Clinical trial NCT02873221
Conditions: Migraine, With or Without Aura
Sponsor: Allergan
Start date: 2016-09-13; Completion date: 2018-08-02
Enrollment: 1254 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will evaluate the long-term safety and tolerability of intermittent treatment with ubrogepant for the acute treatment of migraine over 1 year.

Detailed description:
Usual care is the open-label control arm. Dose of ubrogepant (50 mg or 100 mg) will be double-blind for active treatment arms.

Arms: arm 1: Usual Care as prescribed by the physician as standard of care in clinical practice for the treatment of migraine attacks for up to 1 year. arm 2: Ubrogepant 50 mg tablet orally plus placebo-matching ubrogepant tablet for the treatment of a qualifying migraine attack for up to 8 treatments every 4 weeks for up to 1 year. Participants may choose to take a second dose orally after the initial dose if migraine continues or returns. arm 3: Ubrogepant 100 mg (two 50 mg tablets) orally for the treatment of a qualifying migraine attack for up to 8 treatments every 4 weeks for up to 1 year. Participants may choose to take a second dose orally after the initial dose if migraine continues or returns.
Interventions: intervention 1: Ubrogepant intervention 2: Placebo-matching Ubrogepant intervention 3: Usual Care
Intervention descriptions: intervention 1: Ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack. intervention 2: Ubrogepant placebo-matching tablet orally for the treatment of a qualifying migraine attack. intervention 3: Treatment for a migraine as prescribed by the physician as standard of care in clinical practice.

Protocol documents:
Prot_000.pdf: 
NCT02873221 
 
 
Study ID: UBR‐MD‐04 
 
 
 
Title: A Multicenter, Randomized, Open‐Label Extension Study to Evaluate the Long‐Term Safety and 
Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine With or Without Aura 
 
 
Protocol Amd 3 Date: 11‐Apr‐2018 
 
 
 


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Title Page
ALLERGAN – CONFIDENTIAL
The following contains confidential, proprietary information which is the property of 
Allergan
A MULTICENTER, RANDOMIZED, OPEN-LABEL EXTENSION STUDY TO 
EVALUATE THE LONG-TERM SAFETY AND TOLERABILITY OF ORAL 
UBROGEPANT IN THE ACUTE TREATMENT OF MIGRAINE WITH OR WITHOUT 
AURA
Protocol Number:  
UBR-MD-04 Amendment 3
Phase:
3
Name of Investigational Product:
Ubrogepant
Sponsor:
Allergan Pharmaceuticals 
Authorized US Agent
International Limited
Allergan Sales, LLC
Clonshaugh Industrial Estate
2525 Dupont Drive
Coolock
Irvine, California USA  92612
Dublin 17
+1-714-246-4500
Ireland
+1-800-347-4500
Emergency Telephone Number(s):
Refer to the Study Contacts Page
Serious Adverse Event Reporting 
Fax Number:
Allergan Medical Safety Physician 
Contact Information:
Please see Study Contact Sheet
Allergan Signatory:
Original Protocol Date:
02 May 2016
Protocol Amendment 1 Date: 
15 Nov 2016
Protocol Amendment 2 Date: 
06 Dec 2017
Protocol Amendment 3 Date:
11 Apr 2018
The following information can be found on FDA Form 1572 and/or study contacts page:  
Name and contact information of Allergan study personnel and Emergency Telephone 
Numbers; name, address, and statement of qualifications of each investigator; name of each 
subinvestigator working under the supervision of the investigator; name and address of the 
research facilities to be used; name and address of each reviewing IRB; US 21 CFR 312.23 
section 6(iii)b.


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INVESTIGATOR SIGNATURE PAGE
INVESTIGATOR:
I agree to:

Implement and conduct this study diligently and in strict compliance with the 
protocol, good clinical practices and all applicable laws and regulations.

Maintain all information supplied by Allergan in confidence and, when this 
information is submitted to an Institutional Review Board (IRB), Independent Ethics 
Committee (IEC) or another group, it will be submitted with a designation that the 
material is confidential.

Ensure that all persons assisting with the trial are adequately informed about the 
protocol, the investigational product(s), and their trial-related duties and functions.
I have read this protocol in its entirety and I agree to all aspects.
Investigator Printed Name
Signature
Date


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Table of Contents
Title Page .................................................................................................................................. 1
Table of Contents...................................................................................................................... 3
List of Tables ............................................................................................................................ 6
Protocol Summary .................................................................................................................... 8
1.
Background and Clinical Rationale................................................................................. 13
2.
Study Objectives and Clinical Hypotheses...................................................................... 15
2.1
Study Objectives .................................................................................................... 15
2.2
Clinical Hypothesis................................................................................................ 15
3.
Study Design.................................................................................................................... 15
3.1
Adjudication Committee and Data Safety Monitoring Board................................ 16
4.
Study Population and Entry Criteria................................................................................ 16
4.1
Number of Patients................................................................................................. 16
4.2
Study Population Characteristics ........................................................................... 16
4.3
Inclusion Criteria.................................................................................................... 17
4.4
Exclusion Criteria................................................................................................... 17
4.5
Permissible and Prohibited Medications/Treatments............................................. 18
4.5.1
Permissible Medications/Treatments ...................................................... 18
4.5.1.1
Acute Treatment/Rescue Medication................................ 19
4.5.1.2
Definition of Females of Childbearing Potential and/or 
Acceptable Contraceptive Methods .................................. 20
4.5.2
Prohibited Medications/Treatments ........................................................ 20
4.5.3
Special Diet or Activities ........................................................................ 21
5.
Study Treatments............................................................................................................. 21
5.1
Study Treatments and Formulations ...................................................................... 21
5.2
Control Treatment.................................................................................................. 21
5.3
Methods for Masking/Blinding.............................................................................. 21
5.4
Treatment Allocation Ratio and Stratification....................................................... 22
5.5
Method for Assignment to Treatment Groups/Randomization.............................. 22
5.6
Treatment Regimen and Dosing............................................................................. 23
5.6.1
Ubrogepant .............................................................................................. 23
5.6.2
Usual Care ............................................................................................... 23


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5.6.3
Optional Second Dose and Rescue Medication ...................................... 24
5.7
Storage of Investigational Products/Treatments .................................................... 24
6.
Response Measures and Summary of Data Collection Methods..................................... 24
6
6.2
Safety Measures ..................................................................................................... 26
6.2.1
Adverse Events........................................................................................ 26
6.2.2
Events of Clinical Interest ....................................................................... 27
6.2.3
Clinical Laboratory Determinations........................................................ 27
6.2.4
Vital Sign Measurements ........................................................................ 28
6.2.5
Physical Examinations ............................................................................ 28
6.2.6
Electrocardiograms.................................................................................. 28
6.2.7
Suicidality Assessment............................................................................ 29
6.2.8
Cardiovascular Disease Risk................................................................... 29
6.3
Other Study Supplies ............................................................................................. 30
6.4
Summary of Methods of Data Collection .............................................................. 30
7.
Statistical Procedures....................................................................................................... 30
7.1
Analysis Populations.............................................................................................. 30
7.1.1
Modified Intent-to-Treat Population ....................................................... 30
7.1.2
Safety Population .................................................................................... 31
7.2
Collection and Derivation of Efficacy Assessments.............................................. 31
7.3
Hypothesis and Methods of Analysis..................................................................... 32
7.3.2
Safety Analyses ....................................................................................... 33
7.3.2.1
Adverse Events.................................................................. 34
7.3.2.2
Cardiovascular Risk .......................................................... 35
7.3.2.3
Clinical Laboratory Parameters......................................... 35
7.3.2.4
Vital Sign Measurements.................................................. 36
7.3.2.5
Electrocardiogram............................................................. 37
7.3.2.6
Suicidality Assessment...................................................... 37
7.3.2.7
Potential Hy’s Law............................................................ 37
7.4
Subgroup Analyses ................................................................................................ 38
7.6
Interim Analyses .................................................................................................... 38
8.
Study Visit Schedule and Procedures.............................................................................. 39


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8.1
Patient Entry Procedures........................................................................................ 39
8.1.1
Overview of Entry Procedures ................................................................ 39
8.1.2
Informed Consent and Patient Privacy.................................................... 39
8.5
Instructions for the Patients.................................................................................... 44
8.6
Unscheduled Visits ................................................................................................ 44
8.7
Compliance with Protocol...................................................................................... 44
8.8
Early Discontinuation of Patients .......................................................................... 45
8.9
Withdrawal Criteria................................................................................................ 45
8.10 Study Termination.................................................................................................. 46
9.
Adverse Events ................................................................................................................ 46
9.1
Definitions.............................................................................................................. 46
9.1.1
Adverse Event ......................................................................................... 46
9.1.2
Serious Adverse Event ............................................................................ 47
9.1.3
Severity.................................................................................................... 47
9.1.4
Relationship to Study Drug or Study Procedure ..................................... 48
9.2
Procedures for Reporting Adverse Events............................................................. 48
9.3
Procedures for Reporting a Serious Adverse Event............................................... 48
9.4
Exposure to Investigational Product During Pregnancy........................................ 49
9.5
ALT or AST Elevations ......................................................................................... 49
9.6
Potential Hy’s Law Cases ...................................................................................... 51
9.7
Procedures for Unmasking of Investigational Product .......................................... 51
10. Administrative Items ....................................................................................................... 52
10.1 Protection of Human Patients................................................................................. 52
10.1.1
Compliance with Informed Consent Regulations (US 21 CFR Part 50) 
and Relevant Country Regulations.......................................................... 52
10.1.2
Compliance with IRB or IEC Regulations.............................................. 52
10.1.3
Compliance with Good Clinical Practice ................................................ 52


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10.1.4
Compliance with Electronic Records; Electronic Signatures.................. 52
10.1.4.1
Regulations (US 21CFR Part 11)...................................... 52
10.2 Changes to the Protocol ......................................................................................... 53
10.3 Patient Confidentiality ........................................................................................... 53
10.3.1
Patient Privacy......................................................................................... 53
10.4 Documentation....................................................................................................... 53
10.4.1
Source Documents................................................................................... 53
10.4.2
Case Report Form Completion................................................................ 54
10.4.3
Study Summary....................................................................................... 55
10.4.4
Retention of Documentation ................................................................... 55
10.5 Labeling, Packaging, and Return or Disposal of Investigational 
Products/Treatments............................................................................................... 55
10.5.1
Labeling/Packaging................................................................................. 55
10.5.2
Clinical Supply Inventory ....................................................................... 56
10.5.3
Return or Disposal of Investigational Products/Treatments and/or 
Supplies ................................................................................................... 56
10.6 Monitoring by Allergan.......................................................................................... 56
10.7 Handling of Biological Specimens/Samples.......................................................... 56
10.8 Publications............................................................................................................ 57
10.9 Coordinating Investigator....................................................................................... 57
11. References........................................................................................................................ 57
12. Attachments..................................................................................................................... 59
12.1 Examination Procedures, Tests, Equipment, and Techniques ............................... 59
12.1.1
International Classification of Headache Disorders, 3rd Edition, Beta 
Version .................................................................................................... 59
12.2 Examples of Prohibited Medications ..................................................................... 75
12.3 Glossary of Abbreviations ..................................................................................... 78
12.4 Protocol Amendment 1 Summary.......................................................................... 81
12.5 Protocol Amendment 2 Summary.......................................................................... 88
12.6 Protocol Amendment 3 Summary.......................................................................... 92
List of Tables


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Table 2
Treatments Administered for Initial and Optional Second Dose.................... 23
Table 3
Clinical Laboratory Parameters ...................................................................... 28


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Protocol Summary
Study Compound:  Ubrogepant
Phase: 3
Study Objective:  To evaluate the safety and tolerability of intermittent treatment with ubrogepant for the 
acute treatment of migraine over 1 year
Clinical Hypotheses:  Ubrogepant 50 and 100 mg is safe and tolerable for the acute treatment of migraine 
over 1 year
Study Design
Structure: multicenter, randomized, open-label, 52-week extension study
Duration: 52 weeks
Study Treatment Groups: usual care, ubrogepant 50 mg, or ubrogepant 100 mg
Controls:  Not applicable
Dosage/Dose Regimen: Patients randomized to either of the ubrogepant arms will treat up to 8 migraine 
attacks (of any pain severity) per every 4-week period at home for a total of 1 year. Patients have the option 
to take a second dose of ubrogepant if the patient has either a nonresponding migraine or a migraine 
recurrence. The second dose of ubrogepant will be identical to the first dose.
Patients randomized to the usual-care arm will be instructed to treat their migraine with medications that 
they routinely use to relieve a migraine attack.
 
 
 
 
Study Population Characteristics
Number of Patients:  Approximately 1200 patients will be randomized (400 patients per arm) from 
approximately 200 centers in the United States
Condition/Disease:  Migraine with or without aura
Key Inclusion Criteria:  To be eligible for study participation, patients must have completed 1 of the lead-in 
studies, UBR-MD-01 or UBR-MD-02, 
 
 
Key Exclusion Criteria:  Patients with clinically significant electrocardiogram (ECG), vital sign, physical 
examination, or laboratory abnormalities, or who require prohibited concomitant medications (see 
Section 4.5.2)
Response Measures
 
 
Safety:  AEs, physical examinations, clinical laboratory determinations, vital sign measurements, ECG
parameters, and the Columbia –Suicide Severity Rating Scale (C-SSRS)


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General Statistical Methods and Types of Analyses:  
 
 
 
 
 
 
The safety analyses will be performed using the Safety population and will include AEs, clinical laboratory 
evaluations, vital sign measurements, ECG parameters, and the C-SSRS. For each of the clinical, laboratory, 
vital sign, and ECG parameters, the last nonmissing safety assessment before the first dose in the lead-in 
study will be used as the baseline for all analyses of that safety parameter. Continuous variables will be 
summarized by the number of patients and mean, SD, median, minimum, and maximum values. Categorical 
variables will be summarized by number and percentage of patients.
 
 


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1.
Background and Clinical Rationale
What is Migraine and How Prevalent is It?
Migraine affects 18% of women and 6% of men in the United States with a peak prevalence 
occurring between the ages of 25 to 55 years. Approximately one-third of migraineurs have 
3 or more migraine headaches per month, and over half report severe impairment or the need 
for bed rest during an attack (Lipton 2007). In the United States, work loss due to migraine is 
estimated to cost ~$13 billion annually (Hu 1999). Prevalence is similar in Europe, with 
migraine headache affecting 17.6% of women and 8% of men (Stovner 2010). It is currently 
ranked by the World Health Organization as 19th among causes of disability (Katsarava 
2012). 
Migraine is typically characterized by attacks of throbbing, unilateral headache of moderate 
or severe pain intensity, associated with nausea, vomiting, and/or sensitivity to light 
(photophobia) and sound (phonophobia). In about 25% of individuals, migraine headache 
may be preceded by focal neurological dysfunction (aura). Improving the diagnosis and 
optimizing treatments for migraine have been recognized as critically important to reduce the 
global burden of migraine (Katsarava 2012).
Because there are no biological markers for migraine, diagnosis is based on clinical history, 
examination, and the exclusion of other headache disorders. Physicians apply clinical criteria 
to guide diagnoses and subsequent treatment. Episodic migraine is a syndrome diagnosis 
applied to patients with migraine (with or without aura) who have 1 to 14 headache days per 
month. Chronic migraine is a specific International Classification of Headache Disorders 
criteria, 3rd edition beta version (ICHD-3 beta) diagnosis applied to a subset of patients with 
≥ 15 headache days per month (ICHD-3 beta 2013; Katsarava 2012; Olesen 2006). 
What is CGRP and Its Relationship to Migraine?
Calcitonin gene-related peptide (CGRP) is a neuropeptide implicated in the pathophysiology 
of migraine. CGRP levels in the cranial venous outflow (ie, external jugular vein) are 
increased during a migraine attack (Goadsby 1993) and exogenously administered CGRP has 
been shown to trigger migraine-like headache in migraineurs. The majority (80 to 90%) of 
trigeminal Aδ fibers that innervate the dura contain CGRP, suggesting that these fibers may 
be involved in sterile neurogenic inflammation and migraine pain transmission. Furthermore, 
the CGRP receptor is present on human meningeal and cerebral blood vessels. These 
observations suggest that activation of the trigeminovascular system, with release of CGRP, 


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may play a key role in migraine pathogenesis and that inhibition of CGRP function may yield 
a novel therapeutic approach to treating migraine.
Establishment of CGRP Antagonism to Treat Migraine
The ability of CGRP antagonism to relieve pain in the acute treatment of migraine was 
established by using an intravenous (IV) formulation of olcegepant (Olesen 2004), and 
replicated by Merck & Co., Inc., with an oral formulation of telcagepant, a highly selective 
CGRP receptor antagonist (CGRP RA). In Phase 3 studies, telcagepant was superior to 
placebo in the primary endpoints of 2-hour pain freedom, 2-hour pain relief, and the absence 
of associated symptoms (photophobia, phonophobia, and nausea), as well as the key 
secondary endpoint of 24-hour sustained pain freedom (SPF) (Connor 2009). Serum alanine 
aminotransferase (ALT) increases were observed with telcagepant, as well as with a second 
CGRP antagonist, MK-3207. For this reason, the development of these compounds was 
stopped. 
What is Ubrogepant?
Ubrogepant, a novel CGRP receptor antagonist that is chemically distinct from both 
telcagepant and MK-3207, is now being developed for the acute treatment of migraine. 
Preclinical and clinical studies conducted to date for ubrogepant have shown no evidence of 
hepatotoxicity.
A Phase 2b clinical study was conducted, which compared 1, 10, 25, 50, and 100 mg doses of 
ubrogepant to placebo in the acute treatment of migraine. Overall, all the ubrogepant doses 
tested were well tolerated and the adverse event (AE) profile of all ubrogepant doses did not 
differ significantly from placebo. For the primary efficacy endpoint of pain freedom at 
2 hours, ubrogepant doses of 1 and 10 mg did not differ from placebo, but doses of 25, 50, 
and 100 mg were better than placebo. For the primary efficacy endpoint of pain relief at 
2 hours none of the ubrogepant doses differed from placebo, probably due to a high placebo 
response rate.
The absence of migraine-associated symptoms of photophobia, phonophobia, and nausea 
were assessed as key secondary endpoints. Ubrogepant doses of 50 and 100 mg were 
significantly better than placebo for absence of phonophobia and photophobia at 2 hours, 
whereas 25 mg did not differ from placebo. None of the ubrogepant doses differed from 
placebo for the endpoint of absence of nausea at 2 hours. Measures of sustained migraine 
headache relief (2 to 24 hours and 2 to 48 hours SPF and sustained pain relief) generally 
suggested that ubrogepant 50 mg and 100 mg were more effective than the 25 mg dose.


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This trial is being conducted to evaluate the long-term safety and tolerability of ubrogepant 
for the acute treatment of migraine.
The purpose of including the usual-care arm will be to contextualize any safety findings that 
may occur over the course of a year in the ubrogepant arms. In open-label designs without a 
comparator arm, it can be difficult to interpret any safety findings that may arise in the 
experimental treatment arm. The proposed inclusion of the usual-care arm in this study is 
intended to address this limitation. Because of the stated purpose of the usual-care arm, 
efficacy data will not be collected from patients randomized to this arm.
2.
Study Objectives and Clinical Hypotheses
2.1
Study Objectives
To evaluate the safety and tolerability of intermittent treatment with ubrogepant for the acute 
treatment of migraine over 1 year.
2.2
Clinical Hypothesis
Ubrogepant 50 and 100 mg is safe and tolerable for the acute treatment of migraine over 
1 year.
3.
Study Design
This multicenter, randomized, open-label, 52-week extension study will enroll approximately 
1200 patients from approximately 200 centers in the United States. Patients will be 
randomized (1:1:1) to 1 of the following 3 treatment groups: usual care, ubrogepant 50 mg, 
or ubrogepant 100 mg (400 patients per arm). The study is open-label; however, 
randomization to the ubrogepant arms (50 and 100 mg) will be blinded. If and when an 
interim analysis occurs, the doses will be unblinded (see Section 7.6).
Patients randomized to either of the ubrogepant arms will treat up to 8 migraine attacks (of 
any pain severity) per 4-week period at home for a total of 1 year. Patients have the option to 
take a second dose of ubrogepant or rescue medication if the patient has either a 
nonresponding migraine or a migraine recurrence. The second dose of ubrogepant will be 
identical to the first dose. For detailed information on migraine treatment regimens, including 
optional second dose and rescue medication, see Section 5.6.
Patients randomized to the usual-care arm will be instructed to treat their migraine with 
medication(s) that they routinely use to relieve a migraine attack. Their usual medication(s) 


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for acute treatment will be identified at Visit 1 and any changes throughout the study will be 
recorded in the electronic case report form (eCRF).
 
 
 
 
. 
The primary outcome is safety and tolerability. The planned safety assessments include 
collection of AEs, clinical laboratory determinations, ECGs, vital sign measurements, 
physical examinations, and the Columbia-Suicide Severity Rating Scale (C-SSRS). 
3.1
Adjudication Committee and Data Safety Monitoring Board
The Adjudication Charter will be established and will describe the process for the 
surveillance, monitoring, and adjudication by the Clinical Adjudication Committee of events 
of post-treatment elevations of ALT and/or aspartate aminotransferase (AST) ≥ 3 times the 
upper limit of normal (ULN) in the ubrogepant program. The purpose of this committee 
charter will be to provide a standardized process for the adjudication of data associated with 
these events in order to determine whether the elevation was due to ubrogepant or not, and to 
determine whether there was a confounding factor. 
An independent Data Safety Monitoring Board will also be established to review safety data 
and summary reports, identify any safety issues and trends, and make recommendations to 
the Allergan, including modification or early termination of a trial, if emerging data show 
unexpected and clinically significant adverse effects of treatment. 
4.
Study Population and Entry Criteria
4.1
Number of Patients 
Approximately 1200 patients will be randomized (400 patients per arm) from approximately 
200 centers in the United States.
4.2
Study Population Characteristics
This study will include adult patients with migraine with or without aura who completed 
Study UBR-MD-01 or UBR-MD-02.


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4.3
Inclusion Criteria
To be eligible to participate in the study, patients must meet the following criteria:
1. Written informed consent and patient privacy information (eg, Written Authorization 
for Use and Release of Health and Research Study Information) obtained from the 
patient prior to initiation of any study-specific procedures.
2. Completed Study UBR-MD-01 or Study UBR-MD-02.
 
 
 
4.4
Exclusion Criteria
Patients who meet any of the following criteria will not be eligible to participate in the study:
 
2. Requirement for any medication during the study that is on the list of prohibited 
concomitant medications (see Sections 4.5.2 and 12.2) that cannot be discontinued or 
switched to an allowable alternative medication.
 
 
 
 
 
 
 
 


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4.5
Permissible and Prohibited Medications/Treatments
4.5.1
Permissible Medications/Treatments
Medications that are not specifically prohibited are allowed, with the following clarifications 
and restrictions for patients taking ubrogepant. Note that for patients assigned to the 
usual-care arm, these restrictions do not apply.
The following medications are allowed during the study but are prohibited within 48 hours 
prior to taking ubrogepant:

any triptan

any ergot derivative

any opioid

any nonsteroidal anti-inflammatory drug (NSAID)

any other form of analgesic (including acetaminophen)

any antiemetic agent

any proton pump inhibitor


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The following medications are allowed during the study, but are prohibited within 24 hours 
prior to taking investigational product (IP):

any antacid

any H2 blocker
Examples of allowed but restricted medications listed above are displayed in Section 12.2.

