be 
calculated relative to the number of subjects with an available non-PCS baseline value and 
at least 1 postbaseline assessment. The numerator will be the total number of subjects with 
an available non-PCS baseline value and at least 1 PCS postbaseline ECG value during 
the study. A supportive listing of subjects with PCS postbaseline values will be provided. 
A listing of all AEs for participants with PCS ECG values will also be provided.
The number and percentage of subjects meeting each of the criteria for postbaseline ECG 
values of clinical interest listed in Table 5 will be summarized. Subjects will be counted 
only once for the most severe category. A supportive listing of participants with 
postbaseline QTcF increases > 30 msec will be provided, including the PID number, study 
center, and all QTc values (including changes from baseline). A listing of all AEs for 
participants with postbaseline QTcF increases > 30 msec will also be provided. 
A shift table from baseline to the end of open-label treatment period in the investigator's 
overall interpretation of the ECG will be presented for the following categories: normal; 
abnormal, not clinically significant; abnormal, clinically significant. A tabular display of 
subjects with postbaseline clinically significant ECG abnormalities according to the 
investigator's overall interpretation will be provided. 
10.5.2
Columbia-Suicide Severity Rating Scale
For C-SSRS, the number and percentage of subjects with suicidal ideation or suicidal 
behavior as recorded on the C-SSRS will be summarized for the Safety Populations 1 and 
2. The distribution of responses for most severe suicidal ideation and most severe suicidal 
behavior in the subject's lifetime history, in the past 6 months, in the open-label treatment 
period (atogepant treatment period, atogepant + ubrogepant treatment period, and overall), 
and in the follow-up period will also be presented. Supportive listings will be provided 
and will include the PID number, study center number, lifetime history, and postbaseline 


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values. Intensity of suicidal ideation and suicidal behavior type will also be included in 
these listings. 
10.6
Safety Subgroup Analyses
Two subgroups will be applied in subgroup analyses based on subjects' ubrogepant use: 
Subgroup by number of ubrogepant use days:
●
Never used ubrogepant 
●
Low ubrogepant use:  1-3 days of ubrogepant taken in the atogepant + 
ubrogepant treatment period 
●
Moderate ubrogepant use:  4-9 days of ubrogepant taken in the atogepant + 
ubrogepant treatment period
●
High ubrogepant use: >=10 days of ubrogepant taken in the atogepant + 
ubrogepant treatment period
Subgroup by number of ubrogepant doses taken:
●
Never used ubrogepant 
●
Low ubrogepant use: 1-6 doses of ubrogepant taken in the atogepant 
+ubrogepant treatment period
●
Moderate ubrogepant use: 7-18 doses of ubrogepant taken in the atogepant + 
ubrogepant treatment period
●
High ubrogepant use: 19+ doses of ubrogepant taken in the atogepant + 
ubrogepant treatment period
TEAE, serious TEAE, and TEAE leading to study drug discontinuation will be 
summarized by subgroups. 
11.0
Interim Analyses 
An interim analysis that includes all safety and efficacy analyses is planned when at least 
30 subjects have completed Visit 8 to support access/reimbursement negotiations. 


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11.1
Data Monitoring Committee  
An independent DMC will be established to review unblinded safety data and summary 
reports, identify any safety issues and trends, and make recommendations to AbbVie, 
including ongoing trial conduct or modifications to the trial, if emerging data show 
unexpected and clinically significant AEs of treatment.  
Details of the DMC memberships, standard operational procedures for data 
monitoring/review, frequency of review, and other pertinent details will be provided in a 
separate DMC Charter.  
12.0
Overall Type-I Error Control
No multiplicity adjustment for overall Type-I Error Control is planned for this study. 
13.0 
COVID-19 Related Analyses
This section specifies analyses related to COVID-19 pandemic from the following 
aspects: 
●
Disposition
●
Study visits and study procedures 
●
Protocol deviation  
●
Treatment interruption due to COVID-19 
●
TEAEs related with COVID-19 and supplemental signs and symptoms 
●
COVID-19 status (COVID-19 testing results or contact with a COVID-19 
positive person) 
●
COVID-19 vaccination
The Safety Populations 1 and 2 will be used for the planned analyses described above. 
The number of subjects with study visits impacted by COVID-19 will be summarized. In 
addition, the number of subjects impacted by COVID-19 and their corresponding 


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disposition status in the open-label periods and the follow-up period will be summarized 
respectively. 
The number of subjects who missed at least one entire visit, had in person, partial 
assessment done, and had virtual visits due to COVID-19 will be summarized.  
The number of subjects with protocol deviation due to COVID-19 will be provided. The 
number of subjects with study drug interruption due to COVID-19 will be provided as 
well. The number of subjects with TEAEs and serious TEAEs related to COVID-19 
vaccine will be provided.  
Supporting listings for the described analyses above and TEAEs leading to study 
discontinuation related to COVID-19 will be provided.  
14.0
Version History
This Statistical Analysis Plan (SAP) for Study M23-072 is based on the protocol dated 
22July2022. 
Table 1. 
SAP Version History Summary
Version
Date
Summary
1.0
31 March 2022
Initial version
2.0
07 December 2022
Corrected typos and removed duplicated paragraphs throughout the 
document. 
Changed "double-blind" to "open-label" throughout the document.
Updated language throughout the document to align with protocol.
Section 2.3 changed Week 1 to Day 1 to be consistent with 
protocol. 
Section 3.2 changed Weeks 12 to Weeks 13 to avoid overlap of 
visits.
Section 5.0 deleted 'Participants enrolled (randomized) in the 
study'. 
Section 5.0 changed 'follow-up period' to 'study' to correct the 
analysis of discontinuation period.
Section 9.3.2 deleted 'and the p-value'. No need to provide p-value 
in efficacy analyses for this open-label study.


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Version
Date
Summary
Added ubrogepant take dose subgroup definition in Section 9.4
Removed MMRM model-based analysis for under subgroup 
analysis for Section 9.4. 
Removed analysis in AESI section as it's covered in Section 10.3. 
Added subgroup analysis for safety (Section 10.6).
Updated Appendix A to clarify MTOQ6's definition.
Updated Appendix B, protocol deviation section to align with 
standard.
Removed Appendix C as AESIs are defined in the SAP body. 
Updated Appendix index accordingly.
Updated mITT 1 and mITT 2 population definitions with 
"received" instead of "receive" in Section 4.0. 
Added that baseline analyses are done for both Safety Population 1 
and Safety Population 2 in Section 4.0. 
Reorganized the subject categories in Section 5.0. Deleted analyses 
description that were repeated.
Added subject accountability by investigator in Section 5.0. 
Clarified definition for duration of treatment for both atogepant and 
ubrogepant and the analysis populations in Section 6.0. 
Specified demographic groups in Section 7.1. Added "migraine 
prevention medication in the past" to disease characteristics 
(migraine history) in Section 7.1. 
Added definitions for concomitant medication for each period in 
Section 7.3. 
Updated in Section 9.2 that efficacy analyses are based on observed 
case (OC).
Clarified the meaning of patient satisfaction responder in 
Section 9.3.2. 
In Section 9.4, added details about efficacy subgroup analyses and 
the analysis populations.
Deleted MedDRA version in Section 10.2.1 as it's repeated.
Specified that study drug include atogepant and ubrogepant in 
Section 10.2.2. 
Added analyses detail for Section 10.2.3 (TEAE by SOC & PT), 
Section 10.2.4 (SAE & AE leading to study drug discontinuation), 
and Section 10.3 (laboratory data).
Clarified potential Hy's law analysis in Section 10.3
For Section 13.0, deleted efficacy evaluation under COVID-19 
related analyses, specified the analysis populations, added TEAE 
leading to study discontinuation related to COVID-19.


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Version
Date
Summary
Moved ECG post-baseline values of clinical interest to appendix 
Table 8 (newly added). Changed the table numbering accordingly. 
15.0
References
1.
D'Antona L, Matharu M. Identifying and managing refractory migraine: barriers 
and opportunities? J Headache Pain. 2019;20(1):89. 
2.
Fischer MJ. The role of calcitonin gene-related peptide (CGRP) in the pathogenesis 
of primary headache. Drugs Fut. 2006;31(2):175-81. 
3.
Kenward MG, Roger JH. Small sample inference for fixed effects from restricted 
maximum likelihood. Biometrics. 1997;53(3):983-97.
4.
Ho TW, Connor KM, Zhang Y, et al. Randomized controlled trial of the CGRP 
receptor antagonist telcagepant for migraine prevention. Neurology. 
2014;83(11):958-66.  
5.
Kenward MG, Roger JH. Small sample inference for fixed effects from restricted 
maximum likelihood. Biometrics. 1997;53(3):983-97. 
6.
Pellesi L, Do TP, Ashina H, et al. Dual Therapy With Anti-CGRP Monoclonal 
Antibodies and Botulinum Toxin for Migraine Prevention: Is There a Rationale? 
Headache. 2020;60(6):1056-65. 