Aspirin up to 325 mg/day is allowed for cardiac prophylaxis.

Daily use of pregabalin is allowed. 
Patients on a stable prescribed dose of selective serotonin reuptake inhibitors (SSRI) or 
serotonin norepinephrine reuptake inhibitors (SNRI) in the lead-in study should continue 
without change in dose throughout this study.
Patients on migraine prophylactic medication (eg, beta-blocker, tricyclic antidepressant, 
topiramate, valproic acid, botulinum toxin) in the lead-in study should continue without 
change in dose throughout this study.
Therapy considered necessary for the patient's welfare may be given at the discretion of the 
investigator. If the permissibility of a specific medication/treatment is in question, please 
contact Allergan.
4.5.1.1
Acute Treatment/Rescue Medication
Medications for acute treatment of migraine listed above may be taken during the study 
within the parameters noted in Section 4.5.1 for patients taking ubrogepant. 
 
 
 
 
 
 
 
 
 
 
 


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4.5.1.2
Definition of Females of Childbearing Potential and/or 
Acceptable Contraceptive Methods
For the purposes of this study, females will be considered of childbearing potential unless 
they are naturally postmenopausal (ie, no menses for 2 years) or permanently sterilized 
(ie, bilateral tubal ligation, bilateral salpingectomy, bilateral oophorectomy or hysterectomy).
For WOCBP who may participate in the study, the following methods of contraception, if 
properly used, are generally considered reliable:  hormonal contraceptives (ie, oral, patch, 
vaginal ring, injection, implant), male condom with intravaginal spermicide, diaphragm or 
cervical cap with spermicide, intrauterine device, vasectomized partner, or sexual abstinence.
For males who may participate in the study, the following methods of contraception, if 
properly used, are generally considered reliable: postbilateral vasectomy, barrier 
contraception, or sexual abstinence. Male participants must also refrain from donating sperm 
during the course of the study.
The investigator and each patient will determine the appropriate method of contraception for 
the patient during participation in the study.
If a female becomes pregnant during the study, the investigator will notify Allergan 
immediately after the pregnancy is confirmed, and the patient will be withdrawn from the 
study after appropriate safety follow-up. The investigator will (1) notify the patient’s 
physician that the patient was being treated with investigational drug ubrogepant, and 
(2) follow the progress of the pregnancy. The investigator must document the outcome of the 
pregnancy and provide a copy of the documentation to Allergan.
4.5.2
Prohibited Medications/Treatments
The following medications are prohibited throughout the study period for patients taking 
ubrogepant. Note that for patients assigned to the usual-care arm, these restrictions do not 
apply.

strong and moderate cytochrome P450 3A4 (CYP3A4) inhibitors, including but not 
limited to: systemic (oral/IV) itraconazole, ketoconazole, fluconazole, erythromycin, 
clarithromycin, telithromycin, diltiazem, verapamil, aprepitant, cyclosporine, 
nefazodone, cimetidine, quinine, and human immunodeficiency virus (HIV) protease 
inhibitors

strong and moderate CYP3A4 inducers, including but not limited to: barbiturates (eg, 
phenobarbital and primidone), systemic (oral/IV) glucocorticoids, nevirapine, 


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efavirenz, pioglitazone, carbamazepine, phenytoin, rifampin, rifabutin, and St. John’s 
wort

inhibitors of the breast cancer resistance protein (BCRP) transporter (eg, rifampin)

drugs with narrow therapeutic margins (eg, digoxin, warfarin)
Examples of prohibited medications in the classes noted above are displayed in 
Attachment 12.2.
The decision to administer a prohibited medication/treatment is done with the safety of the 
study participant as the primary consideration. When possible, Allergan should be notified 
before the prohibited medication/treatment is administered.
4.5.3
Special Diet or Activities
Patients taking ubrogepant must refrain from consuming grapefruit or grapefruit juice from 
the time the consent form is signed until completion of the study. In addition, patients will be 
asked to refrain from sleeping and from consuming caffeine for at least 2 hours after they 
take IP.
Alcohol intake should be limited to no more than 3 drinks per 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.
5.
Study Treatments
5.1
Study Treatments and Formulations
Ubrogepant 
 oral compressed tablets containing 50 mg of 
ubrogepant.
Ubrogepant placebo
 tablets.
5.2
Control Treatment
This study does not include a control treatment.
5.3
Methods for Masking/Blinding
Ubrogepant will be provided to patients in the ubrogepant arms. A modified double-dummy 
design will be used to maintain the study blind for the ubrogepant arms. Patients randomized 


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to the ubrogepant arms will be provided IP in identical blister cards to maintain the blinding, 
and instructed to take 2 tablets to treat their migraine attack regardless of the dose group to 
which they are assigned. The patients randomized to the usual-care arm will not be dispensed 
ubrogepant.
5.4
Treatment Allocation Ratio 
Patients will be randomized (1:1:1) to 1 of the following 3 treatment groups: usual-care, 
ubrogepant 50 mg, or ubrogepant 100 mg. The study is open-label; however, randomization 
to the ubrogepant arms (50 and 100 mg) will be blinded. If and when an interim analysis 
occurs, the doses will be unblinded (see Section 7.6).
 
 
 
5.5
Method for Assignment to Treatment Groups/Randomization
Prior to initiation of study treatment, each patient who provides informed consent will be 
assigned a patient number that will serve as the patient identification number on all study 
documents.
At the time of randomization (ie, Visit 2), eligible patients will be randomly assigned to 1 of 
3 treatment arms in a 1:1:1 ratio to receive usual-care, ubrogepant 50 mg, or ubrogepant 
100 mg or 
 
.
An automated interactive web response system (IWRS) will be used to manage the 
randomization and treatment assignment. Allergan Biostatistics (randomization programmer) 
will prepare the randomization codes.
Investigational product will be labeled with medication kit numbers. The IWRS will provide 
the site with the specific medication kit number(s) for each randomized patient in the 
ubrogepant arms at the time of randomization. Sites will dispense IP according to the IWRS 
instructions. Sites will receive the IWRS confirmation notifications for each transaction. All 
notifications will be maintained with the study source documents.


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5.6
Treatment Regimen and Dosing
5.6.1
Ubrogepant
Table 2 presents the treatments that will be administered in this study. Patients randomized to 
the ubrogepant arms will be instructed to take 2 tablets to treat their migraine attack 
regardless of the dose group to which they are assigned.
Table 2
Treatments Administered for Initial and Optional Second Dose
Drug/Dose
Dose Frequency
Route of 
Administration
Investigational Product Administered
Initial Dose
Optional Second Dose
Ubrogepant 
50 mg
Up to 8 times/4 weeks for 
1 year (with optional 
second dose – maximum 
16 times/4 weeks)
Oral (tablet)
Ubrogepant 50 mg/ 
placebo 50 mg
Ubrogepant 50 mg/ 
placebo 50 mg
Ubrogepant 
100 mg
Up to 8 times/4 weeks for 
1 year (with optional 
second dose – maximum 
16 times/4 weeks)
Oral (tablet)
Ubrogepant 50 mg/ 
ubrogepant 50 mg
Ubrogepant 50 mg/ 
ubrogepant 50 mg
Patients randomized to the ubrogepant arms will be allowed to treat up to 8 qualifying 
migraine headaches (of any pain severity) per 4-week period throughout the course of a year. 
Patients will be instructed to treat the migraine headaches as soon as possible when all of the 
following conditions are met:

At least 48 hours since the last dose of ubrogepant

At least 48 hours of pain freedom (ie, no headache for at least 48 hours) 

The migraine headache started less than 4 hours ago

The migraine headache is not already resolving on its own

Prohibited medication has not been taken
5.6.2
Usual Care
Patients randomized to the usual-care arm will be instructed to treat their migraine with the 
medication(s) that they routinely take to relieve a migraine attack. Their usual medication(s) 
for acute treatment will be identified at Visit 1. At any time during the study, the patient’s 
treating physician or the investigator may instruct these patients to change their migraine 
treatment. Any changes to the usual medication(s) identified at Visit 1 will be recorded in the 


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eCRF. There will be no limitations to the number of migraines treated and no qualifiers to 
treat a migraine for patients in this arm. 
5.6.3
Optional Second Dose and Rescue Medication
Patients who took ubrogepant for their initial dose will have the opportunity to take an 
optional second dose of ubrogepant if they continue to have headache of any pain severity or 
if headache (of any pain severity) returns. An optional second dose can be taken from 2 to 
48 hours after the initial ubrogepant dose. 
 
 
 
 
 
 
 
 
 
 
 
 
5.7
Storage of Investigational Products/Treatments
Investigational product at the site must be stored at room temperature in a securely locked 
cabinet. Further details regarding the storage of the IP are in the Study Reference Manual.
6.
Response Measures and Summary of Data Collection Methods
 
 


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6.2
Safety Measures
6.2.1
Adverse Events
Subjective AEs will be collected throughout the study. For all AEs, the investigator must 
provide an assessment of the severity, causal relationship to the IP, start and stop date, and 
seriousness of the event (eg, serious adverse event [SAE]), document all actions taken with 
regard to the IP, and detail any other treatment measures taken for the AE. For events noted 
as SAEs, Allergan must be notified immediately to meet their reporting obligations to 
appropriate regulatory authorities (see Section 9.3). 


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6.2.2
Events of Clinical Interest
Selected nonserious and serious events are of clinical interest and will require immediate 
reporting, recording and follow-up. The following events will be closely monitored:

Suicidal ideations with intent, with or without a plan, (ie, Type 4 or 5 on the C-SSRS) 
or any suicidal behaviors 

Elevated ALT or AST laboratory value that is ≥ 3 times the ULN

Potential Hy’s law cases: elevated ALT or AST laboratory value that is ≥ 3 times the 
ULN and an elevated total bilirubin laboratory value that is ≥ 2 times the ULN and, at 
the same time, an alkaline phosphatase laboratory value that is < 2 times the ULN.
Reporting requirements for ALT or AST elevations and potential Hy’s law cases are outlined 
in Sections 9.5 and 9.6. Responses to the C-SSRS that meet the above criterion will be 
captured in the electronic tablet (eTablet) and monitored by Allergan. Events that are 
determined to be AEs or SAEs must be reported appropriately via the designated eCRF pages 
and forms.
6.2.3
Clinical Laboratory Determinations
Blood and urine samples for clinical laboratory tests will be collected at the visits outlined in 
Table 1. Hematology, chemistry, and urinalysis will be conducted at these visits. The 
investigator will assess the clinical significance of any values outside the reference ranges 
provided by the central laboratory. A central laboratory will be used to evaluate all urine and 
blood samples, which will be collected, processed, and stored according to the instructions 
provided by the laboratory. Patients with abnormalities judged to be clinically significant at 
Screening (Visit 1) will be excluded from the study. WOCBP will be required to have a urine 
pregnancy test at all visits. A positive pregnancy test at Visit 1 or Visit 2 will exclude the 
patient from participation in the study. Investigators may also perform unscheduled clinical 
laboratory determinations at any time for the purpose of patient safety. Patients are not 
required to fast overnight before coming in for their appointments. 
The clinical laboratory parameters to be measured are shown in Table 3.


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Table 3
Clinical Laboratory Parameters
Category
Parameter
Chemistry
Sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, 
creatinine, total bilirubin, alkaline phosphatase, aspartate aminotransferase, 
alanine aminotransferase, lactate dehydrogenase, creatine kinase, total protein, 
albumin, calcium, phosphorus, uric acid, total cholesterol, high density 
lipoprotein, low density lipoprotein, total triglycerides; the estimated glomerular 
filtration rate will be calculated by the central laboratory
Hematology
Hemoglobin; hematocrit; red blood cell count; red blood cell indices (mean 
corpuscular volume, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration); white blood cell count, including differential 
(neutrophils, lymphocytes, monocytes, eosinophils, and basophils); platelet count
Urinalysis
Urine dipstick for specific gravity, pH, protein, glucose, ketones, bilirubin, and 
blood; microscopic examination including red blood cells/high-power field, 
white blood cells/high-power field, and casts/low-power field
6.2.4
Vital Sign Measurements
Vital sign measurements, including sitting and standing BP, sitting and standing pulse rate, 
respiratory rate, temperature, and body weight will be taken, according to Table 1. Sitting 
and standing BP and pulse rate will be determined as follows: BP and pulse measurements 
will be performed after the patient sits quietly for 5 minutes, followed by a second set of 
measurements taken after the patient stands for 3 minutes (but no longer than 10 minutes).
6.2.5
Physical Examinations
A complete physical examination will be performed at the visits outlined in Table 1. A 
professionally trained physician or healthcare professional licensed to performed physical 
examinations will examine the patient for any detectable abnormalities of the following body 
systems: general appearance; neck (including thyroid); head, eyes, ears, nose, and throat; 
lungs; heart/cardiovascular; abdomen; neurologic; extremities; back; musculoskeletal; 
lymphatic; skin; and other. The neurologic examination should be conducted to detect the 
presence of any significant sensory/motor abnormalities.
6.2.6
Electrocardiograms
A 12-lead ECG will be performed at the visits outlined in Table 1. ECGs will be sent to a 
central ECG laboratory to be centrally read by a cardiologist. All ECGs should be performed 
after the patient has been supine for at least 5 minutes. A copy of the ECG will be saved as a 
source document. ECGs will be transmitted electronically to the central ECG laboratory for 
analysis according to the instructions provided by the laboratory. The overall interpretation 


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of the clinical significance of the ECG will be determined by the investigator and recorded in 
the patient’s eCRF in the source notes.
6.2.7
Suicidality Assessment
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation 
and behavior. Suicidal ideation is classified on a 5-item scale: Type 1 (wish to be dead), Type 
2 (nonspecific active suicidal thoughts), Type 3 (active suicidal ideation with any methods 
[not plan] without intent to act), Type 4 (active suicidal ideation with some intent to act, 
without specific plan), and Type 5 (active suicidal ideation with specific plan and intent). The 
C-SSRS also captures information about the intensity of ideation, specifically the frequency, 
duration, controllability, deterrents, and reasons for the most severe types of ideation. 
Suicidal behavior is classified on a 5-item scale: Type 0 (no suicidal behavior), Type 1 
(preparatory acts or behavior), Type 2 (aborted attempt), Type 3 (interrupted attempt), and 
Type 4 (actual attempt). More than 1 classification can be selected provided they represent 
separate episodes. For actual attempts only, the actual or potential lethality is classified for 
the initial, most lethal, and most recent attempts. The C-SSRS will be completed at all study 
visits. At all visits, the C-SSRS will be completed for ideation and behavior since the 
previous visit. The C-SSRS will be completed on the eTablet by the investigator or designee 
with current and valid training in administering the assessment. A patient should not be 
released from the study center until the results of C-SSRS are reviewed and it is confirmed 
that the patient is not considered to be at risk.
6.2.8
Cardiovascular Disease Risk
Patients will be classified to 1 of 3 coronary heart disease risk categories (low, moderate, 
high) based on the National Cholesterol Education Program (NCEP; NIH Publication 
No. 01-3670, 2001). 

Category 1 (High Risk): > 20% 10-year cardiovascular (CV) risk 

Category 2 (Moderate Risk): 10 to 20% 10-year CV risk 

Category 3 (Low Risk): < 10% 10-year CV risk
Risk of cardiovascular disease will be assessed in the lead-in studies using an algorithm 
based on NCEP and the Framingham risk factors, along with the presence of cardiovascular 
heart disease or other clinical forms of atherosclerotic disease, as well as diabetes.


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6.3
Other Study Supplies
The following will be provided by Allergan:

All supplies needed for blood and urine sampling (central laboratory analysis, urine 
culture/sensitivity), urine dipstick reagent strips, and urine pregnancy tests

Shipping materials for shipment of laboratory samples to central laboratory

All supplies needed for ECG assessment, including ECG machine

eDiary

eTablet
6.4
Summary of Methods of Data Collection
An IWRS will be used to randomize patients and manage ubrogepant inventory. Data for this 
study will be collected using eCRFs via an electronic data capture system. Source documents 
will be used at the sites and may include a patient’s medical record, hospital charts, clinic 
charts, the investigator’s patient study files, as well as the results of diagnostic tests, such as 
laboratory tests, ECGs, etc. Centralized vendors will be used for the analysis of all 
blood/urine samples and ECG assessments. Additional information on the collection and 
handling of samples is detailed in respective laboratory manuals. 
Patients in the ubrogepant arms will use an eDiary to record details associated with their 
migraine attack, 
 
. Patients in the usual-care arm will 
use the eDiary to record details associated with their migraine attack before it is treated with 
their usual medication.
The C-SSRS will be conducted as a clinical interview at each visit and recorded by a 
qualified site staff member via an eTablet.
7.
Statistical Procedures
7.1
Analysis Populations
7.1.1
Modified Intent-to-Treat Population
The Modified Intent-to-Treat (mITT) population will consist of all randomized patients who 
received at least 1 dose of IP (ubrogepant) and had at least 1 post-treatment efficacy 


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assessment in this study. The mITT population is only defined for the ubrogepant arms, as no 
efficacy measurements will be collected from patients in the usual-care arm.
7.1.2
Safety Population
The Safety population will be defined separately for the ubrogepant arms and the usual-care 
arm. 

Ubrogepant arms: All randomized patients who received ≥ 1 dose of treatment 

Usual-care arm: All randomized patients in the usual-care arm. 
The purpose of the usual-care arm is to contextualize any safety findings that may occur in 
the ubrogepant treated patients over the course of 12 months.  As such, data from all patients 
randomized to the usual-care arm, regardless of whether the patient used medication to treat 
migraine, will be included in the safety analyses.
 
 
 


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7.3
Hypothesis and Methods of Analysis
 
 
 
 
.


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7.3.2
Safety Analyses
The safety analyses will be performed using the Safety population. The safety parameters 
will include AEs, clinical laboratory evaluations, vital sign measurements, ECG parameters, 


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and the C-SSRS. For each of the clinical, laboratory, vital sign, and ECG parameters, the last 
nonmissing safety assessment before the first dose in the lead-in study will be used as the 
baseline for all analyses of that safety parameter. Continuous variables will be summarized 
by the number of patients and mean, SD, median, minimum, and maximum values. 
Categorical variables will be summarized by number and percentage of patients.
7.3.2.1
Adverse Events
AEs will be coded by system organ class and preferred term using the Medical Dictionary for 
Regulatory Activities. 
An AE will be considered a treatment-emergent adverse event (TEAE) if it was present after 
the first dose of treatment in the lead-in study or was present before the date of the first dose 
of treatment in the lead-in study and increased in severity after the first dose of treatment in 
the lead-in study. If more than 1 AE was reported before the first dose of treatment of the 
lead-in study and coded to the same preferred term, the AE with the greatest severity will be 
used for comparison with the AEs occurring after the first dose of treatment of the lead-in 
study. An AE that occurs after Visit 16 for patients with Visit 16, or more than 30 days after 
the last visit or last treatment, whichever is later, for patients without Visit 16 will not be 
considered as a TEAE. 
The number and percentage of patients reporting TEAEs after randomization in each 
treatment group will be tabulated by descending percentage in the highest dose group, by 
system organ class and preferred term, and further categorized by severity and causal 
relationship to the study treatment. If more than 1 AE is coded to the same patient, the patient
will be counted only once for that preferred term using the greatest severity and strictest 
causality for the summarization by severity and causal relationship. 
The incidence of common (≥ 2% of patients in any treatment group) TEAEs will be 
summarized by system organ class, preferred term, and treatment group. 
The total number of TEAEs by severity and causal relationship to the study treatment will be 
summarized by treatment group. 
A SAE that occurred between the date of the first dose of treatment in the lead-in study and 
Visit 16 for patients with Visit 16, or within 30 days after the last visit or last treatment, 
whichever is later, for patients without Visit 16, inclusive, will be considered an on-therapy 
SAE. The number and percentage of patients who have on-therapy SAEs after randomization 
will be summarized by preferred term and treatment group. 


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The number and percentage of patients who had AEs leading to premature discontinuation of 
the study treatment will be summarized by preferred term and treatment. 
For all screened patients, separate tabular displays will be presented for patients who died, 
patients with SAEs, and patients with AEs leading to premature discontinuation. 
The number and percentage of patients with TEAEs of clinical interest will be summarized 
by preferred term and treatment group. TEAEs of clinical interest include triptan-associated 
TEAEs, abuse-related TEAEs, hepatic injury TEAEs, cardiac arrhythmias TEAEs, central 
nervous system TEAEs, vascular disorders TEAEs, embolic and thrombotic events TEAEs, 
hypertension TEAEs, ischemic heart disease TEAEs, and suicide/self-injury TEAEs.
7.3.2.2
Cardiovascular Risk
Patients will be categorized into 1 of 3 coronary heart disease (CHD) risk subgroups based 
on National Cholesterol Education Program Adult Treatment Panel III Guidelines (NCEP 
ATP III) (Grundy 2004; NIH Publication No. 01-3670, 2001). An algorithm will be used for 
assigning patients to a CV risk category (low, moderate, or high risk) in the lead-in studies.
A summary of adverse experiences will be provided for the CV risk factor subgroups listed 
above. 
7.3.2.3
Clinical Laboratory Parameters
Descriptive statistics for clinical laboratory values (in SI units) and changes from the baseline 
values at each assessment timepoint will be presented by treatment group for clinical 
laboratory parameters. In addition, descriptive statistics for values and changes from the 
baseline values in conventional units at each assessment timepoint will be presented for 
selected clinical laboratory parameters. Patient narratives will also include the values in 
conventional units for the selected laboratory parameters. 
Clinical laboratory test values will be considered potentially clinically significant (PCS) if 
they meet either the lower-limit or higher-limit PCS criteria. PCS criteria will be specified in 
the Statistical Analysis Plan (SAP). The number and percentage of patients who have PCS 
postbaseline clinical laboratory values will be tabulated by treatment group. The percentages 
will be calculated relative to the number of patients with available non-PCS baseline values 
and at least 1 postbaseline assessment. The numerator will be the total number of patients 
with available non PCS baseline values and at least 1 PCS postbaseline value. A supportive 
tabular display of patients with PCS postbaseline values will be provided, including the 


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patient number, baseline, and all postbaseline (including non-PCS) values. In addition, a 
tabular display showing all AEs that occurred in patients who had PCS postbaseline clinical 
laboratory values will be provided.
Shift tables from baseline to end of study for clinical laboratory parameters will be presented 
by treatment group for the following categories: low, normal, and high, which are provided 
by the lab vendor.
Any post-treatment ALT and/or AST results that are ≥ 3 times the ULN are considered 
events of clinical interest in this study and are subject to blinded adjudication by the Clinical 
Adjudication Committee to determine whether the elevation is due to treatment or not, and to 
determine whether there is a confounding factor. Patients with liver function laboratory 
findings that meet predetermined criteria will be summarized by treatment group along with 
the adjudication results. A detailed listing of all patients with any liver function laboratory 
findings will be provided.
7.3.2.4
Vital Sign Measurements
Descriptive statistics for vital sign measurements (sitting and standing systolic and diastolic 
BP, sitting and standing pulse rate, respiratory rate, temperature, weight, and BMI) and 
changes from baseline values at each visit and at the end of study will be presented by 
treatment group.
Vital sign values will be considered PCS if they meet both the observed-value criteria and the 
change-from-baseline criteria. PCS criteria will be specified in the SAP. The number and 
percentage of patients with PCS postbaseline values will be tabulated by treatment group. 
The percentages will be calculated relative to the number of patients with available non-PCS 
baseline values and at least 1 postbaseline assessment. The numerator will be the total 
number of patients with available non-PCS baseline values and at least 1 PCS postbaseline 
value. A supportive tabular display of patients with PCS postbaseline values will be 
provided, including the patient number, baseline and all postbaseline (including non-PCS) 
values.
In addition, a tabular display showing all AEs that occurred in patients who had PCS 
postbaseline vital sign values will be provided.


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7.3.2.5
Electrocardiogram
Descriptive statistics for ECG parameters (heart rate, RR interval, PR interval, QRS interval, 
QT interval, and QTc) and changes from baseline values at each assessment timepoint to the 
end of study will be presented by treatment group. 
Electrocardiographic parameter values are considered PCS if they meet or exceed the 
higher-limit PCS criteria. PCS criteria will be specified in the SAP. The number and 
percentage of patients with PCS postbaseline ECG values will be tabulated by treatment 
group. The percentages will be calculated relative to the number of patients with available 
non-PCS baseline values and at least 1 postbaseline assessment. The numerator is the total 
number of patients with available non-PCS baseline values and at least 1 PCS postbaseline 
value. A supportive tabular display of patients with PCS postbaseline values will be 
provided, including the patient number, baseline, all postbaseline (including non-PCS) 
values, and change from baseline. In addition, a tabular display showing all AEs that 
occurred in patients who had postbaseline PCS ECG values will be provided.
A shift table from baseline to the end of study in the investigator’s overall interpretation of 
the ECG will be presented by treatment group for the following categories: normal,
abnormal, not clinically significant, abnormal, clinically significant. A tabular display 
showing patients with postbaseline clinically significant ECG abnormalities according to the 
investigator’s overall interpretation will be provided.
7.3.2.6
Suicidality Assessment
For the C-SSRS, the number of patients with suicidal ideation and suicidal behavior in 
lifetime history, during the treatment period, and during the Safety Follow-up period will be 
summarized by treatment group for the Safety population. Supportive tabular display of 
patients with all values will be provided, including patient number, treatment group, visit 
number, intensity of suicidal ideation, suicidal behavior type, and lethality of suicidal 
behavior. 
7.3.2.7
Potential Hy’s Law
Potential Hy’s Law criteria within a 24-hour window is defined by a postbaseline elevation 
of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the ULN, 
along with total bilirubin (TBL) ≥ 2 times the ULN and a nonelevated alkaline phosphatase 
(ALP) < 2 times the ULN, all based on blood draws collected within a 24-hour period.


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Potential Hy’s Law criteria without time window (evaluation of drug-induced serious 
hepatotoxicity [eDISH]) is defined by maximum of postbaseline elevation of ALT or AST 
≥3 times the ULN, along with maximum of postbaseline elevation of TBL ≥ 2 times the 
ULN.
Patients who meet the potential Hy’s Law criteria from randomization to Visit 16 will be 
summarized. Supportive tabular displays also will be provided. 
7.4
Subgroup Analyses
Subgroup analyses will be done for disposition, treatment exposure, and TEAEs for sex, age 
group (< 40 vs ≥40, and < 65 vs ≥65), race (white vs all other races), cardiovascular risk 
category, and renal function class.
 
 
 
 
 
 
7.6
Interim Analyses
The interim analysis for Study UBR-MD-04 will occur when at least 300 ubrogepant patients
(with a minimum of 2 migraines treated with ubrogepant per month, on average) have been 
enrolled in Study UBR-MD-04 for 6 months and 200 ubrogepant patients (with a minimum 
of 2 migraines treated with ubrogepant per month, on average) have been enrolled in 
Study UBR-MD-04 for 1 year. 
In regards to blinding, although this is an open-label study, randomization to the ubrogepant 
50 mg or 100 mg arms is blinded. If and when an interim analysis occurs, Allergan staff will 
be unblinded to the ubrogepant doses; however, patients and sites will remain blinded. The 
interim analysis will include all analyses specified in the SAP except for efficacy analyses.
Details regarding the interim analysis are specified in the SAP.


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8.
Study Visit Schedule and Procedures
Table 1 presents the schedule of visits and procedures. 
8.1
Patient Entry Procedures
8.1.1
Overview of Entry Procedures
Prospective patients as defined by the inclusion and exclusion criteria in Sections 4.3 and 4.4
who completed Study UBR-MD-01 or UBR-MD-02 will be considered for entry into this 
study.
8.1.2
Informed Consent and Patient Privacy
The study will be discussed with the patient and a patient wishing to participate must give 
informed consent prior to any study-related procedures or change in treatment. The patient 
must also give authorization and other written documentation in accordance with local 
privacy requirements (where applicable) prior to any study-related procedures or change in 
treatment.
Each patient that provides informed consent will continue using the patient number assigned 
in the lead-in study for documentation throughout the study.
 
 
 
 
 
 
 
 
 


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and
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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
 
 
 
 
 
 
 


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8.5
Instructions for the Patients
Section 4.5.3 provides diet and activity instructions for patients enrolled in the study. 
All patients will be instructed to use an electronic diary (eDiary) to record details associated 
with their migraine attack. Training for the eDiary will be provided for qualified patients at 
Visit 2. Patients will be instructed to bring their eDiary to each clinic visit and for those who 
were dispensed ubrogepant, return their medication packs (used and unused).
8.6
Unscheduled Visits
Additional examinations and laboratory assessments may be performed as necessary to 
ensure the safety and well-being of the patients during the study period. Unscheduled visit 
eCRFs should be completed for each unscheduled visit. For all parameters not measured, 
indicate “not done”.
8.7
Compliance with Protocol
All assessments will be conducted at the appropriate visits as outlined in Table 1, and the 
timing of the visits should occur as close as possible to the specified day. At each visit, the 
patient will be asked if he or she changed the dose/regimen of any existing concomitant 
medications or initiated the use of any new concomitant medications since the last visit, to 
ensure compliance with the protocol.
Patients will record the requested information regarding their migraine attack and ubrogepant 
taken in the eDiary. Ubrogepant compliance will be closely monitored by counting the 
number of tablets dispensed and returned. Every effort will be made to collect all unused 
ubrogepant.


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8.8
Early Discontinuation of Patients
A premature discontinuation will occur when a patient who signed the informed consent 
form (ICF) and was randomized ceases participation in the study, regardless of 
circumstances, before completion of the study. Patients can be prematurely discontinued 
from the study for 1 of the following reasons:

AE

Protocol violation

Noncompliance with ubrogepant

Withdrawal of consent (a clear reason must be documented)

Lost to follow-up (every effort must be made to contact the patient; a 
certified/traceable letter must be sent)

Lack of qualifying event (a qualifying migraine is not treated within 6 months)

Pregnancy

Other reasons
Patients may voluntarily withdraw from the study at any time. Notification of early patient 
discontinuation from the study and the reason for discontinuation will be made to Allergan 
and will be clearly documented on the appropriate eCRF. All randomized patients who 
prematurely discontinue from the study, regardless of cause, should be seen for a final 
assessment. A final assessment will be defined as completion of the evaluations scheduled 
for Visit 15/ ET. If the patient discontinues prematurely, the patient is expected to return for a 
Safety Follow-up visit 4 weeks after Visit 15/ET.
8.9
Withdrawal Criteria
Women who become pregnant will be withdrawn from the study (see Section 4.5.1.2) and 
should refrain from taking ubrogepant. The patient should return to the clinic for Visit 15/ET 
procedures.
Patients who meet IP discontinuation criteria related to abnormal liver function tests 
(Section 9.5) and who are advised not to be re-challenged will be withdrawn from the study.
Patients who reply with “yes” to questions 4 or 5 in the suicidal ideation section or “yes” to 
any question in the suicidal behavior section of the C-SSRS should not receive any further 


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ubrogepant, must be withdrawn from the study, and should receive appropriate follow-up as 
in routine clinical practice, including the Safety Follow-up visit (Visit 16) if ubrogepant was 
taken.
A patient with a condition and/or a situation that, in the investigator's opinion, may put the 
patient at significant risk, may confound the study results, or may interfere significantly with 
the patient's participation in the study may be withdrawn from treatment.
8.10
Study Termination
Allergan may stop the study (and/or the study site) for any reason with appropriate 
notification.
9.
Adverse Events
AEs occurring during the study will be recorded on an AE eCRF. If AEs occur, the first 
concern will be the safety of the study participants.
9.1
Definitions
9.1.1
Adverse Event
An AE is any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product and that does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product. In addition, during the screening period, AEs will be assessed 
regardless of the administration of a pharmaceutical product.
Note:  AEs must be collected once informed consent has been obtained, regardless of 
whether or not the patient has been administered study drug.
Progression of treatment indication including new or worsening of anticipated clinical signs 
or symptoms, which are collected as clinical efficacy variables and assessed as unequivocally 
associated with the disease progression and/or lack of efficacy, should NOT be reported as 
AEs unless the disease progression is greater than anticipated in the natural course of the 
disease.


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AEs will be assessed, documented, and recorded in the eCRF throughout the study (ie, after 
informed consent has been obtained). At each visit, the investigator will begin by querying 
for AEs by asking each patient a general, non-directed question such as “How have you been 
feeling since the last visit?” Directed questioning and examination will then be done as 
appropriate. All reported AEs will be documented on the appropriate case report form.
9.1.2
Serious Adverse Event
An SAE is any AE occurring at any dose that results in any of the following outcomes: death, 
a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important 
medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered an SAE when, based upon appropriate medical judgment, they may 
jeopardize the patient, or the patient may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. See Section 9.3 for procedures for reporting an 
SAE.
Allergan considers all cancer AEs as SAEs. In addition, Allergan considers any abortion 
(spontaneous or nonspontaneous) as an SAE.
Preplanned surgeries or procedures for pre-existing, known medical conditions for which a 
patient requires hospitalization are not reportable as SAEs.
Any preplanned surgery or procedure should be clearly documented in the site source 
documents by the medically qualified investigator at the time of the patient’s entry into the 
study. If it has not been documented at the time of the patient’s entry into the study, then it 
should be documented as an SAE and reported to Allergan.
9.1.3
Severity
A clinical determination will be made of the intensity of an AE. The severity assessment for 
a clinical AE must be completed using the following definitions as guidelines:
Mild
Awareness of sign or symptom, but easily tolerated
Moderate
Discomfort enough to cause interference with usual activity
Severe
Incapacitating with inability to work or do usual activity


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9.1.4
Relationship to Study Drug or Study Procedure
A determination will be made of the relationship (if any) between an AE and the study drug 
or study procedure, as applicable. A causal relationship is present if a determination is made 
that there is a reasonable possibility that the AE may have been caused by the drug or study 
procedure.
9.2
Procedures for Reporting Adverse Events
Any AE must be recorded on the appropriate eCRF.
All SAEs that are drug-related and unexpected (not listed as treatment-related in the current 
Investigator's Brochure) must be reported to the governing Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) as required by the IRB/IEC, local 
regulations, and the governing health authorities. Any AE that is marked “ongoing” at the 
exit visit must be followed-up as appropriate.
9.3
Procedures for Reporting a Serious Adverse Event
Any SAE occurring during the study period (beginning with informed consent) and for at 
least 30 days after the last dose of study drug must be immediately reported no later than 
24 hours after learning of an SAE. SAEs must be reported to Allergan or Agent of Allergan 
(eg, contract research organization [CRO]) and recorded on the SAE form. All patients with 
an SAE must be followed up and the outcomes reported. The investigator must supply 
Allergan and the IRB/IEC with any additional requested information (eg, autopsy reports and 
discharge summaries).
In the event of an SAE, the investigator must:
1. Notify Allergan immediately by fax or email using the SAE form (contact details can 
be found on page 1 of the SAE form); the fax number is on the front page of this 
protocol, and phone numbers and relevant Allergan personnel contacts are also on the 
study contacts page.
2. Obtain and maintain in his/her files all pertinent medical records, information, and 
medical judgments from colleagues who assisted in the treatment and follow-up of 
the patient.
3. Provide Allergan with a complete, written description of the AE(s) on the SAE form 
describing the event chronologically, including any treatment given (eg, medications 
administered, procedures performed) for the AE(s). Summarize relevant clinical 
information about the event: signs, symptoms, diagnosis, clinical course and relevant 


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clinical laboratory tests, etc. Include any additional or alternative explanation(s) for 
the causality which includes a statement as to whether the event was or was not 
related to the use of the investigational drug.
4. Promptly inform the governing IRB/IEC of the SAE as required by the IRB/IEC, 
local regulations, and the governing health authorities.
9.4
Exposure to Investigational Product During Pregnancy
Study center personnel must report every pregnancy (from the time the patient signs the ICF 
for the trial until 30 days after the last dose of ubrogepant), on the Pregnancy Form as soon 
as possible (within 24 hours of learning of the pregnancy) to the SAE/pregnancy fax number, 
 even if no AE has occurred. Pregnancies in female partners of male 
patients must also be reported. The pregnancy must be followed to term, and the outcome 
reported by completing a follow-up Pregnancy Form. If, however, the pregnancy is 
associated with an SAE (eg, if the mother is hospitalized for hemorrhage), in addition to the 
Pregnancy Form, a separate SAE Form must be filed as described in Section 9.3 with the 
appropriate serious criterion (eg, hospitalization) indicated.
9.5
ALT or AST Elevations
A post-treatment event of ALT or AST ≥ 3 times the ULN is considered an Event of Clinical
Interest. Any patient with this laboratory result after ubrogepant was taken should have 
repeat testing within 48 to 72 hours to confirm the abnormality. For this repeat testing, the 
following tests should be performed: hematology and chemistry panels, international 
normalized ratio (INR), and a toxicology screen for acetaminophen. In addition, the 
investigator should perform a complete history and examination to evaluate for possible liver 
disease. 
All ALT or AST elevations ≥ 3 times the ULN must be reported to Allergan using the AE of 
Interest Form and submitted within 24 hours of the time the investigator becomes aware of 
the event. All new elements of history, physical examination, diagnostic testing results, and 
other relevant medical reports are to be reported for each event.
If an ALT or AST elevation ≥ 3 times the ULN is confirmed and the patient meets any 
of the following criteria, close medical follow-up is required:

Patients with ALT or AST ≥ 3 times ULN and ≤ 5 times the ULN and who are 
asymptomatic with regard to possible liver disease (ie, no fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, or eosinophilia [> 5%])


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
Patients with ALT or AST ≥ 3 times ULN and ≤ 5 times the ULN and (total bilirubin 
< 2 times the ULN and INR < 1.5)
Patients who meet these criteria should be followed clinically, and further medical evaluation 
should be performed per the judgment of the investigator and in conjunction with medical 
personnel at Allergan. The chemistry panel should be repeated 1 to 2 times per week to 
follow the course of ALT/AST elevation. An extra blood sample should be collected and sent 
to the central laboratory for further diagnostic testing at a later date if needed.
If an ALT or AST elevation ≥ 3 times the ULN is confirmed and the patient meets any 
of the following criteria, close medical follow-up is required:

ALT or AST ≥ 3 times the ULN and the patient is symptomatic with the appearance 
of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or 
eosinophilia (> 5%)

ALT or AST ≥ 3 times the ULN and total bilirubin > 2 times the ULN or INR > 1.5

ALT or AST ≥ 5 times the ULN
In addition, for these patients, possible etiologies for acute hepatic injury should be excluded. 
The following laboratory tests should be performed:  anti-hepatitis A IgM, hepatitis B surface 
antigen, anti-hepatitis B core IgM, hepatitis C antibody, hepatitis C quantitative RNA by 
polymerase chain reaction (PCR), anti-hepatitis E IgM. An extra blood sample should be 
collected and sent to the central laboratory for further diagnostic testing at a later date if 
needed. The patient should be followed clinically, and further medical evaluation should be 
done per the judgment of the investigator and in conjunction with medical personnel at 
Allergan. In general, the chemistry panel should be repeated 1 to 2 times per week to follow 
the course of ALT/AST elevation. For procedural details on the medical evaluation of liver 
disease, please see the Study Reference Manual.
The investigator should contact the Allergan Medical Monitor to discuss all cases of 
confirmed ALT/AST elevation ≥ 3 times the ULN. All ALT/AST elevations should be 
followed until ALT and AST return to < 1.5 times the ULN and there is full clinical 
resolution.
Study drug should be discontinued if any of the following criteria are met: 

ALT or AST ≥ 3 times the ULN and the patient is symptomatic with the appearance 
of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or 
eosinophilia (> 5%)

ALT or AST ≥ 3 times the ULN and total bilirubin > 2 times the ULN or INR > 1.5


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
ALT or AST ≥ 5 times the ULN for more than 2 weeks

ALT or AST ≥ 8 times the ULN
The patient may be rechallenged with ubrogepant upon consultation with the Allergan 
Medical Monitor. If a patient is not rechallenged with IP, the patient must be discontinued 
from the study and complete the ET Visit 15 and Safety Follow-Up Visit 16. Patients should 
receive appropriate follow-up as per standard of care.
9.6
Potential Hy’s Law Cases
Sites must report every patient who meets the following potential Hy’s law criteria if this 
occurs within the time the patient signs the ICF until 30 days after the last dose of 
ubrogepant:

ALT or AST ≥ 3 times the ULN, AND

Total bilirubin ≥ 2 times the ULN, AND

Alkaline phosphatase < 2 times the ULN
A laboratory alert for potential Hy’s laws cases will be in place, and the investigators and 
Allergan will be notified immediately when the above criteria have been met. Any potential 
Hy’s law case should be considered an SAE and also reported as an AE of Special Interest. 
Both the SAE and AE of Interest Forms must be completed as soon as possible (within 
24 hours of learning of the potential Hy’s law) and faxed to the SAE/Pregnancy fax number 
. The eCRF pages associated with potential Hy’s law cases should be 
completed within 7 calendar days. Every effort to determine the cause of the liver 
abnormalities must be made, and close monitoring should be initiated in conjunction with the 
Allergan Medical Monitor and in accordance with the FDA “Guidance for Industry: Drug 
Induced Liver Injury - Pre-Marketing Clinical Evaluation,” dated July 2009 (FDA Guidance 
UCM174090, 2009). For specific instructions, please refer to the Study Reference Manual.
9.7
Procedures for Unmasking of Investigational Product
When necessary for the safety and proper treatment of the patient, the investigator can 
unmask the patient’s treatment assignment to determine which treatment has been assigned 
and institute appropriate follow-up care. When possible, the Allergan Medical Monitor 
should be notified prior to unmasking ubrogepant. The investigator should inform the 
Allergan Medical Monitor of the unmasking if there is no notification prior to the unmasking.


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The treatment assignment for the patient can be determined by designated site personnel 
logging into the IWRS via password protected access. The reason for breaking the code must 
be recorded in the patient’s source documents.
10.
Administrative Items
This protocol is to be conducted in accordance with the applicable Good Clinical Practice 
(GCP) regulations and guidelines, eg, the International Conference on Harmonisation (ICH) 
Guideline on GCP.
10.1
Protection of Human Patients
10.1.1
Compliance with Informed Consent Regulations (US 21 CFR 
Part 50) and Relevant Country Regulations
Written informed consent is to be obtained from each patient prior to any study-related 
activities or procedures in the study, and/or from the patient's legally authorized 
representative. 
10.1.2
Compliance with IRB or IEC Regulations
This study is to be conducted in accordance with IRB regulations (US 21 CFR Part 56.103) 
or applicable IEC regulations. The investigator must obtain approval from a properly 
constituted IRB/IEC prior to initiating the study and re-approval or review at least annually. 
Allergan is to be notified immediately if the responsible IRB/IEC has been disqualified or if 
proceedings leading to disqualification have begun. Copies of all IRB/IEC correspondence 
with the investigator should be provided to Allergan.
10.1.3
Compliance with Good Clinical Practice
This protocol is to be conducted in accordance with the applicable GCP regulations and 
guidelines.
10.1.4
Compliance with Electronic Records; Electronic Signatures 
10.1.4.1
Regulations (US 21CFR Part 11)
This study is to be conducted in compliance with the regulations on electronic records and 
electronic signature.


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10.2
Changes to the Protocol
The investigator must not implement any deviation from or changes to the protocol without 
approval by Allergan and prior review and documented approval/favorable opinion from the 
IRB/IEC of a protocol amendment, except where necessary to eliminate immediate hazards 
to study patients, or when the changes involve only logistical or administrative aspects of the 
study (eg, change in monitors, change of telephone numbers).
10.3
Patient Confidentiality
A report of the results of this study may be published or sent to the appropriate health 
authorities in any country in which the study drug may ultimately be marketed, but the 
patients’ names will not be disclosed in these documents. The patients’ names may be 
disclosed to the sponsor of the study, Allergan, or the governing health authorities or the 
FDA if they inspect the study records. Appropriate precautions will be taken to maintain 
confidentiality of medical records and personal information.
10.3.1
Patient Privacy
Written authorization and other documentation in accordance with the local privacy 
requirements (where applicable) is to be obtained from each patient prior to enrollment into 
the study, and/or from the patient's legally authorized representative in accordance with the 
applicable privacy requirements (eg, the Health Insurance Portability and Accountability Act 
Standards for Privacy of Individually Identifiable Health Information [HIPAA]).
In accordance with HIPAA requirements, additional purposes of this study may include 
publishing of anonymous patient data from the study.
10.4
Documentation
10.4.1
Source Documents
Source documents may include a patient's medical records, hospital charts, clinic charts, the 
investigator's patient study files, the eDiary, as well as the results of diagnostic tests, such as 
laboratory tests and electrocardiograms. The investigator's copy of the eCRF serves as part of 
the investigator's record of a patient's study-related data.
The following information should be entered into the patient's medical record:

Patient’s name


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
Patient’s contact information

The date that the patient entered the study, patient number, and patient randomization 
(or medication kit) number

The study title and/or the protocol number of the study and the name of Allergan

A statement that informed consent was obtained (including the date); a statement that 
written authorization or other local patient privacy required documentation for this 
study has been obtained (including the date)

Dates of all patient visits

All concurrent medications (list all prescription and nonprescription medications 
being taken at the time of enrollment; at each subsequent visit, changes to the list of 
medications should be recorded)

Occurrence and status of any AEs

The date the patient exited the study, and a notation as to whether the patient 
completed the study or reason for discontinuation

The results of laboratory tests performed by the site (eg, results of urine pregnancy 
tests)

Key study variables
Source documentation practices must follow Section 4.0 of ICH E6, Good Clinical Practice: 
Consolidated Guidance and ALCOA, ie, records must be attributable, legible, 
contemporaneous, original, and accurate.
10.4.2
Case Report Form Completion
The investigator is responsible for ensuring that data are properly recorded on each patient's 
case report forms and related documents. An investigator who has signed the protocol 
signature page should personally sign for the case report forms (as indicated in the case 
report forms) to ensure that the observations and findings are recorded on the case report 
forms correctly and completely. The case report forms are to be submitted to Allergan in a 
timely manner at the completion of the study, or as otherwise specified by Allergan and will 
be maintained in a central data repository.