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Appendix A.
Derivation of Efficacy Variables
A.1 Derivation of Health Outcome Endpoints   
MSQ Related Endpoints Derivation 
MSQ v2.1 consists of 14 items with a 4-week recall period. The scoring of the MSQ is 
completed in following 3 steps.  
Step 1: Final item value assignment.
Precoded item values and final item values for each MSQ item response are shown 
in Table 2. 
Table 2. 
Item Values for MSQ Item Responses
Response Categories
Precoded Item Value
Final Item Value
None of the time
1 
6 
A little bit of the time
2 
5 
Some of the time
3 
4 
A good bit of the time
4 
3 
Most of the time
5 
2 
All of the time
6 
1 
Step 2: Computation of raw domain (dimension) scores 
Once a final item value has been assigned to each item, a raw score can be 
computed for each MSQ domain. Role Function Restrictive domain includes Items 
1 - 7, Role Function Preventive domain includes Items 8 - 11, and Emotional 
Function domain includes Items 12 - 14. The raw score for each domain is the 
algebraic sum of the final item values for all items in that domain. 
Missing data handling: if a respondent answered at least half of the items in a 
domain (or half plus one in the case of scales with an odd number of items), a 


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missing item value can be estimated using the average of the other completed 
items within the same dimension.
In detail, for MSQ v2.1 Role Function Restrictive domain, the 7 individual item 
responses using final item value will be summed, resulting in the raw domain 
score ranging from 7 to 42 with higher scores indicating better quality of life. If 
there are missing item responses, the raw domain score will be calculated by 
summing the non-missing item responses using final item value and dividing by 
the number of non-missing items and then multiplying by 7 provided that 4 or 
more items in the domain are completed; otherwise it will be set to missing. For 
MSQ v2.1 Role Function Preventive and Emotional domains, the raw domain 
scores will be calculated similarly using final item value respectively. If there are 
missing item responses, the corresponding raw domain score will be calculated by 
summing the non-missing item responses using final item value and dividing by 
the number of non-missing items and then multiplying by the number of questions 
in that domain provided that 2 or more domain items are completed; otherwise it 
will be set to missing. 
Step 3: Linear transformation to a 0 to 100 scale. 
The transformation formula for each MSQ 2.1 domain is listed below 
●Role Function -Restrictive:
(𝑟𝑟𝑟𝑟𝑟𝑟𝑠𝑠𝑠𝑠𝑠𝑠𝑟𝑟𝑠𝑠−7)∗100
35
●Role Function-Preventive:
(𝑟𝑟𝑟𝑟𝑟𝑟𝑠𝑠𝑠𝑠𝑠𝑠𝑟𝑟𝑠𝑠−4)∗100
20
●Emotional Function: 
(𝑟𝑟𝑟𝑟𝑟𝑟𝑠𝑠𝑠𝑠𝑠𝑠𝑟𝑟𝑠𝑠−3)∗100
15
HIT-6 Total Score Derivation 
For HIT-6 total score, pre-coded item values and final item values for each item response 
are shown in Table 3. Total score is calculated by summing 6 sub-item responses, 
resulting in the total score ranging from 36 to 78 with higher scores indicating greater 
impact. If any sub item is missing, then total score will be missing.


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Table 3. 
Item Values for HIT-6 Item Responses
Response Categories
Precoded Item Value
Final Item Value
Never
0 
6 
Rarely
1 
8 
Sometimes
2 
10
Very Often
3 
11
Always
4 
13
The HIT-6 instrument has a recall period of 4 weeks for 3 of the 6 items. 
Patient Health Questionnaire (PHQ-4) 
The PHQ-4 is a 4-item patient health questionnaire for anxiety and depression. Subjects 
are asked to indicate the frequency with which they have been bothered by 4 symptoms of 
depressive disorders over the previous 2 weeks, on a 4-point scale: 0 (not at all), 1 
(several days), 2 (more than half the days), and 3 (nearly every day). The total score 
ranges from 0 to 12 (from best to worst). A Total Score will be calculated using (sum of 
non-missing items) × 4 /(number of non-missing items) if 3 or more items scores have 
non-missing responses.  
MTOQ 6 Score Derivation
The MTOQ-6 is a 6 question, Likert-type, self-reporting questionnaire with responses 
ranging from "never" to "half the time or more" with the following response scores: Never 
= 1, Rarely = 2, Less Than Half The Time = 3, Half The Time Or More = 4. The total 
score for the MTOQ-6 is the sum of each response score and will be treated as missing if 
the response is missing for one or more questions. 
  