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10.4.3
Study Summary
An investigator's summary will be provided to Allergan within a short time after the 
completion of the study, or as designated by Allergan. A summary is also to be provided to 
the responsible IRB/IEC.
10.4.4
Retention of Documentation
All study related correspondence, patient records, consent forms, patient privacy 
documentation, records of the distribution and use of all IPs, and copies of case report forms 
should be maintained on file.
For countries falling within the scope of the ICH guidelines, Allergan-specific essential 
documents should be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IP. These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirement(s) or if needed 
by the sponsor.
In addition, for countries not falling within the scope of the ICH guidelines, local regulatory 
requirements should be followed regarding the retention of clinical study documentation.
Allergan requires that it be notified in writing if the investigator wishes to relinquish 
ownership of the data so that mutually agreed-upon arrangements can be made for transfer of 
ownership to a suitably qualified, responsible person.
10.5
Labeling, Packaging, and Return or Disposal of Investigational 
Products/Treatments
10.5.1
Labeling/Packaging
Ubrogepant will be supplied in blister cards and will be labeled with the protocol number, 
storage information, warning language, and instructions to take the tablets as directed. The 
card will also include the medication number. Immediately before dispensing the blister card, 
the principal investigator or designee will write the study center number, patient’s initials and 
identification number, and date on the card.


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10.5.2
Clinical Supply Inventory
The investigator must keep an accurate accounting of the number of investigational units 
received from Allergan, dispensed or administered to the patients, the number of units 
returned to the investigator by the patient (if applicable), and the number of units returned to 
Allergan during and at the completion of the study. A detailed inventory must be completed 
for all used and unused ubrogepant and packaging. Ubrogepant must be dispensed or 
administered only by an appropriately qualified person to patients in the study. The 
medication is to be used in accordance with the protocol. 
10.5.3
Return or Disposal of Investigational Products/Treatments 
and/or Supplies
All ubrogepant packaging, either empty or containing unused ubrogepant, must be returned 
to the site. All clinical IPs/treatments and/or supplies will be returned to Allergan or Allergan 
designee for destruction.
10.6
Monitoring by Allergan
A representative of Allergan will monitor the study on a periodic basis. The determination of 
the extent and nature of monitoring will be based on considerations such as the objective, 
purpose, design, complexity, blinding, size, and endpoints of the study.
Authorized representatives of Allergan or regulatory authority representatives will conduct 
on-site visits to review, audit and copy study-related documents. These representatives will 
meet with the investigator(s) and appropriate staff at mutually convenient times to discuss 
study-related data and questions.
10.7
Handling of Biological Specimens/Samples
All urine pregnancy testing will be performed on site. Refer to your local laboratory manual 
for handling procedures.
Samples of blood and urine for evaluation of hematology, blood chemistry, and urinalysis 
will be analyzed at a centralized clinical laboratory with certification from a recognized 
accreditation agency (eg, College of American Pathology or Clinical Laboratory 
Improvement Amendments certification).


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10.8
Publications
Allergan, as the sponsor, has proprietary interest in this study. Authorship and manuscript 
composition will reflect joint cooperation between multiple investigators and sites and 
Allergan personnel. Authorship will be established prior to the writing of the manuscript. As 
this study involves multiple centers, no individual publications will be allowed prior to 
completion of the final report of the multicenter study except as agreed with Allergan.
10.9
Coordinating Investigator
A signatory coordinating investigator will be designated prior to the writing of the clinical 
study report.
11.
References
Cady RK, McAllister PJ, Spierings ELH, Messina J, Carothers J, Djupesland PG, et al. A 
randomized, double-blind, placebo-controlled study of breath powered nasal delivery of 
sumatriptan powder (AVP-825) in the treatment of acute migraine (The TARGET Study). 
Headache 2015;55:88–100.
Connor KM, Shapiro RE, Diener HC, Lucas S, Kost J, Fan X, et al. Randomized, 
controlled trial of telcagepant for the acute treatment of migraine. Neurology. 
2009 Sep 22;73(12):970-977.
Food and Drug Administration Guidance for Industry. Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation (UCM174090) July, 2009. 
http://www.fda.gov/downloads/Drugs/.../Guidances/UCM174090.pdf
Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies 
characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann 
Neurol. 1993;33(1):48–56.
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. 
Implications of recent clinical trials for the National Cholesterol Education Program Adult 
Treatment Panel III Guidelines. J Am Coll of Cardiology. 2004;44:720–732.
Hartmaier SL, Santanello NC, Epstein RS, Silberstein SD. Development of a brief 24-hour 
migraine - specific quality of life questionnaire. Headache. 1995;35:320–329.


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Hu XH, Markson LE, Lipton RB, Stewart WF, Berger ML. Burden of migraine in the United 
States. Arch Intern Med. 1999;159:813–818.
Headache Classification Committee of the International Headache Society (IHS). 
The International Classification of Headache Disorders, 3rd edition (beta version). 
Cephalalgia. 2013;33(9):629–808. http://www.ihs-
classification.org/_downloads/mixed/InternationalHeadache-Classification-III-ICHD-III-
2013-Beta.pdf.
Katsarava Z, Buse DC, Manack AN, Lipton RB. Defining the differences between episodic 
migraine and chronic migraine. Curr Pain Headache Rep. 2012;16(1):86–92.
Lipton RB, Bigal ME, Diamond M, Freitag F, Reed MI, Stewart WF, on behalf of the AMPP 
advisory group. Migraine prevalence, disease burden, and the need for preventive therapy. 
Neurol. 2007;68(5):343–349.
National Cholesterol Education Program Adult Treatment Panel III Guidelines. NIH 
Publication No. 01-3670, May 2001. http://www.scymed.com/en/smnxdj/edzr/edzr9610.htm. 
Olesen J, Diener H-C, Husstedt IW, Goadsby PJ, Hall D, Meier U, et al. Calcitonin 
gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. 
N Engl J Med. 2004;350(11):1104–1110.
Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ, et al. Headache 
Classification Committee. New appendix criteria open for a broader concept of chronic 
migraine. Cephalalgia. 2006;26(6):742–746.
Santanello NC, Hartmaier SL, Epstein RS, Silberstein SD. Validation of a new quality of life 
questionnaire for acute migraine headache. Headache.1995;35:330–337.
Stovner LJ, Andree C. Prevalence of headache in Europe:  a review for the Eurolight Project. 
J Headache Pain. 2010;11:289–299.
Tepper SJ, Cady RK, Silberstein S, Messina J, Mahmoud RA, Djupesland PG, et al. AVP 
825 breath-powered intranasal delivery system containing 22 mg sumatriptan powder vs 
100 mg oral sumatriptan in the acute treatment of migraines (The COMPASS study): a 
comparative randomized clinical trial across multiple attacks. Headache. 
2015;55(5):621-635.


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12.
Attachments
12.1
Examination Procedures, Tests, Equipment, and Techniques
12.1.1
International Classification of Headache Disorders, 3rd Edition, 
Beta Version


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12.2
Examples of Prohibited Medications
Prohibited Medications
The following medications are prohibited 30 days prior to Screening and throughout the 
study period for patients taking ubrogepant. Note that for patients assigned to the usual-care
arm, these restrictions do not apply.
Strong/Moderate CYP3A4 Inducers
Strong/Moderate CYP3A4 Inhibitors
Antidepressant/ 
Antianxiety
Barbiturates 
•
Amobarbital (Amytal®)
•
Aprobarbital (Alurate®)
•
Butalbital (Fiorinal®, 
Fioricet®)
•
Butabarbital (Busodium®, 
Butisol®)
•
Mephobarbital (Mebaral®)
•
Pentobarbital (Nembutal®)
•
Phenobarbital (Luminal®, 
Solfoton®)
•
Secobarbital (Seconal®)
Nefazodone (Serzone®)
Antiseizure
Carbamazepine (Atretol®, Carbatrol®, 
Epitol®, Equetro®, Tegretol®)
Oxcarbazepine (Trileptal®) 
Phenytoin (Dilantin®, Phenytek®)
Primidone (Myidone®, Mysoline®)
Diabetes
Pioglitazone (Actos®)
Troglitazone (Rezulin®, Resulin®)
Antiemetic
Aprepitant (Emend®)
Antihypertension
Diltiazem (Cardizem®)
Verapamil (Calan®, Calan SR®)
Glucocorticoid 
(Systemic)
Betamethasone (Celestone®)
Dexamethasone (Baycadron®, 
DexPak®)
Hydrocortisone (Cortef®)
Methylprednisolone (Medrol®)
Prednisolone (Prelone®)
Prednisone (Deltasone®)
Triamcinolone (Kenalog®)
Antibiotics
Rifabutin (Mycobutin®) 
Rifampicin/Rifampin (Rifadin®, 
Rifater®, Rimactane®) 
Erythromycin ( Benzamycin®,
EryTab®)
Clarithromycin (Biaxin®)
Telithromycin (Ketek®)
Antifungal
Fluconazole (Diflucan®, Trican®)
Itraconazole (Sporanox®)
Ketoconazole (Nizoral®)


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Strong/Moderate CYP3A4 Inducers
Strong/Moderate CYP3A4 Inhibitors
Anti-HIV
Efavirenz (Stocrin®, Sustiva®) 
Nevirapine (Viramune®)
Indinavir (Crixivan®)
Nelfinavir (Viracept®) 
Ritonavir (Norvir®)
Saquinavir (Fortovase®, Invirase®)
Immunosuppressant
Cyclosporine - oral/intravenous only 
(Neoral®, Sandimmune®)
Other
St John’s wort
Enzalutamide (Xtandi®)
Modafinil (Provigil®)
Buprenorphine (Cizol®, Subutex®, 
Suboxone®)
Quinine, armodafinil (Nuvigil TM)
Drugs with Narrow Therapeutic Margins
Warfarin (Coumadin®)
Digoxin (Digitek®, Lanoxin®, Digox®)
Cisapride (Prepulsid®, Propulsid®) 
Pimozide (Orap®)
The following medications are allowed during the study; however, they are prohibited within 
48 hours prior to taking ubrogepant:
Triptan
Almotriptan (Axert®)
Eletriptan (Relpax®)
Frovatriptan (Frova®)
Naratriptan (Amerge®)
Rizatriptan (Maxalt®) 
Sumatriptan (Imitrex®) 
Zolmitriptan (Zomig®)
Ergot Derivative
Dihydroergotamine (DHE 45®, Migranal®)
Ergotamine (Cafergot®, Ergomar®, Wigraine®)
Opioid
Tramadol (eg, Ultracet®, Ultram®)
Butorphanol (Stadol®)
Codeine-containing analgesics (eg, Tylenol with Codeine #3®)
Hydrocodone (Zohydro ER™)/Hydrocodone-containing analgesics 
(eg, Vicodin®)
Oxycodone (Oxycontin®, Roxicodone®)/Oxycodone-
containing analgesics (eg, Percocet®) 
Morphine (MS Contin®)
NSAID
Aspirin 
Combination medicines with NSAIDS (eg, Excedrin®)
Diclofenac (Arthrotec®, Cataflam®, Voltaren®)
Ibuprofen (eg, Advil®, Excedrin IB®, Motrin®)
Ketoprofen (eg, Orudis®) 
Naproxen (eg, Aleve®, Naprosyn®)
Analgesic
Acetaminophen (eg, Tylenol® or any combination drug Tylenol®)


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Antiemetic agent
Chlorpromazine (Thorazine®)
Hydroxyzine (Vistaril®)
Metoclopramide (Reglan®)
Ondansetron (Zofran®)
Prochlorperazine (Compazine®)
Promethazine (Phenergan®, Mepergan®)
Proton Pump Inhibitor
Esomeprazole (Nexium®)
Lansoprazole (Prevacid®, Zoton®)
Omeprazole (Losec®, Prilosec®, Zegerid®)
Pantoprazole (Pantoloc®, Pantozol®, Protonix®, Somac®, Zurcal®) 
Rabeprazole (Aciphex®, Pariet®, Rabecid®)
The following medications are allowed during the study; however, they are prohibited within 
24 hours prior to taking ubrogepant:
Antacid
Aluminum Carbonate Gel (Basaljel®)
Aluminum Hydroxide (AlternaGEL®, Amphojel®)
Aluminum Hydroxide and magnesium hydroxide (Maalox®, Mylanta®)
Bismuth Subsalicylate (Pepto-bismol®)
Calcium Carbonate (Alcalak®, Quick-Eze®, Rennie®, Rolaids®, Titralac®, 
TUMS®)
Hydrotalcite (Talcid®)
Magaldrate plus Simethicone (Pepsil®)
Magnesium Hydroxide (Phillips' Milk of Magnesia®)
Sodium Bicarbonate (Alka-Seltzer®, Bicarbonate of Soda®)
H2 Blocker
Famotidine (Pepcid®)
Nizatidine (Axid®)
Ranitidine (Zantac®)
Cimetidine (Tagamet®)


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12.3
Glossary of Abbreviations
Term/Abbreviation
Definition
AE
adverse event
ALCOA
attributable, legible, contemporaneous, original, and accurate
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BCRP
breast cancer resistance protein
CGRP
calcitonin gene-related peptide
CGRP RA
CGRP receptor antagonist
CHD
coronary heart disease
CRO
contract research organization
C-SSRS
Columbia-Suicide Severity Rating Scale
CV
cardiovascular
CYP
cytochrome P450
CYP3A4
cytochrome P450 3A4
ECG
electrocardiogram
eCRF
electronic case report form
eDISH
evaluation of drug-induced serious hepatotoxicity
ET
early termination
GCP
Good Clinical Practices
HEOR
Health Economics and Outcomes Research
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Conference on Harmonization
ICHD-3 beta
International Classification of Headache Disorders criteria, 3rd 
edition beta version
IEC
Independent Ethics Committee
INR
international normalized ratio (blood-clotting test)
IP
investigational product


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IRB
Institutional Review Board
IV
intravenous
IWRS
interactive web response system
LOCF
last observation carried forward
mITT
modified intent-to-treat
NCEP
National Cholesterol Education Program
NSAID
nonsteroidal anti-inflammatory drug
PCS
potentially clinically significant
PCR
polymerase chain reaction
PF
pain freedom
PR
pain relief
PR interval
the period from the beginning of the P wave (the onset of atrial 
depolarization) until the beginning of the QRS complex (the onset of 
ventricular depolarization)
QoL
Quality-of-Life
QRS interval
part of ECG corresponding to the depolarization of the right and left 
ventricles of the human heart.
QT interval
time between the start of the Q wave and the end of the T wave in the 
heart's electrical cycle. The QT interval represents electrical 
depolarization and repolarization of the ventricles.
QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate using the Fridericia formula 
(QTcF = QT/(RR)⅓)
RR interval
interval between R waves in ECG
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SNRI
serotonin norepinephrine reuptake inhibitors
SPF
sustained pain freedom
SSRI
selective serotonin reuptake inhibitors
TBL
total bilirubin
TEAE
treatment-emergent adverse event
ULN
upper limit of normal


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US
United States
WOCBP
women of childbearing potential


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12.4
Protocol Amendment 1 Summary
Title:  A Multicenter, Randomized, Open-label Extension Study to Evaluate the Long-term 
Safety and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine With or 
Without Aura
Protocol UBR-MD-04 Amendment 1
Date of Amendment:  15 Nov 2016
Amendment Summary
This summary includes changes made to Protocol UBR-MD-04 (02 May 2016). This 
protocol was amended to:  1) update health outcomes measures and efficacy variables; and 
2) clarify Exclusion Criterion 2. Following is a summary of content-oriented changes that 
were made to each section of the protocol, and a brief rationale for these changes. Minor 
editorial and document formatting revisions have not been summarized.
Section
Revision
Rationale
Global Change
In reference to the Satisfaction With Study 
Medication assessment, instances of 
“migraine treatment” were changed to “study 
medication”
Based on input from patient 
qualitative interviews, expert 
panel suggested rephrasing 
“migraine treatment” to “study 
medication”
Global Change
Revised SAE/Pregnancy Reporting Fax 
Number
Administrative update
Global Change
 
 
Global Change
 
 
 
 
Protocol Title Page
Revised name of the Authorized US Agent 
from Allergan, Inc. to Allergan Sales, LLC
Administrative update
 
Administrative update


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Section
Revision
Rationale
Protocol Summary –
General Statistical 
Methods and Types of 
Analyses
 
 
 
 
 
 
 
 
 
 
 
 
, 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 3.1, Section 
Title
Section title and in-text change updated to 
“Data Drug Safety Monitoring Board” 
Clarification


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Section
Revision
Rationale
Section 4.4,
 
 
 
 
 
 
 
 
 
 
Clarification
Section 4.5.1, 
Permissible 
Medications/Treatments
Added text regarding prohibited and allowed 
medications for those assigned to the 
usual-care arm:
Medications that are not specifically 
prohibited are allowed, with the following 
clarifications and restrictions for patients 
taking ubrogepant. Note that for patients 
assigned to the usual-care arm, these 
restrictions do not apply.
Clarification to note that 
restrictions on medications do 
not apply to patients in the 
usual-care arm
Deleted “any proton pump inhibitor” from
list of medications  prohibited within 24
hours prior to taking IP and added it to list of 
medications prohibited within 48 hours prior 
to IP dosing
Amended per FDA request
Section 4.5.1.2,
Definition of Females of 
Childbearing Potential 
and/or Acceptable 
Contraceptive Methods
Moved surgical sterilization from a method 
of contraception to defining WOCBP:
For the purposes of this study, females will 
be considered of childbearing potential 
unless they are naturally postmenopausal (ie, 
no menses for 2 years) or permanently 
sterilized (ie, bilateral tubal ligation, bilateral 
salpingectomy, bilateral oophorectomy or
hysterectomy).
Clarification


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Section
Revision
Rationale
Section 4.5.1.2,
Definition of Females of 
Childbearing Potential 
and/or Acceptable 
Contraceptive Methods
Updated acceptable contraceptive methods:
For WOCBP who may participate in the 
study, the following methods of 
contraception, if properly used, are generally 
considered reliable: hormonal contraceptives 
(ie, oral, patch, vaginal ring, injection, 
implant), male condom with intravaginal 
spermicide, diaphragm or cervical cap with 
spermicide, vaginal contraceptive ring, 
intrauterine device, surgical sterilization 
(bilateral tubal ligation, bilateral 
salpingectomy), vasectomized partner, or 
sexual abstinence….. Male participants must 
also refrain from donating sperm during the 
course of the study.
Clarification
Section 4.5.2,
Prohibited 
Medications/Treatments
Added text regarding prohibited medication: 
The following medications are prohibited 
throughout the study period for patients 
taking ubrogepant. Note that for patients 
assigned to the usual-care arm, these 
restrictions do not apply.
Clarification to note that 
restrictions on medications do 
not apply to patients in the 
usual-care arm
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Section
Revision
Rationale
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 6.3,
Other Study Supplies
Deleted Allergan-supplied thermometer from 
list of Allergan-provided supplies:

ElPro Libero thermometer
Clarification to note that 
Allergan will not provide a 
thermometer
 
 
 
 
 
 


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Section
Revision
Rationale
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 8.8,
Early Discontinuation of 
Patients
Revised text regarding prematurely 
discontinued patients: 
A final assessment will be defined as 
completion of the evaluations scheduled for 
Visit 15/ET. If the patient discontinues 
prematurely after ubrogepant is taken,, the 
patient is expected to return for a safety 
follow-up visit 4 weeks postdose after 
Visit 15/ET.
Clarification to note that all 
patients, independent of 
randomization treatment arm, 
will need to return for a Safety 
Follow-up visit
Section 9.5,
ALT or AST Elevations
Revised re-challenge text: If a patient is not 
rechallenged with IP, the patient must  be 
discontinued from the study and complete the 
Early Termination Visit 15 and Safety 
Follow-Up Visit 16. Patients should receive 
appropriate follow-up as per standard of care.
Clarification regarding follow-up 
if the patient is not rechallenged 
with IP
Section 11, References
Added Cady and Tepper references
Administrative update


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Section
Revision
Rationale
Section 12.2,
Examples of Prohibited 
Medications
Revised introductory text: 
The following medications are prohibited 
30 days prior to Screening and throughout 
the study period for patients taking 
ubrogepant. Note that for patients assigned to 
the usual-care arm, these restrictions do not 
apply.
Clarification to note that 
restrictions on medications do 
not apply to patients in the 
usual-care arm.
Deleted the following Proton Pump 
Inhibitors from the list of medications 
prohibited within 24 hours prior to IP dosing
and added them to the list of medications 
prohibited within 48 hours prior to IP dosing:
Esomeprazole (Nexium®)
Lansoprazole (Prevacid®, Zoton®)
Omeprazole (Losec®, Prilosec®, Zegerid®)
Pantoprazole (Pantoloc®, Pantozol®, 
Protonix®, Somac®, Zurcal®)
Rabeprazole (Aciphex®, Pariet®, Rabecid®)
Amended per FDA request
Added to “Others” category: armodafinil 
(NuvigilTM)
Clarification
Section 12.3,
Glossary of 
Abbreviations
 
 


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12.5
Protocol Amendment 2 Summary
Title:  A Multicenter, Randomized, Open-label Extension Study to Evaluate the Long-term 
Safety and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine With or 
Without Aura
Protocol UBR-MD-04 Amendment 2
Date of Amendment:  06 Dec 2017
Amendment Summary
This summary includes changes made to Protocol UBR-MD-04 (02 May 2016) and Protocol 
Amendment 1 (15 Nov 2016). This protocol was amended to: 1) add a new health outcomes 
measure and update variables; 2) update the definition of the safety population. Following is 
a summary of content-oriented changes that were made to each section of the protocol, and a 
brief rationale for these changes. Minor editorial and document formatting revisions have not 
been summarized.
Section
Revision
Rationale
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
Clarification


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Section 7.1.2 Safety 
Population 
Definition changed as follows:
The Safety population will will be defined 
separately for the ubrogepant arms and the 
usual-care arm. 
Ubrogepant arms: All randomized patients who 
received ≥ 1 dose of treatment 
Usual care arm: All randomized patients in the 
usual-care arm. 
The purpose of the usual care arm is to
Definition of Safety population 
modified to include all 
randomized patients in the 
usual-care arm to better 
contextualize the safety 
findings for both arms.


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contextualize any safety findings that may occur 
in the ubrogepant treated patients over the 
course of 12 months.  As such, data from all 
patients randomized to the usual care arm, 
regardless of whether the patient used 
medication to treat migraine, will be included in 
the safety analyses.
 
 
 
 
 
 
 
 
 
 
Section 7.3.2.1 Adverse 
Events
Defined first dose of treatment in the lead-in 
study throughout section
Clarification
AE redefined:
An AE that occurs after Visit 16 for patients 
with Visit 16 or more than 30 days after the last 
dose of treatment visit for patients without Visit 
16 will not be considered as a TEAE.
Clarification
The number and percentage of patients 
reporting TEAEs after randomization in each 
treatment group will be tabulated by descending 
percentage in any group, by system organ class 
and preferred term, and further categorized by 
severity and causal relationship to the study 
treatment. 
Clarification
An SAE that occurred between the date of the 
first dose of treatment in the lead-in study and 
Visit 16 for patients with Visit 16 or within 30 
days after the last dose of treatment visit for 
patients without Visit 16, inclusive, will be 
considered an on-therapy SAE. The number and 
percentage of patients who have on-therapy 
SAEs after the first dose of treatment
randomization will be summarized by preferred 
term and treatment group. In addition, the 
incidence of on-therapy SAEs that led to death 
will be summarized separately by preferred 
term for each treatment group. 
Clarification
Section 7.3.2.3 Clinical 
Laboratory Parameters
Text clarified as follows:
Any post-treatment ALT and/or AST results 
that are ≥ 3 times the ULN are considered 
events of clinical interest in this study and are 
patient subject to blinded adjudication by the 
Clinical Adjudication Committee to determine 
whether the elevation is due to treatment or not, 
Typo


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and to determine whether there is a confounding 
factor. 
Section 7.3.2.4 Vital Signs 
Measurements
Added BMI:
Descriptive statistics for vital sign 
measurements (sitting and standing systolic and 
diastolic BP, sitting and standing pulse rate, 
respiratory rate, temperature, and weight, and 
BMI) and changes from baseline values at each 
visit and at the end of study will be presented by 
treatment group. 
Administrative change
7.3.2.6
Suicidality 
Assessment
Timing of assessment amended as follows:
For the C-SSRS, the number of patients with 
suicidal ideation and suicidal behavior in 
lifetime history, during the treatment period, 
and during the safety follow-up period after the 
first dose of treatment will be summarized by 
treatment group for the Safety population. 
Clarification
Section 7.3.2.7 Potential 
Hy’s Law
Timing of assessment amended as follows:
Patients who meet the potential Hy’s Law 
criteria from the first dose of treatment
randomization to Visit 16 will be summarized. 
Supportive tabular displays also will be 
provided. 
Clarification
 
 
 
 
 
 
 
 
 
Section 9.3 Procedures for 
Reporting a Serious 
Adverse Event
Notify Allergan immediately by fax or email 
using the serious adverse eventSAE form 
(contact details can be found on page 1 of the 
serious adverse event SAE form); the fax 
number is on the front page of this protocol, and
phone numbers and relevant Allergan personnel 
contacts are also on the frontstudy contacts page 
of protocol.
Changed to show correct 
location of study contact 
details


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Section 9.5 ALT or AST
Elevations
For this repeat testing, the following tests 
should be performed: hematology and 
chemistry panels, international normalized ratio 
(INR), and a urine toxicology screen for 
acetaminophen. 
The toxicology screen for 
acetaminophen will not be 
tested from urine samples
Section 11 References
 
 
 
Santanello NC, Hartmaier SL, Epstein RS, 
Silberstein SD. Validation of a new quality of 
life questionnaire for acute migraine headache. 
Headache 1995;35:330-337.
O’Brien P. Procedures for comparing samples 
with multiple endpoints. Biometrics 
1984;40:1079-1087.
Reference added to support 
Section 7.3.1 Efficacy 
Analyses
 
12.6
Protocol Amendment 3 Summary
Title:  A Multicenter, Randomized, Open-label Extension Study to Evaluate the Long-term 
Safety and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine With or 
Without Aura
Protocol UBR-MD-04 Amendment 3
Date of Amendment: 11 Apr 2018
Amendment Summary
This summary includes changes made to Protocol UBR-MD-04 (02 May 2016), Protocol 
Amendment 1 (15 Nov 2016), and Protocol Amendment 2 (06 Dec 2017). This protocol 
was amended primarily to add information regarding an interim analysis, update efficacy 
endpoints, and add a subgroup analysis for safety. Following is a summary of 
content-oriented changes that were made to each relevant section of the protocol and a brief 
rationale for each of these changes. If needed to clarify revisions, added text is shown in bold 
italics and deleted text is shown with strikethroughs. Minor editorial and document 
formatting revisions have not been summarized.


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Section
Revision
Rationale
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Summary –
Study Design
The following revision was made in the 
“Structure” section of the protocol summary:
Structure: multicenter, randomized, open-
label, 52-week extension study; 
randomization to the ubrogepant arms (50 
and 100 mg) will be blinded
This information was 
removed to avoid 
redundancy.
Protocol Summary –
General Statistical 
Methods and Types of 
Analyses
Changes made to this section are described 
below.
 
 
 
 
 
 
3.
The safety analyses information was 
revised as follows:
The safety analyses will be performed using 
the Safety population and will include AEs, 
clinical laboratory evaluations, vital sign 
measurements, ECG parameters, and the 
C-SSRS. For each of the clinical, laboratory, 
vital sign, and ECG parameters, the last 
nonmissing safety assessment before the first 
dose of treatment the first dose in the lead-in 
study will be used as the baseline for all 
analyses of that safety parameter. Continuous 
variables will be summarized by the number 
of patients and mean, SD, median, minimum, 
and maximum values. Categorical variables 
 
 
 
 
 
The safety analyses 
information was changed as 
a clarification.


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will be summarized by number and 
percentage of patients.
Protocol Summary –
General Statistical 
Methods and Types of 
Analyses
The following statement was removed from 
this section: “Summary statistics for the 
patient-specific monthly attack rates will be 
provided by treatment groups.”
This information was 
removed because this 
analysis is no longer being 
performed for efficacy but 
will be summarized for the 
Safety Population.
Protocol Summary –
General Statistical 
Methods and Types of 
Analyses
 
 
 
 
 
 
 
 
 
Section 3 – Study 
Design
The following revision was made in this 
section:
This multicenter, randomized, open-label, 
52-week extension study will enroll 
approximately 1200 patients from 
approximately 200 centers in the United 
States. Patients will be randomized (1:1:1) to 
1 of the following 3 treatment groups: usual 
care, ubrogepant 50 mg, or ubrogepant 
100 mg (400 patients per arm). The study is 
open-label; however, randomization to the 
ubrogepant arms (50 and 100 mg) will be 
blinded. If and when an interim analysis 
occurs, the doses will be unblinded (see 
Section 7.6).
The randomization to the 
ubrogepant arms has been 
blinded; however, this 
section was revised because 
after the interim analysis, if 
performed, Allergan will be 
unblinded to the ubrogepant 
doses. Sites and patients 
will remain blinded 
throughout the study. 
Details of the interim 
analysis and blinding are 
provided in Section 7.6.
Section 5.4 –Treatment 
Allocation Ratio and 
Stratification
The following revision was made in this 
section:
Patients will be randomized (1:1:1) to 1 of 
the following 3 treatment groups: usual-care, 
ubrogepant 50 mg, or ubrogepant 100 mg. 
The study is open-label; however, 
randomization to the ubrogepant arms 
(50 and 100 mg) will be blinded. If and 
when an interim analysis occurs, the doses 
will be unblinded (see Section 7.6).
The randomization to the 
ubrogepant arms has been 
blinded; however, this 
section was revised because 
after the interim analysis, if 
performed, Allergan will be 
unblinded to the ubrogepant 
doses. Sites and patients 
will remain blinded 
throughout the study. 
Details of the interim 
analysis and blinding are 
provided in Section 7.6.
 
 
 
 
 
 
 
 
 


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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.3.2 – Safety Analyses
The safety analyses information was revised 
as follows:
The safety analyses will be performed using 
the Safety population. The safety parameters 
will include AEs, clinical laboratory 
evaluations, vital sign measurements, ECG 
parameters, and the C-SSRS. For each of the 
clinical, laboratory, vital sign, and ECG 
parameters, the last nonmissing safety 
assessment before the first dose of treatment
in the lead-in study will be used as the 
baseline for all analyses of that safety 
parameter. 
The safety analyses 
information was revised as a 
clarification.
7.3.2.1 – Adverse Events
The following revision was made regarding 
the definition of a TEAE:
An AE that occurs after Visit 16 for patients 
with Visit 16, or more than 30 days after the 
last visit or last treatment, whichever is 
later, for patients without Visit 16 will not be 
This information was 
revised as a clarification.


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considered as a TEAE.
7.3.2.1 – Adverse Events
The statement regarding tabulation of 
TEAEs was revised as follows:
The number and percentage of patients 
reporting TEAEs after randomization in each 
treatment group will be tabulated by 
descending percentage in any the highest 
dose group, by system organ class and 
preferred term, and further categorized by 
severity and causal relationship to the study 
treatment. 
This information was 
revised as a clarification.
7.3.2.1 – Adverse Events
The following revisions were made 
regarding the definition of an SAE and the 
summarization of deaths:
A SAE that occurred between the date of the 
first dose of treatment in the lead-in study 
and Visit 16 for patients with Visit 16, or 
within 30 days after the last visit or last 
treatment, whichever is later, for patients 
without Visit 16, inclusive, will be 
considered an on-therapy SAE. The number 
and percentage of patients who have 
on-therapy SAEs after randomization will be 
summarized by preferred term and treatment 
group. In addition, the incidence of on-
therapy SAEs that led to death will be
summarized separately by preferred term for 
each treatment group.
The definition of SAE was 
revised as a clarification.
The statement regarding 
summarization of death was 
removed because this 
information will not be 
presented in tabular format.


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7.3.2.1 – Adverse Events
The following revisions were made 
regarding summarization of TEAEs of 
special interest:
The number and percentage of patients 
with TEAEs of clinical interest will be 
summarized by preferred term and 
treatment group. TEAEs of clinical 
interest include triptan-associated TEAEs, 
abuse-related TEAEs, hepatic injury 
TEAEs, cardiac arrhythmias TEAEs, 
central nervous system TEAEs, vascular 
disorders TEAEs, embolic and thrombotic 
events TEAEs, hypertension TEAEs, 
ischemic heart disease TEAEs, and 
suicide/self-injury TEAEs. The number and 
percentage of patients who had triptan-
associated AEs also will be summarized by 
treatment group. The triptan-associated AE 
class consists of the following individual 
AEs: any chest pain, chest tightness, throat 
tightness, asthenia, paresthesia, dysesthesia, 
and hyperesthesia.
The paragraph regarding 
summarizations of TEAEs 
of special interest was 
revised because of a change 
in the way this information 
is being presented.
Section 7.4 – Subgroup 
Analyses
The following revision was made to this 
section:
Subgroup analyses will be done for 
disposition, treatment exposure, and TEAEs 
for sex, age group (< 40 vs ≥40, and < 65 vs 
≥65), race (white vs all other races), 
cardiovascular risk category, and renal 
function class.No subgroup analysis is 
planned for this study.
This information was added 
because subgroup analyses 
are now planned for this 
study.
 
 
 
 
 
 
 
 
 
 
 
Section 7.6 – Interim 
Analysis
This section has been revised to include 
information regarding an interim analysis, as 
follows:
No interim analysis is planned for this study.
The interim analysis for Study UBR-MD-04 
will occur when at least 300 ubrogepant 
patients (with a minimum of 2 migraines 
treated with ubrogepant per month, on 
average) have been enrolled in 
Study UBR-MD-04 for 6 months and 
200 ubrogepant patients (with a minimum 
This new information was 
added because an interim 
analysis is now planned for 
this study if requirements 
are met.


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of 2 migraines treated with ubrogepant per 
month, on average) have been enrolled in 
Study UBR-MD-04 for 1 year. 
In regards to blinding, although this is an 
open-label study, randomization to the 
ubrogepant 50 mg or 100 mg arms is 
blinded. If and when an interim analysis 
occurs, Allergan staff will be unblinded to 
the ubrogepant doses; however, patients 
and sites will remain blinded. The interim 
analysis will include all analyses specified 
in the SAP except for efficacy analyses.
Details regarding the interim analysis are
specified in the SAP.

SAP_001.pdf: 
NCT02873221 
 
 
Study ID: UBR‐MD‐04 
 
 
 
Title: A Multicenter, Randomized, Open‐Label Extension Study to Evaluate the Long‐Term Safety and 
Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine With or Without Aura 
 
 
Statistical Analysis Plan Amd 2 Date: 04‐Sept‐2018 
 
 
 


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1.
Title Page
STATISTICAL ANALYSIS PLAN
A MULTICENTER, RANDOMIZED, OPEN-LABEL EXTENSION STUDY TO EVALUATE 
THE LONG-TERM SAFETY AND TOLERABILITY OF ORAL UBROGEPANT IN THE 
ACUTE TREATMENT OF MIGRAINE WITH OR WITHOUT AURA
Amendment 2: 2018-09-04
Protocol Number:
UBR-MD-04 Amendment 2
Development Phase:
3
Product Name:
Ubrogepant
Study Statistician:
.
Sponsor:
Allergan Pharmaceuticals
2525 Dupont Drive
Irvine, California USA  92612
+1-714-246-4500
+1-800-347-4500
This document is the property of Allergan. and may not—in full or part—be passed on, reproduced, 
published, distributed to any person, or submitted to any regulatory authority without the express written 
permission of Allergan.


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2.
Table of Contents
1.
Title Page ..............................................................................................................................................1
2.
Table of Contents..................................................................................................................................2
2.1
List of Tables..............................................................................................................................3
2.2
List of Figures.............................................................................................................................5
3.
List of Abbreviations and Definition of Terms.....................................................................................6
4.
Introduction...........................................................................................................................................8
4.1
Study Design Summary..............................................................................................................8
4.2
Study Objectives and Endpoints.................................................................................................8
5.
Statistical Methodology and Study Endpoints ....................................................................................13
5.1
Statistical Methods Planned in the Protocol and Determination of Sample Size .....................13
5.1.1
Statistical and Analytical Plans ...................................................................................13
5.1.1.1
Common Conventions.................................................................................13
5.1.1.2
Demographics..............................................................................................18
5.1.1.4
Safety Analyses ...........................................................................................26
5.1.1.5
Subgroup Analyses......................................................................................34
5.1.1.6
Interim Analyses..........................................................................................34
5.2
Changes in the Conduct of the Study or Planned Analyses......................................................35
5.2.1
Changes in the Conduct of the Study ..........................................................................35
5.2.2
Changes to Analyses Prior to Database Lock..............................................................35
6.
Data Handling and Analysis Conventions ..........................................................................................36
6.1
Study Treatment Conventions ..................................................................................................36
6.1.1
Analysis Days..............................................................................................................36
6.1.2
Missing/Incomplete Treatment End Date....................................................................36
6.2
Analysis Visit Windows ...........................................................................................................36
6.2.2
Safety...........................................................................................................................37


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6.3.4.2
AE Group of Interest ...................................................................................40
6.3.5
Clinical Laboratory Assessments ................................................................................41
6.3.5.1
Potentially Clinically Significant Criteria ...................................................41
6.3.5.2
Hepatic Laboratory Abnormalities ..............................................................42
6.3.5.3
Continuous Descriptives and Shift Table Parameters..................................44
6.3.5.4
Character Values..........................................................................................44
6.3.6
Vital Signs ...................................................................................................................44
6.3.6.1
Potentially Clinically Significant Criteria ...................................................44
6.3.6.2
Continuous Descriptives and Shift Table Parameters..................................45
6.3.7
Electrocardiograms......................................................................................................45
6.3.7.1
QTc Derivation............................................................................................45
6.3.7.2
Potentially Clinically Significant Criteria ...................................................45
6.3.7.3
Continuous Descriptives and Shift Table Parameters..................................46
6.4
Imputed Value Listing Conventions.........................................................................................46
7.
Amendment(s).....................................................................................................................................46
8.
Appendices..........................................................................................................................................48
8.1
Appendix I: Preferred Terms for AE Categories of Clinical Interest Created by SMQs..........48
2.1
List of Tables
Table 3-1
Abbreviations and Definitions of Terms.............................................................................6
Table 4-1
Study Objectives and Corresponding Endpoints ................................................................9
Table 5-1
Analysis Populations.........................................................................................................13
Table 5-2
Statistical Methodology ....................................................................................................14
Table 5-3
Missing Data Handling by Endpoint Type .......................................................................15
Table 5-4
Analysis Population Summaries .......................................................................................18
Table 5-5
Participant Disposition Summaries...................................................................................18
Table 5-6 
Classification of Renal Function Based on Estimated GFR (eGFR)................................19
Table 5-7
Protocol Deviation Summary............................................................................................20
Table 5-8
Demographic Summaries..................................................................................................20


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Table 5-9
Baseline Characteristics Summaries.................................................................................20
Table 5-10
Medical History Summary................................................................................................21
Table 5-11
Migraine History Summary ..............................................................................................21
Table 5-12
Medication Summaries .....................................................................................................22
Table 5-16
Safety Endpoint Baseline Definitions...............................................................................26
Table 5-17
Treatment Exposure Summaries.......................................................................................27
Table 5-18
Treatment Compliance Summaries...................................................................................28
Table 5-19
AE Terms..........................................................................................................................28
Table 5-20
AE Summaries..................................................................................................................29
Table 5-21
Clinical Laboratory Summaries........................................................................................31
Table 5-22
Potential Hy's Law Summaries.........................................................................................32
Table 5-23
Vital Signs Summaries......................................................................................................32
Table 5-24
ECG Summaries ...............................................................................................................33
Table 5-25
Cardiovascular Risk Summaries.......................................................................................34
Table 5-26
Suicidality Summaries ......................................................................................................34
Table 6-1
Analysis Day Definitions..................................................................................................36
Table 6-4
Safety Analysis Visit Definitions for 3-Month Time Interval ..........................................37
Table 6-5
Safety Analysis Visit Definitions for 1-Month Time Interval ..........................................37
Table 6-6
Safety Analysis Visit Definitions......................................................................................37
Table 6-10
Construction Methods for AE Categories of Clinical Interest..........................................40


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Table 6-11
Preferred Terms for Abuse-Related Category and Triptan-Associated Category.............41
Table 6-12
Clinical Laboratory PCS Criteria......................................................................................41
Table 6-13
Criteria for Hepatic Laboratory Abnormalities.................................................................43
Table 6-14
Clinical Descriptive and Shift Table Parameters..............................................................44
Table 6-15
Vital Sign PCS Criteria.....................................................................................................44
Table 6-16
Vital Sign Descriptive and Shift Table Parameters ..........................................................45
Table 6-17
QTc Derivation .................................................................................................................45
Table 6-18
ECG PCS Criteria.............................................................................................................46
Table 6-19
ECG Descriptive and Shift Table Parameters...................................................................46
Table 8-1
List of Preferred Terms for AE Categories of Clinical Interest Created by Narrow SMQs.
..........................................................................................................................................48
Table 8-2
List of Preferred Terms for Hepatic Disorder Broad SMQ ..............................................79
2.2
List of Figures


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3.
List of Abbreviations and Definition of Terms
Table 3-1
Abbreviations and Definitions of Terms
Abbreviation/Term
Definition
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
BMI
body mass index
C-SSRS
Columbia–Suicide Severity Rating Scale
CFB
change from baseline
CHD
coronary heart disease
CSR
clinical study report
CV
cardiovascular
eCRF
electronic case report form
ECG
electrocardiogram, electrocardiographic
FDS
Functional Disability Scale
HEOR
Health Economics and Outcomes Research
INR
international normalized ratio
IWRS
interactive web response system
kg
kilogram(s)
LOCF
last observation carried forward
m
meter(s)
MedDRA
Medication Dictionary for Regulatory Activities
mg
milligrams
mITT
modified intent-to-treat
MQoLQ
migraine quality of life questionnaire
PCS
potentially clinically significant
PF
pain free
PK
pharmacokinetic
PR
pain relief
PT
preferred term
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
SAS
Statistical Analysis Software
SD
standard deviation
SE
standard error


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Abbreviation/Term
Definition
SI
Le Système International d’Unités (International System of Units)
SOC
system organ class
SPF
sustained pain freedom
TBL
total bilirubin
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
US
United States of America
WHO
World Health Organization


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4.
Introduction
This statistical analysis plan (SAP) details comprehensive, technical specifications of the statistical 
analyses of the efficacy and safety data outlined and/or specified in the protocol amendment #2 dated 06 
Dec 2017 of Study UBR-MD-04. Specifications of tables, figures, and data listings are contained in a 
separate document. The SAP for health economics and outcomes research (HEOR) data will be prepared 
separately.
This document is organized into 3 main sections:
1.
Study overview
2.
Statistical Methodology and Study Endpoints
3.
Data Handling and Analysis Conventions
4.1
Study Design Summary
Structure:  Multicenter, randomized, open-label, 52-week extension study; randomization to the 
ubrogepant arms (50 and 100 mg) will be blinded.
Duration:  52 weeks
Study Treatment Groups:  usual care, ubrogepant 50 mg, or ubrogepant 100 mg
Controls:  Not applicable
Dosage/Dose Regimen:  Patients randomized to either of the ubrogepant arms will treat up to 8 migraine 
attacks (of any pain severity) every 4 weeks at home for a total 1 year. Patients have the option to take a 
second dose of ubrogepant if the patient has either a nonresponding migraine or a migraine recurrence. 
The second dose of ubrogepant will be identical to the first dose. 
Patients randomized to the usual-care arm will be instructed to treat their migraine with medications that 
they routinely use to relieve a migraine attack.
Randomization/
  Patients will be randomized (1:1:1) to 1 of the following 3 treatment 
groups:  usual care, ubrogepant 50 mg, or ubrogepant 100 mg. The study is open-label; however, 
randomization to the ubrogepant arms (50 and 100 mg) will be blinded.
 
Number of Participants:  Approximately 1200 patients will be randomized (400 patients per arm) from 
approximately 200 centers in the United States.
4.2
Study Objectives and Endpoints
Each study objective is presented with corresponding endpoint(s) below:


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Table 4-1
Study Objectives and Corresponding Endpoints 
Objectives
Endpoints
Primary
[PO1] To evaluate the safety and 
tolerability of intermittent treatment 
with ubrogepant for the acute 
treatment of migraine over 1 year
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Objectives
Endpoints
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Assessments

Adverse events (AE), clinical laboratory 
values, vital signs, electrocardiogram (ECG), 
physical examinations, and the Columbia–
Suicide Severity Rating Scale (C-SSRS)


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4.3
Schedule of Activities


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5.
Statistical Methodology and Study Endpoints
5.1
Statistical Methods Planned in the Protocol and Determination of 
Sample Size
This statistical analysis plan (SAP) will be approved prior to database lock. The SAP expands the 
statistical section of the protocol and contains a detailed description of methods to analyze data collected 
in the study. The text portion of the SAP will be included in the clinical study report (CSR) report as 
Appendix 16.1.9. 
5.1.1
Statistical and Analytical Plans
Statistical analyses will be conducted using 
.
5.1.1.1
Common Conventions
5.1.1.1.1
Analysis Populations
The analysis populations will consist of participants as defined below:
Table 5-1
Analysis Populations
Population
Definition
Study Treatment
Screened
All screened participants who signed informed consent
—
Intent-to-Treat (ITT)
All randomized participants.
Randomized assignment
Modified Intent-to-
Treat (mITT)
All randomized patients who received at least 1 dose of IP 
(ubrogepant) and had at least 1 posttreatment efficacy assessment 
in this study. The mITT population is only defined for the 
ubrogepant arms, as no posttreatment efficacy measurements will 
be collected from patients in the usual-care arm.
Randomized assignment
Safety
The Safety population is defined separately below for the 
ubrogepant arms and the usual-care arm. 
Ubrogepant arms: All randomized patients who received ≥ 1 dose 
of treatment.
Usual care arm: All randomized patients in the usual-care arm.  
The purpose of the usual care arm is to contextualize any safety 
findings that may occur in the ubrogepant treated patients over 
the course of 12 months.  As such, data from all patients 
randomized to the usual care arm, regardless of whether the 
patient used medication to treat migraine, will be included in the 
safety analyses.   
Actual received


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5.1.1.1.2
Study Treatments
The following treatment groups are defined for this study:

Usual Care

Ubrogepant 50 mg

Ubrogepant 100 mg
5.1.1.1.3
Statistical Methodology
The methodologies defined below apply as specified to individual endpoints defined in this SAP. All 
statistical tests will be 2-sided hypothesis tests performed at the 5% level of significance for main effects. 
All confidence intervals will be 2-sided 95% confidence intervals, unless stated otherwise.
Table 5-2
Statistical Methodology
Methodology
Description
M1
Categorical 
counts

Number of participants in individual categories
o
Participants with ≥ 1 qualifying event counted once per individual category
M2
Categorical 
descriptives

Number and percentage of participants in individual categories
o
Participants with ≥ 1 qualifying event counted once per individual category

N1 if proportion denominator ≠ number of participants in the population (standard 
percentage denominator)
o
N1 = participants with non-missing baseline value
M3
PCS 
descriptives

Number and percentage of participants meeting potentially clinically significant 
(PCS) criteria
o
Participants with ≥ 1 qualifying event counted once per PCS category 

Percentage denominator = number of participants with all non-missing non-PCS 
baseline and >=1 non-missing postbaseline assessment
o
Unevaluable assessments considered missing
M4
Shift 
analysis

Number and percentage of participants in individual baseline and postbaseline 
categories

Percentage denominator = number of participants in individual baseline categories

N1 = participants with non-missing values at both baseline and the specified 
postbaseline analysis visit
M5
Continuous 
descriptives

N1, mean, standard deviation (SD), median, minimum, maximum

N1 = participants with non-missing value
M6
CFB 
descriptives

Continuous descriptives for baseline, postbaseline, and change from baseline (CFB) 
values

N1 = participants with non-missing values at both baseline and the specified 
postbaseline analysis visit
M7
Responder

Categorical descriptives using proportions for responders and nonresponders
o
Nonresponders include:

Participants who do not meet responder criteria

N1 = all participants unless otherwise specified
M8
Logistic 
regression 
model

Measures the relationship between the binomial dependent variable (number of 
events among number of treated attacks) and independent variables:
o
fixed effect terms: 

treatment (ubrogepant 50 mg, ubrogepant 100 mg)

time

treatment-by-time interaction
o
Random effect term:

patient


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Methodology
Description

Odds ratio for comparing the percentage of treated attacks with PF at 2 hours for a 
given 3-month interval with that for the first 3-month interval and its 95% 
confidence interval will be derived from the mixed logistic regression model for 
each of the 2 ubrogepant treatment groups. 
o
Calculate two-sided p-values
CFB = change from baseline.
Raw and derived data listings will be provided, and will be fully defined in the table, figure, and data listing specification 
document.
5.1.1.1.4
Missing Data
General missing data handling conventions are specified for methodologies in Section 5.1.1.1.3 and 
summarized as follows:
Table 5-3
Missing Data Handling by Endpoint Type
Parameter type
Timing
Missing Data Handling
Responder
Treatment Period

If missing headache severity, migraine-associated symptoms,
use Observed Cases (OC)
A conservative approach will used to resolve the incompatibility between the answers to the headache 
recurrence questions at the 24- and 48-hour time points for each treated attack by setting the answer to the 
recurrence question at the 48-hour time point the same as the answer to the recurrence question at the 24-
hour time point, when the 24-hour time point recurrence question indicates headache recurrence between 
2 and 24 hours but the 48-hour time point recurrence question indicates either no or a less severe 
headache recurrence between 2 and 48 hours for the same treated attack.
 