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WPAI:MIGRAINE Related Endpoints Derivation  
WPAI outcomes are expressed as impairment percentages, with higher numbers indicating 
greater impairment and less productivity, i.e., worse outcomes, as follows: 
Questions:  
●Q1 = currently employed (working for pay). 
●Q2 = missed work hours because of problems associated with your migraine 
●Q3 = missed work hours due to other reason. 
●Q4 = hours actually worked. 
●Q5 = migraine affected productivity while working. 
●Q6 = migraine affected regular daily activity.
Scores:
Multiply scores by 100 to express in percentages. 
●
Percent work time missed due to migraine (absenteeism): Q2/(Q2 + Q4)
●
Percent impairment while working due to migraine (presenteeism): Q5/10
●
Percent overall work impairment due to migraine (overall work productivity 
loss): Q2/(Q2 + Q4) + (1- (Q2/(Q2 + Q4))) × (Q5/10)
●
Percent activity impairment due to migraine (regular activity impairment): 
Q6/10 
If the response to Q1 ("Currently employed?") is No or missing, absenteeism, 
presenteeism, and overall work productivity loss will all be set to missing. 


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Appendix B.
Protocol Deviations 
The number and percentage of subjects who reported at least one of the following 
protocol deviation categories will be provided for the Safety Population 1.  
●Subject entered into the study even though s/he did not satisfy entry criteria.  
●Subject developed withdrawal criteria during the study and was not withdrawn.  
●Subject received wrong treatment or incorrect dose of study.  
●Subject took prohibited concomitant medication. 


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Appendix C.
Potentially Clinically Significant Criteria for Safety
The potentially clinically significant criteria for clinical laboratory parameters, vital signs 
and ECG parameters are provided in the following tables.  
Clinical laboratory parameters are provided in the following tables.
Table 4. 
Potentially Clinically Significant Criteria for Clinical Laboratory 
Parameters
PCS Criteria
Category
Parameter
SI Unit
PCS Low
PCS High
Chemistry
Albumin
g/L
< 0.8 × LLN
> 1.2 × ULN
Alanine aminotransferase
U/L
— 
≥ 3.0 × ULN
Alkaline phosphatase
U/L
— 
≥ 3.0 × ULN
Aspartate aminotransferase
U/L
— 
≥ 3.0 × ULN
Bicarbonate
mmol/L
< 0.9 × LLN
> 1.1 × ULN
Bilirubin, total
μmol/L
— 
≥ 1.5 × ULN
Blood urea nitrogen
mmol/L
— 
> 1.5 × ULN
Calcium
mmol/L
< 0.9 × LLN
> 1.1 × ULN
Chloride
mmol/L
< 0.9 × LLN
> 1.1 × ULN
Cholesterol, total
mmol/L
— 
> 1.6 × ULN
Creatinine
μmol/L
— 
> 1.5 × ULN
Creatine kinase
U/L
— 
> 2.0 × ULN
Estimated glomerular filtration 
rate
mL/min/1.73m2
< 60 
mL/min/1.73m2
— 
Glucose, nonfasting
mmol/L
< 0.8 × LLN
> 2.0 × ULN
Lactate dehydrogenase (LDH)
U/L
— 
> 3.0 × ULN
Phosphorus
mmol/L
< 0.9 × LLN
> 1.1 × ULN
Potassium
mmol/L
< 0.9 × LLN
> 1.1 × ULN
Protein, total 
g/L
< 0.9 × LLN
> 1.1 × ULN
Sodium
mmol/L
< 0.9 × LLN
> 1.1 × ULN
Triglycerides
mmol/L
— 
> 2.0 × ULN
Uric acid 
μmol/L
— 
> 1.2 × ULN