 


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5.1.1.2
Demographics
5.1.1.2.1
Analysis Populations 
The distribution of participants within the analysis populations will be summarized as follows:
Table 5-4
Analysis Population Summaries
Population 
Description
Timing
Methodology
Screened Population
Distribution overall and within sites in 
total
Distribution by lead-in study treatment and 
within extension study in total
—
Categorical counts
ITT, mITT, and Safety 
populations
Distribution overall and within sites in 
total and by treatment group
Distribution by lead-in study treatment and 
by extension study treatment
—
Categorical counts
5.1.1.2.2
Participant Disposition
Participant disposition encompasses the distribution of participants who enter, complete, and discontinue 
each specified analysis period, along with eCRF-reported discontinuation reasons from each respective 
analysis period. Participant disposition will also be presented for the relevant subgroups including sex, 
age group, race, CV risk category, and renal function class. The subgroups are defined in the lead-in 
studies. Participant disposition will be summarized as follows:
Table 5-5
Participant Disposition Summaries
Parameter
Description
Timing
Methodology
Screening disposition1
Distribution in the Screened Population in 
total
Screening Period
Categorical 
descriptives
Treatment disposition1
Distribution in the Safety Population and 
ITT Population in total and by treatment 
group for all participants and by 
subgroups:

by sex, 

by age group (<40 years vs 
≥40 years)

by age subgroup ( <65 years vs 
≥65 years)

by race (white vs non-white)

by cardiovascular risk category 
(high risk, moderate risk, and low 
risk)

by renal function class (normal, 
Treatment Period
Categorical 
descriptives


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Parameter
Description
Timing
Methodology
mild renal impairment, moderate 
renal impairment)
4 Week Safety Follow-
up disposition1
Distribution in the Safety Population and 
ITT Population in total and by treatment 
group for all participants and by 
subgroups:

by sex, 

by age group (<40 years vs 
≥40 years)

by age subgroup ( <65 years vs 
≥65 years)

by race (white vs non-white)

by cardiovascular risk category 
(high risk, moderate risk, and low 
risk)

by renal function class (normal, 
mild renal impairment, moderate 
renal impairment)
Post-treatment Period
Categorical 
descriptives
1 Participant disposition will be listed and participants who prematurely discontinued will be listed.
CV risk subgroup will be derived as a categorical variable with three categories based on NCEP ATP III: Category 1 (High 
Risk): > 20% 10-year CV risk, Category 2 (Moderate Risk): 10 - 20% 10-year CV risk, and Category 3 (Low Risk): <10% 
10-year CV risk.
Renal function class will be derived as a categorical variable based on baseline eGFR as shown in Table 5-6. Since only a few 
participants are classified into the categories of severe renal impairment or ESRD, renal function class for subgroup analyses will 
focus on the following categories: Normal, Mild renal impairment, Moderate renal impairment. A listing of all AEs for 
participants with severe renal impairment or ESRD will be provided including treatment group, participant ID, study center, and 
baseline eGFR.
Table 5-6
Classification of Renal Function Based on Estimated GFR (eGFR) 
Stage 
Renal Function Class
eGFRa (mL/min/1.73m2) 
1 
Normal
≥ 90 
2 
Mild renal impairment
60-89 
3 
Moderate renal impairment
30-59 
4 
Severe renal impairment
15-29 
5 
End Stage Renal Disease (ESRD)
<15 not on dialysis 
a eGFR: estimate of GFR based on a Modification of Diet in Renal Disease (MDRD) equation.
5.1.1.2.3
Protocol Deviations
Protocol deviations will be defined in Protocol Deviation Requirement Specification, including 
importance classification. Protocol deviations will be summarized as follows:


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Table 5-7
Protocol Deviation Summary
Parameter
Description
Timing
Methodology
Major protocol 
deviations1
Distribution in the ITT Population in total 
and by treatment group
—
Categorical 
descriptives
1 Protocol deviations will be listed.
5.1.1.2.4
Demographics
Demographics will be summarized in total and by treatment group for the ITT, Safety, and mITT
populations, as follows:
Table 5-8
Demographic Summaries
Parameter
Description
Timing
Methodology
Age1
Age (years) relative to informed consent 
date
Informed consent in 
the lead-in study
Continuous 
descriptives
Age group
Age group 1:

<20

20 to 29

30 to 39

40 to 49

50 to 59

60 to 69

≥70
Age group 2:

<40

≥40
Age group 3:

<65

≥65
Informed consent in 
the lead-in study
Categorical 
descriptives
Sex, race, and ethnicity1

eCRF categories

Race group
o
White
o
Non-white
Screening Period in 
the lead-in study
Categorical 
descriptives
1 Participant demographics will be listed.
5.1.1.2.5
Baseline Characteristics
Baseline characteristics will be summarized in total and by treatment group for the ITT, Safety, and mITT
populations as follows:
Table 5-9
Baseline Characteristics Summaries
Parameter
Description
Timing
Methodology
Baseline characteristics1

Height (m)

Weight (kg)

Body mass index (BMI)
o
Weight (kg) / height (m)2
Latest assessment in 
Screening Period in 
the lead-in study
Continuous 
descriptives
Cardiovascular risk2
Cardiovascular risk factor subgroup

low risk

moderate risk

high risk
Randomization date 
in the lead-in study
Categorical 
descriptives


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Parameter
Description
Timing
Methodology
Renal function class2
Renal function class subgroup

Normal

Mild renal impairment

Moderate renal impairment
Randomization date 
in the lead-in study
Categorical 
descriptives
Randomization strata3
Previous response to triptans 

Triptan Responder

Triptan Insufficient Responder

Triptan Naïve
Triptan Insufficient Responder will be 
further classified into subcategories

Insufficient Efficacy

Insufficient Tolerability

Contraindications/Warnings or 
Precautions
Current use of prophylactic concomitant 
medication for migraine (Yes, No)
Randomization date 
in the lead-in study
Categorical 
descriptives
1 Participant baseline characteristics will be listed.
2 Summary for Safety population only.
3 Participant randomization scheme and codes will be listed.
5.1.1.2.6
Medical History
Medical history, encompassing abnormalities and surgeries reported as occurring before the Screening 
Visit in the lead-in study, will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA), version 20.1 or newer. Unique participants who report medical history events will be 
summarized by MedDRA system organ class (SOC) and preferred term (PT) in total and by treatment 
group for the Safety Population as follows:
Table 5-10
Medical History Summary
Parameter
Description
Timing
Methodology
Medical history1
Abnormalities and surgeries occurring 
before the Screening Visit by treatment 
group
Screening Period in 
the lead-in study
Categorical 
descriptives
SOCs will be sorted alphabetically; PTs will be sorted in descending frequency in the highest dose group.
1 Participant medical history will be listed.
5.1.1.2.7
Migraine History
Migraine history (based on the lead-in study), including diagnosis, duration of disorder, previous use of 
prophylaxis treatment, average frequency of moderate to severe migraines per month in past 3 months, 
and acute treatments will be reported in total and by treatment group for the Safety Population as follows:
Table 5-11
Migraine History Summary
Parameter
Description
Timing
Methodology
Migraine Diagnosis1

With Aura

Without Aura

Both
Screening Period 
in the lead-in 
study
Categorical 
descriptives
Previous Prophylaxis 
Migraine Treatment1
Yes or No
Screening Period 
in the lead-in 
study
Categorical 
descriptives
Acute Migraine 
Treatment1
Categorize as Yes or No, and 
subcategorize the Yes by:
Screening Period 
in the lead-in 
Categorical 
descriptives


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Parameter
Description
Timing
Methodology

Triptan

Ergot or Ergot Combinations

NSAID

Opiate or Opiate Combination

Antiemetic Agent

Barbiturates

Other
study
Migraine Disorder 
Duration1
In the Table summarize in Years, in the 
Listing show original data in Years and 
Months
Screening Period 
in the lead-in 
study
Continuous 
descriptives
Average Frequency of 
Moderate to Severe 
Migraines per Month in 
Last 3 Months
N/A
Screening Period 
in the lead-in 
study
Continuous 
descriptives
1 Participant migraine history will be listed.
5.1.1.2.8
Prior and Concomitant Medications
Medications will be coded using the World Health Organization (WHO) Drug Dictionary, version March 
2016 or newer. Unique participants who reported medications will be summarized by Anatomical 
Therapeutic Chemical (ATC) 4 class and PT in total and by treatment group for the Safety Population as 
follows:
Table 5-12
Medication Summaries
Parameter
Description
Timing
Methodology
Prior medications1
Medications taken ≥ 1 time before the 
study treatment start date of the lead-in 
study, regardless of medication end date
Screening Period in 
the lead-in study
Categorical 
descriptives
Concomitant 
medications1
Medications taken ≥ 1 time on or after the 
randomization date, regardless of 
medication start date
Treatment Period
Categorical 
descriptives
ATC4 classes will be sorted alphabetically; PTs will be sorted in descending frequency in the highest dose group.
1 Participant prior and concomitant medication will be listed.
 
 
 
 


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5.1.1.4
Safety Analyses
Safety analyses will be based on the Safety Population.
Baseline assessments for applicable safety endpoints are defined as follows:
Table 5-16
Safety Endpoint Baseline Definitions
Parameter
Description
Timing

Clinical laboratory evaluations

Vital signs

Electrocardiograms (ECGs)
eCRF- or (standardized) vendor-provided 
assessments
Latest non-missing 
assessment before the first
dose of treatment in the 
lead-in study
5.1.1.4.1
Study Treatment Exposure and Compliance
Study treatment exposure will be listed for the Safety Population.
The listing of treatment exposure will indicate whether the participant took the optional second dose in 
addition to the first dose for each attack. 
For safety analyses only, the number of treated migraine attacks will be determined based on the date and 
time (if available from eDiary) doses were taken. Starting with the first dose taken by each participant, 
doses will be sorted based on the date and time (if available from eDiary) each dose was 
taken. Subsequent doses that are separated by at least 2 calendar days or 48 hours will be considered the 
initial treatment for a separate and distinct migraine attack. Doses taken within the 2-calendar day/48-
hour window of the initial dose will be considered as additional doses treating the same attack. As such, 
the treatment label (initial dose or optional second dose) will be ignored. The extent of exposure to study 
treatment will be summarized as follows:


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Table 5-17
Treatment Exposure Summaries
Parameter
Description
Timing
Methodology
Number of participants 
with study participation 
by 3-month interval
For all participants:

total number (%) of participants 
who completed 3 months

total number (%) of participants 
who completed 6 months

total number (%) of participants 
who completed 9 months

total number (%) of participants 
who completed 12 months
Subgroup analyses:

by Sex

by Age Group: <40 vs ≥40

by Age Group: <65 vs ≥65

by Race White vs All other races

by CV risk category

by renal function class
Treatment period
Categorical 
descriptives
Number of participants 
with study participation 
by 3-month interval 
among those who 
treated at least 2 
migraine attacks per 
month on average
during the completed 
interval

total number (%) of participants 
who completed 3 months

total number (%) of participants 
who completed 6 months

total number (%) of participants 
who completed 9 months

total number (%) of participants 
who completed 12 months
Treatment period
Categorical 
descriptives
Number of migraine 
attacks treated over the 
entire duration of the 
study1

total number of migraine attacks 
treated with only one dose

total number of migraine attacks 
treated with two or more doses

total number of doses taken
Treatment period
Continuous 
descriptives
Number of attacks 
treated with study 
treatment per month1

>= 8

>= 6 and < 8

>= 4 and < 6

>= 2 and < 4

< 2
Treatment period
Categorical 
descriptives
Average number of 
attacks treated with 
study treatment per 
month1
For all participants:

>= 8

>= 6 and < 8

>= 4 and < 6

>= 2 and < 4

< 2
Subgroup analyses:

by Sex

by Age Group: <40 vs ≥40

by Age Group: <65 vs ≥65

by Race White vs All other races

by CV risk category

by renal function class
Treatment period
Categorical 
descriptives
Maximum number of 
attacks treated with 
study treatment per 

>= 8

>= 6 and < 8

>= 4 and < 6
Treatment period
Categorical 
descriptives


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Parameter
Description
Timing
Methodology
month, defined as 
maximum of monthly 
total number attacks 
treated with study 
treatment among 
months 1-12 for each 
participant1

>= 2 and < 4

< 2
Number of months with 
the number of attacks 
treated with study 
treatment in each 
category1
For each category:

>= 8

>= 6 and < 8

>= 4 and < 6

>= 2 and < 4

< 2
Treatment period
Categorical 
descriptives
Average number of 
study treatment taken 
per month1

>= 16

>= 14 and < 16

>= 12 and < 14

>= 10 and < 12

>= 8 and < 10

>= 6 and < 8

>= 4 and < 6

>= 2 and < 4

< 2
Treatment period
Categorical 
descriptives
Analysis visits defined in Section 6.2.2.
1 Participants in the ubrogepant treatment arms only. No imputation for the last incomplete month.
Treatment compliance for this study will be summarized as follows:
Table 5-18
Treatment Compliance Summaries
Parameter
Description
Timing
Methodology
Overdosing1
Participants who took more than 2 doses 
within 48 hours or 2 calendar days (if time 
information is not available) 
Listing
1 Participants in the ubrogepant treatment arms only.
5.1.1.4.2
Adverse Events
The following adverse event (AE) terms are defined:
Table 5-19
AE Terms
Term
Description
Treatment-
emergent 
An event that initially occurs or increases in intensity on or after the initial dose of treatment of 
the lead-in study. An event that occurs after Visit 16 for participants with Visit 16, or more than 
30 days after the last visit or last treatment, whichever is later, for participants without Visit 16
will not be considered as treatment-emergent.


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Term
Description
On-therapy
An event where:

Treatment start date of the lead-in study ≤ event start date ≤ Visit 16 for participants with 
Visit 16, or within 30 days after the last visit or last treatment, whichever is later, for 
participants without Visit 16
AEs, encompassing abnormalities and surgeries reported as occurring after the Screening Visit, will be 
coded using MedDRA version 20.1 or newer. Unique participants reporting AEs in the following AE 
categories will be summarized by treatment group for the Safety Population as follows:
Table 5-20
AE Summaries
Parameter
Description
Timing
Methodology
Overall summary
Overall summary only for the following 
categories:

Treatment-emergent AEs 
(TEAEs)

Treatment-related TEAEs

On-therapy serious adverse events 
(SAEs)

Deaths

AEs leading to discontinuation
Subgroup analyses by Cardiovascular Risk 
Category and by renal function class
From randomization date 
to Visit 16 for participants 
with Visit 16, or within 30 
days after last visit or last 
treatment, whichever is 
later, for participants 
without Visit 16
Categorical 
descriptives
TEAEs
Summary by 

SOC and PT for all participants 
and by subgroup analyses:
o
by Sex
o
by Age Group  <40 vs 
≥40
o
by Age Group  <65 vs 
≥65
o
by Race White vs All 
other races
o
by cardiovascular risk 
category
o
by renal function class

SOC and PT for concomitant 
medication classes used by at 
least 10% of participants in at 
least one treatment group

SOC, PT, and AE onset time 
intervals
o
<3 months
o
≥3 and <6 months
o
≥6 and <9 months
o
≥9 and <12 months
o
≥12 months

SOC, PT, and average number of 
migraine attacks treated with 
study treatment per month
o
≥2 
o
≥4
o
≥6
From randomization date 
to Visit 16 for participants 
with Visit 16, or within 30 
days after last visit or last 
treatment, whichever is 
later, for participants 
without Visit 16
Categorical 
descriptives


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Parameter
Description
Timing
Methodology
o
≥8

SOC, PT, and severity 

SOC, PT, and causal relationship 
to the study treatment

Type (Mild, Moderate, Severe, 
related, not related)

SOC and PT for TEAEs occurring 
in ≥ 2% of participants in any 
ubrogepant treated dose group 
(and greater than placebo)
Common TEAEs
Summary by PT

Includes TEAEs occurring in ≥ 
2% of participants in any 
treatment group
From randomization date 
to Visit 16 for participants 
with Visit 16, or within 30 
days after last visit or last 
treatment, whichever is 
later, for participants 
without Visit 16
Categorical 
descriptives
On-therapy SAEs1
Overall summary and by PT
From randomization date 
to Visit 16 for participants 
with Visit 16, or within 30 
days after last visit or last 
treatment, whichever is 
later, for participants 
without Visit 16
Categorical 
descriptives
On-therapy fatal SAEs
Participants who report On-therapy fatal 
SAEs will have their fatal SAEs and all 
AEs listed
From randomization date 
to Visit 16 for participants 
with Visit 16, or within 30 
days after last visit or last 
treatment, whichever is 
later, for participants 
without Visit 16
Categorical 
descriptives
AEs leading to 
discontinuation2
Overall summary and by PT
From randomization date 
to Visit 16 for participants 
with Visit 16, or within 30 
days after last visit or last 
treatment, whichever is 
later, for participants 
without Visit 162
Categorical 
descriptives
TEAEs of specific 
interest3
Overall summary and by PT for the 
following type of TEAEs:

Hepatic Injury TEAEs

Cardiac Arrhythmias TEAEs

Central Nervous System Vascular 
Disorders TEAEs

Embolic and Thrombotic Events 
TEAEs

Hypertension TEAEs

Ischaemic Heart Disease TEAEs

Suicide/self-injury TEAEs

Triptan-associated TEAEs

Abuse-related TEAEs
From randomization date 
to Visit 16 for participants 
with Visit 16, or within 30 
days after last visit or last 
treatment, whichever is 
later, for participants 
without Visit 16
Categorical 
descriptives
SOCs will be sorted alphabetically; PTs will be sorted in descending frequency in the highest dose group.
If more than 1 AE is coded to the same participant, the participant will be counted only once for that preferred term using the 
greatest severity


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Parameter
Description
Timing
Methodology
If more than 1 AE is coded to the same participant, the participant will be counted only once for that preferred term using the 
strictest causal relationship to treatment for the summarization by causal relationship
1 Participants who report ≥ 1 SAE will have their SAE listed.
2 If the discontinued date is from randomization date to Visit 16 for participants with Visit 16, or within 30 days after last visit or 
last treatment, whichever is later, for participants without Visit 16, then AEs leading to discontinuation will be summarized and 
listed
3 Participants who reported ≥ 1 AEs in the corresponding category will have these AEs listed.
5.1.1.4.3
Clinical Laboratory Assessments
Clinical laboratory assessments will be summarized by treatment group for the Safety Population as 
follows:
Table 5-21
Clinical Laboratory Summaries
Endpoint
Description
Timing
Methodology
Number and percentage 
of participants with 
Potentially Clinically 
Significant (PCS) 
values1
Summary by laboratory category, 
parameter, and PCS criteria

Parameters and PCS criteria 
specified in Section 6.3.5.1

N1 (percentage denominator) = 
Participants with non-missing 
non-PCS baseline and >=1 
postbaseline parameter 
assessment
Randomization to 
End of Study3
PCS descriptives
Descriptives2
Summary by laboratory category and 
parameter in SI units and in conventional 
units and analysis visit

Parameters specified in 
Section 6.3.5.3
Randomization to 
End of Study3
CFB descriptives
Shift from baseline
Summary by laboratory parameter and 
category  

Low, normal, and high categories 
provided by central laboratory

Parameters specified in 
Section 6.3.5.3
End of Study3
Shift analysis
Liver function findings4
Summary of number and percentage by 
hepatic laboratory parameter and PCS 
categories. Definition of PCS categories 
see Table 6-10 in Section 6.3.4.2.
Randomization to 
End of Study3
Categorical 
descriptives
Adjudication results of 
ALT or AST 
elevations5
Summary of relationship of ALT or AST 
elevation to study medication for 
participants with adjudicated case (i.e., 
ALT ≥ 3xULN and/or AST ≥ 3xULN) by 
the following categories: 

Probable 

Possible

Unlikely 

Insufficient data
Summary will be provided for the 
incidence by number of participants and 
by number of events
Randomization date 
to End of Study3
Categorical 
descriptives
ALT = aspartate aminotransferase; AST = aspartate aminotransferase; TBL = total bilirubin; ALP = alkaline phosphatase; INR = 
international normalized ratio; ULN = upper limit of normal.
1 Participants who report ≥ 1 postbaseline PCS value will have their laboratory visits with PCS values and all AEs listed.
2 Clinical laboratory results and comments will be listed.
3 Analysis visits defined in Section 6.2.2.