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PCS Criteria
Category
Parameter
SI Unit
PCS Low
PCS High
Hematology
Basophils, absolute cell count
109/L
— 
> 2.0 × ULN
Eosinophils, absolute cell 
count
109/L
— 
> 2.0 × ULN
Hematocrit
Ratio
< 0.9 × LLN
> 1.1 × ULN
Hemoglobin
g/L
< 0.9 × LLN
> 1.1 × ULN
Lymphocytes, absolute cell 
count
109/L
< 0.7 × LLN
> 1.3 × ULN
Monocytes, absolute cell 
count
109/L
< 0.5 × LLN
> 2.0 × ULN
Neutrophils, absolute cell 
count
109/L
< 0.7 × LLN
> 1.3 × ULN
Platelet count
109/L
< 0.5 × LLN
> 1.5 × ULN
Red blood cell count
1012/L
< 0.9 × LLN
> 1.1 × ULN
White blood cell count
109/L
< 0.9 × LLN
> 1.5 × ULN
Urinalysis
pH
pH
< 0.9 × LLN
> 1.1 × ULN
Glucose
mmol/L
— 
Positive1
Protein 
g/L
— 
Positive2
Specific gravity
— 
— 
> 1.1 × ULN
LLN = lower limit of normal value; ULN = upper limit of normal value; normal value provided by laboratory; SI = Le 
Système International d'Unités (International System of Units)
1.
Any results other than negative will be considered as positive.
2.
Any results other than trace or negative will be considered as positive.
Table 5. 
Criteria for Hepatic Laboratory Abnormalities
Laboratory Parameter
Categories
ALT
≥ 1 × ULN
≥ 1.5 × ULN
≥ 2 × ULN
≥ 3 × ULN
≥ 5 × ULN
≥ 10 × ULN
≥ 20 × ULN


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Laboratory Parameter
Categories
AST
≥ 1 × ULN
≥ 1.5 × ULN
≥ 2 × ULN
≥ 3 × ULN
≥ 5 × ULN
≥ 10 × ULN
≥ 20 × ULN
ALT or AST
≥ 1 × ULN
≥ 1.5 × ULN
≥ 2 × ULN
≥ 3 × ULN
≥ 5 × ULN
≥ 10 × ULN
≥ 20 × ULN
Bilirubin Total
≥ 1 × ULN
≥ 1.5 × ULN
≥ 2 × ULN
≥ 3 × ULN
≥ 5 × ULN
≥ 10 × ULN
≥ 20 × ULN
Alkaline Phosphatase
≥ 1 × ULN
≥ 1.5 × ULN
≥ 2 × ULN
≥ 3 × ULN
≥ 5 × ULN
≥ 10 × ULN
≥ 20 × ULN
Concurrent Elevations1
ALT or AST ≥ 3 × ULN and Bilirubin Total ≥ 1.5 × ULN
ALT or AST ≥ 3 × ULN and Bilirubin Total ≥ 2 × ULN
Potential Hy's Law1
ALT or AST ≥ 3 × ULN and Bilirubin Total ≥ 2 × ULN 
and ALP < 2 × ULN


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ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBL = total bilirubin; ALP = alkaline phosphatase; 
ULN = upper limit of normal (value provided by the laboratory)
1. 
Elevations are from the same day. 
Vital sign values will be considered PCS if they meet both the observed value criterion 
and the change from baseline value criterion, if both criteria are available, or meet either 
the observed value criterion or the change from baseline value criterion that is detailed in 
the following table. 
Table 6. 
Potentially Clinically Significant Criteria for Vital Signs 
Parameters
Parameter
Flag
Criteria
Observed Value
Change from Baseline
Systolic blood pressure, mm Hg
High
≥ 180
Increase of ≥ 20
Low
≤ 90
Decrease of ≥ 20
Diastolic blood pressure, mm Hg
High
≥ 105
Increase of ≥ 15
Low
≤ 50
Decrease of ≥ 15
Pulse rate, bpm
High
≥ 120
Increase of ≥ 15
Low
≤ 50
Decrease of ≥ 15
Weight, kg
High
— 
Increase of ≥ 7%
Low
— 
Decrease of ≥7%
Orthostatic SBP change, mm Hg
Low
≤ -20
— 
Orthostatic DBP change, mm Hg
Low
≤ -15
— 
Orthostatic Pulse rate change, bpm
High
≥ 25
— 
SBP = Systolic blood pressure; DBP = Diastolic blood pressure; bpm = beats per minute
ECG parameter values are considered PCS if ECG values meet either the actual value or 
change from baseline PCS high criteria listed in the following table.