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Endpoint
Description
Timing
Methodology
4 Details of all participants with any liver function laboratory findings will be listed. For participants who met ALT ≥ 3xULN or AST ≥ 
3xULN, their ALT, AST, TBL, ALP, and INR assessments, and all AEs will be listed for all study visits. In addition, if available, their 
abnormal liver biochemistries risk factors, liver disease signs and symptoms, liver diagnostic tests, specialist consultation, liver lab tests, 
and drug screen will also be listed.  
5 Participants with at least one adjudicated case (i.e. ALT ≥ 3xULN or AST ≥ 3xULN) will be listed with their ALT and AST 
assessments, adjudication dates, adjudication results and confounding factors for all study visits.
Evaluation of drug-induced serious hepatoxicity (eDISH) plot (scatter plot of maximum total bilirubin vs. 
maximum ALT) will be generated. The ALT, AST, total bilirubin, and ALP values over time will be 
overlaid on the same plot along with indicators for dosing times for each participant with ALT or AST 
elevation (≥ 3 × ULN).
5.1.1.4.3.1
Potential Hy’s Law
Potential Hy’s Law criteria will be summarized by treatment group for the Safety Population as follows:
Table 5-22
Potential Hy's Law Summaries
Endpoint
Description
Timing
Methodology
Potential Hy’s Law 
within 24-hour window
Number and percentage of participants 
with postbaseline assessment of the 
following laboratory parameters based on 
blood draws collected within a 24-hour 
period:

ALT or AST ≥ 3 × ULN

TBL ≥ 2 × ULN

ALP < 2 × ULN
Randomization to 
End of Study1
Categorical 
descriptives
Potential Hy’s Law 
without window
(e-DISH)
Number and percentage of participants 
with postbaseline assessment of the 
following laboratory parameters at any 
time:

Maximum ALT or AST ≥ 3 × 
ULN

Maximum TBL ≥ 2 × ULN
Randomization to 
End of Study1
Categorical 
descriptives
e-DISH = evaluation of drug-induced serious hepatotoxicity.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBL = total bilirubin.
ALP = alkaline phosphatase; ULN = upper limit of normal.
1 Analysis visits defined in Section 6.2.2.
Participants who meet the Potential Hy’s Law criteria will have their ALT, AST, TBL, and ALP 
assessment listed for all study visits.
5.1.1.4.4
Vital Signs
Vital signs will be summarized by treatment group for the Safety Population as follows:
Table 5-23
Vital Signs Summaries
Endpoint
Description
Timing
Methodology
PCS values1
Summary of number and percentage of 
participants by parameter and PCS criteria

Parameters and PCS criteria specified in 
Section 6.3.6.1
Randomization to 
End of Study1
PCS descriptives
Descriptives3
Summary by parameter and analysis visit

Parameters specified in Section  6.3.6.2
Randomization to 
End of Study2
CFB descriptives
Measures 
Summary of number number and percentage of 
Randomization to 
Summary


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Endpoint
Description
Timing
Methodology
meeting criteria4
participants with post-treatment vital sign
measurement meeting any of following criteria 
will by treatment group:

Systolic Blood Pressure: < 90 mmHg, > 
140 mmHg, > 160 mmHg

Diastolic Blood Pressure: < 50 mmHg, > 
90 mmHg, > 100 mmHg

Pulse Rate: < 60 bpm, > 100 bpm

Temperature: > 38.0 °C, < 36.0 °C

Respiratory rate: < 12 breaths/min, > 20 
breaths/min
End of Study2
1 Participants who report ≥ 1 postbaseline PCS value will have their vital sign visits with PCS values and all AEs listed. 
2 Analysis visits defined in Section 6.2.2.
3 Participant vital signs will be listed.
4 A listing of AEs for participants with postbaseline values meeting the criteria will be also provided.
5.1.1.4.5
Electrocardiograms
Electrocardiograms (ECGs) will be summarized by treatment group for the Safety Population as follows:
Table 5-24
ECG Summaries
Endpoint
Description
Timing
Methodology
PCS values1
Summary of number and percentage of 
participants by parameter and PCS criteria

Parameters and PCS criteria 
specified in Section 6.3.7.2

N1 (percentage denominator) = 
Participants with non-missing 
non-PCS baseline and >=1 
postbaseline parameter 
assessment
Randomization to 
End of Study2
PCS descriptives
Descriptives
Summary by parameter and analysis visit

Parameters specified in Section 
6.3.7.3
Randomization to 
End of Study2
CFB descriptives
Shift from baseline
Summary by parameter and category

Normal; abnormal, not clinically 
significant; abnormal, clinically 
significant provided by
investigator

Parameters specified in Section 
6.3.7.3
End of Study2
Shift analysis
Clinically significant 
ECG abnormalities
A listing showing ECG parameters for 
participants with postbaseline clinically 
significant ECG abnormalities according 
to the investigator’s overall interpretation
Randomization to 
End of Study2
Listing
Descriptives of 
measures meeting 
criteria
Summary of number and percentage of 
participants with post-treatment QTcF 
>450 ms, >480 ms, and >500 ms will be 
tabulated by treatment group
Randomization to 
End of Study2
Descriptives
1 Participants who report ≥ 1 postbaseline PCS value will have their ECG visits with PCS values and all AEs listed. 
2 Analysis visits defined in Section 6.2.2.


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5.1.1.4.6
Cardiovascular Risk
Patients will be categorized into 1 of 3 coronary heart disease (CHD) risk subgroups (low, moderate, or 
high risk) based on NCEP ATP III guideline. Subgroup analyses of TEAEs by cardiovascular (CV) risk 
category will be provided for the Safety Population. 
Table 5-25
Cardiovascular Risk Summaries
Endpoint
Description
Timing
Methodology
TEAEs

Subgroup analyses by CV risk 
category for overall summary and 
by SOC and PT
From randomization
date to Visit 16 for 
participants with 
Visit 16, or within 
30 days after last 
visit or last 
treatment, 
whichever is later,
for participants 
without Visit 16
Categorical 
descriptives
5.1.1.4.7
Suicidality Analyses
Suicidality will be summarized by treatment group for the Safety Population as follows:
Table 5-26
Suicidality Summaries
Endpoint
Description
Timing
Methodology
C-SSRS1
Summary by number and percentage of 
participants with suicidal ideation and 
suicidal behavior for each study phase 
listed in the timing column
Lifetime History, 6 
months prior to 
Screening in the 
lead-in study,
Treatment phase, 
Safety Follow-up 
phase
Categorical 
descriptives
1 Participants with all values, including participant number, treatment group, visit number, intensity of suicidal ideation, suicidal 
behavior type, and lethality of suicidal behavior will be listed.
5.1.1.5
Subgroup Analyses
Subgroups analyses will be done for disposition (Table 5-6), treatment exposure (Table 5-16), and TEAEs 
(Table 5-19) for sex, age group (<40 vs ≥40, and <65 vs ≥65), race (White vs. all other races),
cardiovascular risk category, and renal function class.
5.1.1.6
Interim Analyses
The interim analysis will occur when at least 300 ubrogepant participants (with a minimum of 2 migraines 
treated with ubrogepant per month, on average) have been enrolled in the study for 6 months, and 200 
ubrogepant participants (with a minimum of 2 migraines treated with ubrogepant per month, on average) 
have been enrolled in the study for 1 year.


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The treatment assignments will be unblinded to the Allergan staff for the interim analyses. The interim 
analyses will include all analyses specified in this SAP except for efficacy analyses.
 
 
 
 
5.2
Changes in the Conduct of the Study or Planned Analyses
Prior to database lock, there were no changes in study conduct or planned analyses from what was 
described in the protocol and detailed in the SAP. 
5.2.1
Changes in the Conduct of the Study
Not applicable.
5.2.2
Changes to Analyses Prior to Database Lock
During study UBR-MD-04, it was reported that Participant 
 attempted to conceal her 
pregnancy 
. Therefore, the participant will be 
excluded from the mITT and safety populations, but will remain in the ITT population. This change is 
made after interim lock and prior to the final database lock.


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6.
Data Handling and Analysis Conventions
6.1
Study Treatment Conventions
6.1.1
Analysis Days
Treatment day is defined as follows:
Table 6-1
Analysis Day Definitions
Term
Description
Treatment Day
Relative to randomization date
If analysis date ≥ randomization date:

Day = analysis date – randomization date + 1
o
Day 1 = randomization date
If analysis date < randomization date:

Day = analysis date – randomization date
o
Day -1 = day before randomization date
o
There is no Day 0
6.1.2
Missing/Incomplete Treatment End Date
If the investigator is unable to provide the treatment end date, treatment end date will be imputed to the 
last available dosing record date.
6.2
Analysis Visit Windows
 
 
 
 
 
 
 
 
 
 
e
1X is 1, 2, 3, .... 
 
 


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6.2.2
Safety
The safety analysis visit windows for 3-month time interval are defined as follows:
Table 6-4
Safety Analysis Visit Definitions for 3-Month Time Interval
Analysis Phase
Analysis Visit (Derived)
Window
Treatment 
Completed 3 months
Treatment Day >= 90
Completed 6 months
Treatment Day >= 180
Completed 9 months
Treatment Day >= 270
Completed 12 months
Completing treatment period per 
disposition CRF, or discontinued 
after day 360
Table 6-5
Safety Analysis Visit Definitions for 1-Month Time Interval
Analysis Phase
Analysis Visit (Derived)
Window
Treatment 
Months 1
Treatment Day [1, 30]
Months 2
Treatment Day [31, 60]
Months 3
Treatment Day [61, 90]
Months 4
Treatment Day [91, 120]
Months 5
Treatment Day [121, 150]
Months 6
Treatment Day [151, 180]
Months 7
Treatment Day [181, 210]
Months 8
Treatment Day [211, 240]
Months 9
Treatment Day [241, 270]
Months 10
Treatment Day [271, 300]
Months 11
Treatment Day [301, 330]
Months 12
Treatment Day [331, end of
treatment period]
The analysis visit windows for safety endpoints are defined as follows:
Table 6-6
Safety Analysis Visit Definitions
Analysis Phase
Analysis Visit (Derived)
Scheduled Study Visit (eCRF)
Window
Pretreatment
Baseline
Baseline from Lead-in Study
Treatment Day ≤ 1
Week 4
(Visit 3) Week 4
Treatment Day [2, 42]
Week 8
(Visit 4) Week 8
Treatment Day [43, 70]
Week 12
(Visit 5) Week 12
Treatment Day [71, 98]
Week 16
(Visit 6) Week 16
Treatment Day [99, 126]
Week 20
(Visit 7) Week 20
Treatment Day [127, 154]
Week 24
(Visit 8) Week 24
Treatment Day [155, 182]
Week 28
(Visit 9) Week 28
Treatment Day [183, 210]
Week 32
(Visit 10) Week 32
Treatment Day [211, 238]
Week 36
(Visit 11) Week 36
Treatment Day [239, 266]
Week 40
(Visit 12) Week 40
Treatment Day [267, 294]
Week 44
(Visit 13) Week 44
Treatment Day [295, 322]
Week 48
(Visit 14) Week 48
Treatment Day [323, 350]
Week 52
(Visit 15) Week 52/Early 
Termination
Treatment Day [351, end of 
treatment period]


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Analysis Phase
Analysis Visit (Derived)
Scheduled Study Visit (eCRF)
Window
Safety Follow-up
(Visit 16) 4 Week Safety 
Follow-up
Treatment Day [end of treatment 
period+1, the last study visit]
End of study
Final or termination visit
Latest non-missing assessment 
after randomization date
Safety follow-up visit will be presented in analysis tables for clinical laboratory values and vital signs.
End of Study is defined as the last available assessment during treatment and/or safety follow-up period. End of Study results 
will be presented in analysis tables for safety parameters, including but not limited to electrocardiograms, clinical laboratory 
values, and vital signs.
The following general conventions for repeated or unscheduled assessments will apply unless otherwise 
specified:

The latest non-missing assessment within any analysis window will be flagged as the analysis 
value for any summaries by analysis visit

All postbaseline assessments will be considered for PCS categorization

All assessments will be included in respective listings
 
 


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6.3.4.2
AE Group of Interest
The preferred terms included in each category are based on standardized MedDRA queries (SMQs) or are 
custom created where no SMQ exists or is inadequate (as shown in Table 6-10). 
Table 6-10
Construction Methods for AE Categories of Clinical Interest
Method
Category
Narrow SMQs
Cardiac arrhythmias

Arrhythmia related investigations, signs and symptoms 

Cardiac arrhythmia terms (incl bradyarrhythmias and tachyarrhythmias) 
Central nervous system vascular disorders

Central nervous system haemorrhages and cerebrovascular conditions 

Central nervous system vascular disorders, not specified as haemorrhagic or 
ischaemic 
Embolic and thrombotic events

Embolic and thrombotic events, arterial 

Embolic and thrombotic events, venous 

Embolic and thrombotic events, vessel type unspecified and mixed arterial and 
venous 
Hypertension 
Ischaemic heart disease

Myocardial infarction 

Other ischaemic heart disease 
Suicide/self-injury
Custom created
Hepatic injury

Hepatic disorders (broad SMQ)

Liver transplant (preferred term)
Abuse-related
Triptan-associated


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Method
Category
Note: the categories of clinical interest are listed in bolded italics fonts and constructed from Standard MedDRA 
Query Version 20.1.
The preferred term for the custom-created abuse-related category and triptan-associated category are 
provided in Table 6-11. The lists of preferred terms for AE categories of clinical interest created using 
SMQs are provided in Appendix I.
Table 6-11
Preferred Terms for Abuse-Related Category and Triptan-Associated Category
Category
Preferred Terms
Triptan Associated
chest pain; chest discomfort; throat tightness; asthenia; paraesthesia; dysaesthesia; 
hyperaesthesia
Abuse Related 
Affective disorder; Aggression; Confusional state; Disorientation; Dizziness; Drug 
tolerance; Drug withdrawal syndrome; Euphoric mood; Feeling abnormal; Feeling 
drunk; Feeling of relaxation; Hallucination; Inappropriate affect; Mood altered; 
Psychotic disorder; Somnolence; Substance abuse; Substance dependence; 
Substance use; Substance-induced mood disorder; Substance-induced psychotic 
disorder; Thinking abnormal
6.3.5
Clinical Laboratory Assessments
6.3.5.1
Potentially Clinically Significant Criteria
Laboratory assessments values meeting any of the following PCS low or PCS high criteria will be 
categorized as PCS:
Table 6-12
Clinical Laboratory PCS Criteria
Laboratory
Group
Parameter
SI Unit
PCS Low
Limit
PCS High
Limit
Hematology
Basophils, absolute cell count
109/L
—
> 2.0 × ULN
Eosinophils absolute cell count
109/L
—
> 2 × 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 (thrombocytes)
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
Chemistry
Alanine aminotransferase
U/L
—
> 3 × ULN
Albumin
g/L
< 0.8 × LLN
> 1.2 × ULN


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Laboratory
Group
Parameter
SI Unit
PCS Low
Limit
PCS High
Limit
Alkaline phosphatase
U/L
—
> 3 × ULN
Aspartate aminotransferase
U/L
—
> 3 × 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
Glucose, nonfasting
mmol/L
< 0.8 × LLN
> 2 × 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 (urate)
µmol/L
—
> 1.2 × ULN
Urinalysis
Glucose
mmol/L
—
Positive
pH
pH
< 0.9 × LLN
> 1.1 × ULN
Protein
g/L
—
Positive
Specific gravity
—
—
> 1.1 × ULN
LLN = lower limit of normal (value provided by the laboratory); PCS = potentially clinically significant; SI = Le Système 
International d'Unités (International System of Units); ULN = upper limit of normal (value provided by the laboratory).
6.3.5.2
Hepatic Laboratory Abnormalities
The selected event is of clinical interest: Elevated ALT or AST lab value that is ≥ 3 times the ULN. The 
following laboratory parameters will be summarized:


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Table 6-13
Criteria for Hepatic Laboratory Abnormalities
Laboratory Parameter
Categories
ALT
>= 1 × ULN
>= 1.5 × ULN
>= 2 × ULN
>= 3 × ULN
>= 5 × ULN
>= 10 × ULN
>= 20 × ULN
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


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Laboratory Parameter
Categories
>= 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
LLN = lower limit of normal (value provided by the laboratory); PCS = potentially clinically significant; SI = Le Système 
International d'Unités (International System of Units); ULN = upper limit of normal (value provided by the laboratory).
1 Elevations are from the same day
6.3.5.3
Continuous Descriptives and Shift Table Parameters
The following laboratory parameters will be summarized:
Table 6-14
Clinical Descriptive and Shift Table Parameters
Category
Parameters
Chemistry
Sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, creatinine, total 
bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, 
lactate dehydrogenase, creatine kinase, total protein, albumin, calcium, phosphorus, uric 
acid, total cholesterol, high density lipoprotein, low density lipoprotein, total 
triglycerides
Hematology
Hemoglobin; hematocrit; red blood cell count; red blood cell indices (mean corpuscular 
volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration); 
white blood cell count, including differential (neutrophils, lymphocytes, monocytes, 
eosinophils, and basophils); platelet count
Urinalysis
Specific gravity, pH
6.3.5.4
Character Values
Character values (eg, < 5, negative) will be reviewed prior to database lock and converted to numeric for 
analysis as appropriate. These conversions will be documented in the ADaM specifications.
6.3.6
Vital Signs
6.3.6.1
Potentially Clinically Significant Criteria
Vital sign values meeting both the actual value and change from baseline PCS criteria will be categorized 
as PCS:
Table 6-15
Vital Sign PCS Criteria
Vital Sign
Flag
Criterion Value
Change From Baseline or 
Predose
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


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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.
6.3.6.2
Continuous Descriptives and Shift Table Parameters
The following vital sign parameters will be summarized:
Table 6-16
Vital Sign Descriptive and Shift Table Parameters
Parameters
SBP
Respiratory rate
Weight
DBP
Temperature
BMI
Pulse rate
Orthostatic SBP changes1
Orthostatic DBP change1
Orthostatic Pulse rate change1
SBP = Systolic blood pressure. DBP = Diastolic blood pressure. BMI=Body Mass Index.
1Orthostatic pulse rate change equals standing pulse rate minus sitting pulse rate; orthostatic systolic blood pressure change 
equals standing systolic blood pressure minus sitting systolic blood pressure; and orthostatic diastolic blood pressure change 
equals standing diastolic blood pressure minus sitting diastolic blood pressure
6.3.7
Electrocardiograms
6.3.7.1
QTc Derivation
QTc Bazett (QTcB) and QTc Fridericia (QTcF) are derived as follows:
Table 6-17
QTc Derivation
Parameter
Derivation if RR available
Derivation if RR unavailable
QTcB
QT
square root of RR
QT
square root of (60/HR)
QTcF
QT
cubic root of RR
QT
cubic root of (60/HR)
QTcB = QTc Bazett; QTcF = QTcF Fridericia.
6.3.7.2
Potentially Clinically Significant Criteria
ECG values meeting either the actual value or change from baseline PCS high criteria will be categorized 
as PCS:


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Table 6-18
ECG PCS Criteria
Parameter
Unit
Criterion Value
Change from Baseline or 
Predose
QRS duration
msec
≥ 150
—
PR interval
msec
≥ 250
—
QTc (QTcB or QTcF) interval
msec
> 500
Increase of > 60
PCS = potentially clinically significant; QTc = corrected QT interval
QTcB = QTc Bazett; QTcF = QTcF Fridericia.
6.3.7.3
Continuous Descriptives and Shift Table Parameters
The following ECG parameters will be summarized:
Table 6-19
ECG Descriptive and Shift Table Parameters
Parameters
Heart rate
QRS interval
QT interval
PR interval
QTcB
RR interval
QTcF
QTcB = QTc Bazett; QTcF = QTcF Fridericia.
6.4
Imputed Value Listing Conventions
In general, listings will present the actual partial or missing values rather than the imputed values that 
may be used in endpoint derivation. In instances where imputed values will be presented, imputed values 
will be flagged. Actual rules will be fully defined in the table, figure, and data listing specification 
document.
7.
Amendment(s)
In Section 5.1.1.4.2, removed triptan-associated and abuse-related AE from Table 5-19, for Table 5-20, 
triptan-associated and abuse-related TEAE were under TEAE of special interest.
In Table 5-20 (Section 5.1.1.4.2), removed Triptan-associated TEAE from the overall summary row.
In Table 6-4 (Section 6.2.2), updated definition of completing 12 months.
Added details of AE group of special interest (Section 6.3.4.2).
Added Appendix I: Preferred Terms for AE Categories of Clinical Interest Created by SMQs (Section 
8.1).
 
In Section 5.1.1.4.2 added additional analyses of TEAE reported in ≥ 2% of participants in any 
ubrogepant treated dose group (and greater than placebo) sorted by SOC and then by Preferred Term.


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In Section 5.1.1.4.4 added additional analyses of vital signs for measures meeting criteria.
In Section 5.1.1.4.5 added additional analyses of ECG for measures meeting criteria.
 
In Section 6.4.4, imputation method is changed, missing AE will not be imputed. Updated the imputation 
of medication end date in case imputed end date is prior to start date, the end date will be imputed the 
same as the start date.