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Table 7. 
Potentially Clinically Significant Criteria for ECG Parameters
Parameter
Unit
Criterion
QRS interval
msec
≥ 150
PR interval
msec
≥ 250
QTc (QTcB or QTcF) interval 
msec
> 500
QTc (QTcB or QTcF) interval
msec
Increase from baseline > 60
Table 8. 
ECG Post-baseline Values of Clinical Interest
Parameter
Unit
Criterion
QTcF interval
msec
> 450
> 480
> 500
Increase > 30 but ≤ 60
Increase > 60


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Appendix D.
Laboratory Parameters in Conventional Unit 
All clinical laboratory parameters will be reported in the International System (SI) units as
standard practice. In addition, descriptive statistics for values and changes from baseline
in conventional units at all assessed visits will be reported for selected laboratory 
parameters as listed in the following table.
Table 9. 
List of Selected Parameters Reported in Conventional Unit 
Number
Laboratory Parameter
Conventional Unit
Decimal Places
1 
Alanine Aminotransferase (SGPT)
U/L
0 
2 
Albumin
g/dL
1 
3 
Alkaline Phosphatase
U/L
0 
4 
Aspartate Aminotransferase (SGOT)
U/L
0 
5 
Bilirubin, Direct (Conjugated)
mg/dL
1 
6 
Bilirubin, Indirect (Unconjugated)
mg/dL
1 
7 
Bilirubin, Total
mg/dL
1 
8 
Blood Urea Nitrogen
mg/dL
0 
9 
Calcium
mg/dL
1 
10
Cholesterol, HDL
mg/dL
0 
11
Cholesterol, LDL 
mg/dL
0 
12
Cholesterol, LDL direct and calculated 
(combined)
(This lab parameter could be the same as #11) 
mg/dL
0 
13
Cholesterol, Total
mg/dL
0 
14
Creatine Kinase
U/L
0 
15
Creatinine
mg/dL
1 
16
Glucose
mg/dL
0 
17
Insulin
µIU/mL
1 
18
Triglycerides
mg/dL
0 
19
Uric Acid
mg/dL
1 
20
Hemoglobin
g/dL
1 


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Patient narratives will also include the values in conventional units for the selected lab
parameters in below table. That will be accomplished by presenting the values in 
conventional units within the parentheses next to the values in SI units.  
Table 10. 
Presenting Laboratory Data Using SI and Conventional Units in 
Narratives
LABORATORY DATA
Lab Test
Test Name
Normal Range
VISIT01
VISIT05
VISIT07
Low
High
2012-07-03
2012-08-07
2012-09-04
CHEMISTRY
Bilirubin, 
Total 
(µmol/L 
(mg/dL))
0 (0)
18.81 
(1.1)
6.84 (0.4)
5.13 (0.3)
5.13 (0.3)


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Appendix E.
List of Abbreviations 
Abbreviation/Term
Definition
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
C-SSRS
Columbia–Suicide Severity Rating Scale
DSMB
Data Safety Monitoring Board
eCRF 
electronic case report form
ECG 
electrocardiogram, electrocardiographic
EM
episodic migraine
EOS
end of study
ET
early termination
IWRS 
interactive web response system
LLN
lower limit of normal value
LSM
least squares mean
MedDRA
Medication Dictionary for Regulatory Activities
mITT
modified intent-to-treat
MMRM
mixed-effects model for repeated measures
PCS 
potentially clinically significant
PT
preferred term
Q1
first quartile (25th percentile of the data)
Q3
third quartile (75th percentile of the data)
QD
once daily
QTc
QT interval corrected for heart rate
QTcB
QT interval corrected for heart rate using the Bazett formula (QTcB = QT/(RR)½) 
QTcF
QT interval corrected for heart rate using the Fridericia formula (QTcF = QT/(RR)⅓) 
SAE
serious adverse event
SAP
statistical analysis plan
SI
Le Système International d'Unités (International System of Units)
SOC
standard of care
TBL 
total bilirubin
TEAE
treatment-emergent adverse event
ULN
upper limit of normal value
WHO
World Health Organization


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Appendix F.
Changes to Protocol-planned Analyses
There are no changes from the protocol-planned analyses.