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8.
Appendices
8.1
Appendix I: Preferred Terms for AE Categories of Clinical 
Interest Created by SMQs.
Table 8-1
List of Preferred Terms for AE Categories of Clinical Interest Created by Narrow 
SMQs. 
Category
Subcategory
SMQ Type
Preferred Term
Central nervous 
system vascular 
disorders (SMQ)
Central nervous system 
haemorrhages and 
cerebrovascular conditions 
(SMQ)
Narrow
Balint's syndrome
Narrow
Basilar artery aneurysm
Narrow
Carotid artery aneurysm
Narrow
Carotid artery dissection
Narrow
Cerebral endovascular aneurysm repair
Narrow
Cerebral reperfusion injury
Narrow
Cerebral ventricular rupture
Narrow
Cerebrovascular accident prophylaxis
Narrow
Charcot-Bouchard microaneurysms
Narrow
Congenital hemiparesis
Narrow
CSF bilirubin positive
Narrow
Delayed ischaemic neurological deficit
Narrow
Hemianaesthesia
Narrow
Hemiasomatognosia
Narrow
Hemiparaesthesia
Narrow
Hemiparesis
Narrow
Hemiplegia
Narrow
Intra-cerebral aneurysm operation
Narrow
Intracranial aneurysm


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Post stroke depression
Narrow
Posthaemorrhagic hydrocephalus
Narrow
Vein of Galen aneurysmal 
malformation
Narrow
Vertebral artery aneurysm
Narrow
Vertebral artery dissection
Narrow
Basal ganglia haematoma
Narrow
Basal ganglia haemorrhage
Narrow
Basal ganglia stroke
Narrow
Basilar artery perforation
Narrow
Brain stem haematoma
Narrow
Brain stem haemorrhage
Narrow
Brain stem microhaemorrhage
Narrow
Brain stem stroke
Narrow
Carotid aneurysm rupture
Narrow
Carotid artery perforation
Narrow
Central nervous system haemorrhage
Narrow
Cerebellar haematoma
Narrow
Cerebellar haemorrhage
Narrow
Cerebellar microhaemorrhage
Narrow
Cerebellar stroke
Narrow
Cerebral aneurysm perforation
Narrow
Cerebral aneurysm ruptured syphilitic
Narrow
Cerebral arteriovenous malformation 
haemorrhagic
Narrow
Cerebral artery perforation
Narrow
Cerebral haematoma


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Cerebral haemorrhage
Narrow
Cerebral haemorrhage foetal
Narrow
Cerebral haemorrhage neonatal
Narrow
Cerebral microhaemorrhage
Narrow
Cerebrovascular accident
Narrow
Cerebrovascular disorder
Narrow
Epidural haemorrhage
Narrow
Extra-axial haemorrhage
Narrow
Extradural haematoma
Narrow
Haemorrhage intracranial
Narrow
Haemorrhagic cerebral infarction
Narrow
Haemorrhagic stroke
Narrow
Haemorrhagic transformation stroke
Narrow
Intracerebral haematoma evacuation
Narrow
Intracranial haematoma
Narrow
Intracranial tumour haemorrhage
Narrow
Intraventricular haemorrhage
Narrow
Intraventricular haemorrhage neonatal
Narrow
Meningorrhagia
Narrow
Perinatal stroke
Narrow
Periventricular haemorrhage neonatal
Narrow
Pituitary haemorrhage
Narrow
Putamen haemorrhage
Narrow
Ruptured cerebral aneurysm
Narrow
Spinal cord haematoma
Narrow
Spinal cord haemorrhage


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Spinal epidural haematoma
Narrow
Spinal epidural haemorrhage
Narrow
Spinal subarachnoid haemorrhage
Narrow
Spinal subdural haematoma
Narrow
Spinal subdural haemorrhage
Narrow
Stroke in evolution
Narrow
Subarachnoid haematoma
Narrow
Subarachnoid haemorrhage
Narrow
Subarachnoid haemorrhage neonatal
Narrow
Subdural haematoma
Narrow
Subdural haematoma evacuation
Narrow
Subdural haemorrhage
Narrow
Subdural haemorrhage neonatal
Narrow
Thalamus haemorrhage
Narrow
Vertebral artery perforation
Narrow
Amaurosis fugax
Narrow
Basal ganglia infarction
Narrow
Basal ganglia stroke
Narrow
Basilar artery occlusion
Narrow
Basilar artery stenosis
Narrow
Basilar artery thrombosis
Narrow
Brachiocephalic arteriosclerosis
Narrow
Brachiocephalic artery occlusion
Narrow
Brachiocephalic artery stenosis
Narrow
Brain hypoxia
Narrow
Brain stem embolism


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Brain stem infarction
Narrow
Brain stem ischaemia
Narrow
Brain stem stroke
Narrow
Brain stem thrombosis
Narrow
Capsular warning syndrome
Narrow
Carotid angioplasty
Narrow
Carotid arterial embolus
Narrow
Carotid arteriosclerosis
Narrow
Carotid artery bypass
Narrow
Carotid artery calcification
Narrow
Carotid artery disease
Narrow
Carotid artery insufficiency
Narrow
Carotid artery occlusion
Narrow
Carotid artery restenosis
Narrow
Carotid artery stenosis
Narrow
Carotid artery stent insertion
Narrow
Carotid artery stent removal
Narrow
Carotid artery thrombosis
Narrow
Carotid endarterectomy
Narrow
Carotid revascularisation
Narrow
Cerebellar artery occlusion
Narrow
Cerebellar artery thrombosis
Narrow
Cerebellar embolism
Narrow
Cerebellar infarction
Narrow
Cerebellar ischaemia
Narrow
Cerebellar stroke


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Cerebral arteriosclerosis
Narrow
Cerebral artery embolism
Narrow
Cerebral artery occlusion
Narrow
Cerebral artery restenosis
Narrow
Cerebral artery stenosis
Narrow
Cerebral artery thrombosis
Narrow
Cerebral gas embolism
Narrow
Cerebral infarction
Narrow
Cerebral infarction foetal
Narrow
Cerebral ischaemia
Narrow
Cerebral microembolism
Narrow
Cerebral revascularisation
Narrow
Cerebral septic infarct
Narrow
Cerebral small vessel ischaemic disease
Narrow
Cerebral thrombosis
Narrow
Cerebral vascular occlusion
Narrow
Cerebral vasoconstriction
Narrow
Cerebral venous thrombosis
Narrow
Cerebrovascular accident
Narrow
Cerebrovascular disorder
Narrow
Cerebrovascular insufficiency
Narrow
Cerebrovascular stenosis
Narrow
Delayed ischaemic neurological deficit
Narrow
Embolic cerebral infarction
Narrow
Embolic stroke
Narrow
Hypoxic-ischaemic encephalopathy


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Inner ear infarction
Narrow
Ischaemic cerebral infarction
Narrow
Ischaemic stroke
Narrow
Lacunar infarction
Narrow
Lacunar stroke
Narrow
Lateral medullary syndrome
Narrow
Migrainous infarction
Narrow
Millard-Gubler syndrome
Narrow
Moyamoya disease
Narrow
Perinatal stroke
Narrow
Post cardiac arrest syndrome
Narrow
Post procedural stroke
Narrow
Precerebral arteriosclerosis
Narrow
Precerebral artery occlusion
Narrow
Reversible cerebral vasoconstriction 
syndrome
Narrow
Reversible ischaemic neurological 
deficit
Narrow
Spinal artery embolism
Narrow
Spinal artery thrombosis
Narrow
Stroke in evolution
Narrow
Subclavian steal syndrome
Narrow
Thalamic infarction
Narrow
Thrombotic cerebral infarction
Narrow
Thrombotic stroke
Narrow
Transient ischaemic attack
Narrow
Vascular encephalopathy


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Vascular stent occlusion
Narrow
Vascular stent restenosis
Narrow
Vascular stent stenosis
Narrow
Vertebral artery occlusion
Narrow
Vertebral artery stenosis
Narrow
Vertebral artery thrombosis
Narrow
Vertebrobasilar insufficiency
Central nervous system 
vascular disorders, not 
specified as haemorrhagic 
or ischaemic (SMQ)
Narrow
Cerebral arteritis
Narrow
Cerebral capillary telangiectasia
Narrow
Cerebral circulatory failure
Narrow
Cerebral congestion
Narrow
Cerebral hypoperfusion
Narrow
Dural arteriovenous fistula
Narrow
Intracranial venous sinus thrombosis
Narrow
Superior sagittal sinus thrombosis
Narrow
Transverse sinus thrombosis
Narrow
Vasculitis cerebral
Suicide/self-injury 
(SMQ)
Narrow
Assisted suicide
Narrow
Columbia suicide severity rating scale 
abnormal
Narrow
Completed suicide
Narrow
Depression suicidal
Narrow
Intentional overdose
Narrow
Intentional self-injury


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Poisoning deliberate
Narrow
Self-injurious ideation
Narrow
Suicidal behaviour
Narrow
Suicidal ideation
Narrow
Suicide attempt
Narrow
Suicide threat
Cardiac arrhythmias 
(SMQ)
Arrhythmia related 
investigations, signs and 
symptoms (SMQ)
Narrow
Chronotropic incompetence
Narrow
Electrocardiogram repolarisation 
abnormality
Narrow
Electrocardiogram RR interval 
prolonged
Narrow
Electrocardiogram U wave inversion
Narrow
Electrocardiogram U wave present
Narrow
Electrocardiogram U-wave abnormality
Narrow
Sudden cardiac death
Cardiac arrhythmia terms 
(incl bradyarrhythmias and 
tachyarrhythmias) (SMQ)
Narrow
Bradyarrhythmia
Narrow
Ventricular asystole
Narrow
Accessory cardiac pathway
Narrow
Adams-Stokes syndrome
Narrow
Agonal rhythm
Narrow
Atrial conduction time prolongation
Narrow
Atrioventricular block
Narrow
Atrioventricular block complete
Narrow
Atrioventricular block first degree


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Atrioventricular block second degree
Narrow
Atrioventricular conduction time 
shortened
Narrow
Atrioventricular dissociation
Narrow
Bifascicular block
Narrow
Brugada syndrome
Narrow
Bundle branch block
Narrow
Bundle branch block bilateral
Narrow
Bundle branch block left
Narrow
Bundle branch block right
Narrow
Conduction disorder
Narrow
Defect conduction intraventricular
Narrow
Electrocardiogram delta waves 
abnormal
Narrow
Electrocardiogram PQ interval 
prolonged
Narrow
Electrocardiogram PQ interval 
shortened
Narrow
Electrocardiogram PR prolongation
Narrow
Electrocardiogram PR shortened
Narrow
Electrocardiogram QRS complex 
prolonged
Narrow
Electrocardiogram QT prolonged
Narrow
Electrocardiogram repolarisation 
abnormality
Narrow
Lenegre's disease
Narrow
Long QT syndrome
Narrow
Paroxysmal atrioventricular block
Narrow
Sinoatrial block


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Trifascicular block
Narrow
Ventricular dyssynchrony
Narrow
Wolff-Parkinson-White syndrome
Narrow
Nodal arrhythmia
Narrow
Nodal rhythm
Narrow
Sinus arrest
Narrow
Sinus arrhythmia
Narrow
Sinus bradycardia
Narrow
Sinus node dysfunction
Narrow
Wandering pacemaker
Narrow
Arrhythmia
Narrow
Heart alternation
Narrow
Heart rate irregular
Narrow
Pacemaker generated arrhythmia
Narrow
Pacemaker syndrome
Narrow
Paroxysmal arrhythmia
Narrow
Pulseless electrical activity
Narrow
Reperfusion arrhythmia
Narrow
Withdrawal arrhythmia
Narrow
Arrhythmia supraventricular
Narrow
Atrial fibrillation
Narrow
Atrial flutter
Narrow
Atrial parasystole
Narrow
Atrial tachycardia
Narrow
Junctional ectopic tachycardia
Narrow
Sinus tachycardia


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Supraventricular extrasystoles
Narrow
Supraventricular tachyarrhythmia
Narrow
Supraventricular tachycardia
Narrow
Anomalous atrioventricular excitation
Narrow
Cardiac fibrillation
Narrow
Cardiac flutter
Narrow
Extrasystoles
Narrow
Tachyarrhythmia
Narrow
Accelerated idioventricular rhythm
Narrow
Cardiac fibrillation
Narrow
Parasystole
Narrow
Rhythm idioventricular
Narrow
Torsade de pointes
Narrow
Ventricular arrhythmia
Narrow
Ventricular extrasystoles
Narrow
Ventricular fibrillation
Narrow
Ventricular flutter
Narrow
Ventricular parasystole
Narrow
Ventricular pre-excitation
Narrow
Ventricular tachyarrhythmia
Narrow
Ventricular tachycardia
Embolic and 
thrombotic events 
(SMQ)
Embolic and thrombotic 
events, arterial (SMQ)
Narrow
Acute aortic syndrome
Narrow
Acute myocardial infarction
Narrow
Amaurosis
Narrow
Amaurosis fugax


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Angioplasty
Narrow
Aortic bypass
Narrow
Aortic embolus
Narrow
Aortic surgery
Narrow
Aortic thrombosis
Narrow
Aortogram abnormal
Narrow
Arterectomy
Narrow
Arterectomy with graft replacement
Narrow
Arterial bypass occlusion
Narrow
Arterial bypass operation
Narrow
Arterial bypass thrombosis
Narrow
Arterial graft
Narrow
Arterial occlusive disease
Narrow
Arterial stent insertion
Narrow
Arterial therapeutic procedure
Narrow
Arterial thrombosis
Narrow
Arteriogram abnormal
Narrow
Arteriogram carotid abnormal
Narrow
Arteriotomy
Narrow
Atherectomy
Narrow
Atherosclerotic plaque rupture
Narrow
Atrial appendage closure
Narrow
Basal ganglia infarction
Narrow
Basilar artery occlusion
Narrow
Basilar artery thrombosis
Narrow
Blindness transient


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Brachiocephalic artery occlusion
Narrow
Capsular warning syndrome
Narrow
Carotid angioplasty
Narrow
Carotid arterial embolus
Narrow
Carotid artery bypass
Narrow
Carotid artery occlusion
Narrow
Carotid artery stent insertion
Narrow
Carotid artery thrombosis
Narrow
Carotid endarterectomy
Narrow
Cerebellar artery occlusion
Narrow
Cerebellar artery thrombosis
Narrow
Cerebral artery embolism
Narrow
Cerebral artery occlusion
Narrow
Cerebral artery thrombosis
Narrow
Cerebral hypoperfusion
Narrow
Cerebrovascular insufficiency
Narrow
Cerebrovascular stenosis
Narrow
Coeliac artery occlusion
Narrow
Coronary angioplasty
Narrow
Coronary arterial stent insertion
Narrow
Coronary artery bypass
Narrow
Coronary artery embolism
Narrow
Coronary artery occlusion
Narrow
Coronary artery reocclusion
Narrow
Coronary artery surgery
Narrow
Coronary artery thrombosis


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Coronary endarterectomy
Narrow
Coronary revascularisation
Narrow
Coronary vascular graft occlusion
Narrow
Embolia cutis medicamentosa
Narrow
Embolism arterial
Narrow
Endarterectomy
Narrow
Femoral artery embolism
Narrow
Hepatic artery embolism
Narrow
Hepatic artery occlusion
Narrow
Hepatic artery thrombosis
Narrow
Hypothenar hammer syndrome
Narrow
Iliac artery embolism
Narrow
Iliac artery occlusion
Narrow
Intra-aortic balloon placement
Narrow
Intraoperative cerebral artery occlusion
Narrow
Ischaemic cerebral infarction
Narrow
Ischaemic stroke
Narrow
Lacunar infarction
Narrow
Leriche syndrome
Narrow
Mesenteric arterial occlusion
Narrow
Mesenteric arteriosclerosis
Narrow
Mesenteric artery embolism
Narrow
Mesenteric artery stenosis
Narrow
Mesenteric artery stent insertion
Narrow
Mesenteric artery thrombosis
Narrow
Myocardial infarction


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Myocardial necrosis
Narrow
Papillary muscle infarction
Narrow
Penile artery occlusion
Narrow
Percutaneous coronary intervention
Narrow
Peripheral arterial occlusive disease
Narrow
Peripheral arterial reocclusion
Narrow
Peripheral artery angioplasty
Narrow
Peripheral artery bypass
Narrow
Peripheral artery occlusion
Narrow
Peripheral artery stent insertion
Narrow
Peripheral artery thrombosis
Narrow
Peripheral embolism
Narrow
Peripheral endarterectomy
Narrow
Popliteal artery entrapment syndrome
Narrow
Post procedural myocardial infarction
Narrow
Postinfarction angina
Narrow
Precerebral artery occlusion
Narrow
Precerebral artery thrombosis
Narrow
Profundaplasty
Narrow
Pulmonary artery occlusion
Narrow
Pulmonary artery therapeutic procedure
Narrow
Pulmonary artery thrombosis
Narrow
Pulmonary endarterectomy
Narrow
Pulmonary tumour thrombotic 
microangiopathy
Narrow
Renal artery angioplasty


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Renal artery occlusion
Narrow
Renal artery thrombosis
Narrow
Renal embolism
Narrow
Retinal artery embolism
Narrow
Retinal artery occlusion
Narrow
Retinal artery thrombosis
Narrow
Silent myocardial infarction
Narrow
Spinal artery embolism
Narrow
Spinal artery thrombosis
Narrow
Splenic artery thrombosis
Narrow
Splenic embolism
Narrow
Stress cardiomyopathy
Narrow
Subclavian artery embolism
Narrow
Subclavian artery occlusion
Narrow
Subclavian artery thrombosis
Narrow
Superior mesenteric artery syndrome
Narrow
Thromboembolectomy
Narrow
Thrombotic microangiopathy
Narrow
Thrombotic thrombocytopenic purpura
Narrow
Transient ischaemic attack
Narrow
Truncus coeliacus thrombosis
Narrow
Vascular pseudoaneurysm thrombosis
Narrow
Vertebral artery occlusion
Narrow
Vertebral artery thrombosis
Narrow
Visual acuity reduced transiently
Embolic and thrombotic 
Narrow
Axillary vein thrombosis


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Category
Subcategory
SMQ Type
Preferred Term
events, venous (SMQ)
Narrow
Brachiocephalic vein occlusion
Narrow
Brachiocephalic vein thrombosis
Narrow
Budd-Chiari syndrome
Narrow
Catheterisation venous
Narrow
Cavernous sinus thrombosis
Narrow
Central venous catheterisation
Narrow
Cerebral venous thrombosis
Narrow
Compression garment application
Narrow
Deep vein thrombosis
Narrow
Deep vein thrombosis postoperative
Narrow
Embolism venous
Narrow
Hepatic vein embolism
Narrow
Hepatic vein occlusion
Narrow
Hepatic vein thrombosis
Narrow
Homans' sign positive
Narrow
Iliac vein occlusion
Narrow
Inferior vena cava syndrome
Narrow
Inferior vena caval occlusion
Narrow
Intracranial venous sinus thrombosis
Narrow
Jugular vein occlusion
Narrow
Jugular vein thrombosis
Narrow
Mahler sign
Narrow
May-Thurner syndrome
Narrow
Mesenteric vein thrombosis
Narrow
Mesenteric venous occlusion


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Obstetrical pulmonary embolism
Narrow
Obstructive shock
Narrow
Ophthalmic vein thrombosis
Narrow
Ovarian vein thrombosis
Narrow
Paget-Schroetter syndrome
Narrow
Pelvic venous thrombosis
Narrow
Penile vein thrombosis
Narrow
Phlebectomy
Narrow
Portal vein cavernous transformation
Narrow
Portal vein occlusion
Narrow
Portal vein thrombosis
Narrow
Portosplenomesenteric venous 
thrombosis
Narrow
Post procedural pulmonary embolism
Narrow
Post thrombotic syndrome
Narrow
Postoperative thrombosis
Narrow
Postpartum venous thrombosis
Narrow
Pulmonary embolism
Narrow
Pulmonary infarction
Narrow
Pulmonary microemboli
Narrow
Pulmonary thrombosis
Narrow
Pulmonary vein occlusion
Narrow
Pulmonary veno-occlusive disease
Narrow
Pulmonary venous thrombosis
Narrow
Renal vein embolism
Narrow
Renal vein occlusion


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Renal vein thrombosis
Narrow
Retinal vein occlusion
Narrow
Retinal vein thrombosis
Narrow
SI QIII TIII pattern
Narrow
Splenic vein occlusion
Narrow
Splenic vein thrombosis
Narrow
Subclavian vein occlusion
Narrow
Subclavian vein thrombosis
Narrow
Superior sagittal sinus thrombosis
Narrow
Superior vena cava occlusion
Narrow
Superior vena cava syndrome
Narrow
Thrombophlebitis
Narrow
Thrombophlebitis migrans
Narrow
Thrombophlebitis neonatal
Narrow
Thrombophlebitis superficial
Narrow
Thrombosed varicose vein
Narrow
Thrombosis corpora cavernosa
Narrow
Transverse sinus thrombosis
Narrow
Vena cava embolism
Narrow
Vena cava filter insertion
Narrow
Vena cava filter removal
Narrow
Vena cava thrombosis
Narrow
Venogram abnormal
Narrow
Venoocclusive disease
Narrow
Venoocclusive liver disease
Narrow
Venous angioplasty


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Venous occlusion
Narrow
Venous operation
Narrow
Venous recanalisation
Narrow
Venous repair
Narrow
Venous stent insertion
Narrow
Venous thrombosis
Narrow
Venous thrombosis in pregnancy
Narrow
Venous thrombosis limb
Narrow
Venous thrombosis neonatal
Narrow
Visceral venous thrombosis
Embolic and thrombotic 
events, vessel type 
unspecified and mixed 
arterial and venous (SMQ)
Narrow
Administration site thrombosis
Narrow
Adrenal thrombosis
Narrow
Angiogram abnormal
Narrow
Angiogram cerebral abnormal
Narrow
Angiogram peripheral abnormal
Narrow
Application site thrombosis
Narrow
Arteriovenous fistula occlusion
Narrow
Arteriovenous fistula thrombosis
Narrow
Arteriovenous graft thrombosis
Narrow
Artificial blood vessel occlusion
Narrow
Atrial thrombosis
Narrow
Basal ganglia stroke
Narrow
Bone infarction
Narrow
Brain stem embolism


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Brain stem infarction
Narrow
Brain stem stroke
Narrow
Brain stem thrombosis
Narrow
Cardiac ventricular thrombosis
Narrow
Catheter site thrombosis
Narrow
Cerebellar embolism
Narrow
Cerebellar infarction
Narrow
Cerebral congestion
Narrow
Cerebral infarction
Narrow
Cerebral infarction foetal
Narrow
Cerebral ischaemia
Narrow
Cerebral microembolism
Narrow
Cerebral septic infarct
Narrow
Cerebral thrombosis
Narrow
Cerebral vascular occlusion
Narrow
Cerebrospinal thrombotic tamponade
Narrow
Cerebrovascular accident
Narrow
Cerebrovascular accident prophylaxis
Narrow
Cerebrovascular disorder
Narrow
Cerebrovascular operation
Narrow
Choroidal infarction
Narrow
Collateral circulation
Narrow
Coronary bypass thrombosis
Narrow
Device embolisation
Narrow
Device occlusion
Narrow
Device related thrombosis


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Diplegia
Narrow
Directional Doppler flow tests 
abnormal
Narrow
Disseminated intravascular coagulation
Narrow
Disseminated intravascular coagulation 
in newborn
Narrow
Embolic cerebral infarction
Narrow
Embolic pneumonia
Narrow
Embolic stroke
Narrow
Embolism
Narrow
Foetal cerebrovascular disorder
Narrow
Graft thrombosis
Narrow
Haemorrhagic adrenal infarction
Narrow
Haemorrhagic cerebral infarction
Narrow
Haemorrhagic infarction
Narrow
Haemorrhagic stroke
Narrow
Haemorrhagic transformation stroke
Narrow
Haemorrhoids thrombosed
Narrow
Hemiparesis
Narrow
Hemiplegia
Narrow
Heparin-induced thrombocytopenia
Narrow
Hepatic infarction
Narrow
Hepatic vascular thrombosis
Narrow
Implant site thrombosis
Narrow
Incision site vessel occlusion
Narrow
Infarction
Narrow
Infusion site thrombosis


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Injection site thrombosis
Narrow
Inner ear infarction
Narrow
Instillation site thrombosis
Narrow
Intestinal infarction
Narrow
Intracardiac mass
Narrow
Intracardiac thrombus
Narrow
Medical device site thrombosis
Narrow
Mesenteric vascular insufficiency
Narrow
Mesenteric vascular occlusion
Narrow
Microembolism
Narrow
Monoparesis
Narrow
Monoplegia
Narrow
Optic nerve infarction
Narrow
Pancreatic infarction
Narrow
Paradoxical embolism
Narrow
Paraneoplastic thrombosis
Narrow
Paraparesis
Narrow
Paraplegia
Narrow
Paresis
Narrow
Peripheral revascularisation
Narrow
Pituitary infarction
Narrow
Placental infarction
Narrow
Pneumatic compression therapy
Narrow
Portal shunt procedure
Narrow
Post procedural stroke
Narrow
Postpartum thrombosis


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Ubrogepant
72
Category
Subcategory
SMQ Type
Preferred Term
Narrow
Prosthetic vessel implantation
Narrow
Quadriparesis
Narrow
Quadriplegia
Narrow
Renal infarct
Narrow
Renal vascular thrombosis
Narrow
Retinal infarction
Narrow
Retinal vascular thrombosis
Narrow
Shunt occlusion
Narrow
Shunt thrombosis
Narrow
Spinal cord infarction
Narrow
Splenic infarction
Narrow
Splenic thrombosis
Narrow
Stoma site thrombosis
Narrow
Stroke in evolution
Narrow
Surgical vascular shunt
Narrow
Testicular infarction
Narrow
Thalamic infarction
Narrow
Thrombectomy
Narrow
Thromboangiitis obliterans
Narrow
Thrombolysis
Narrow
Thrombosis
Narrow
Thrombosis in device
Narrow
Thrombosis mesenteric vessel
Narrow
Thrombosis prophylaxis
Narrow
Thrombotic cerebral infarction
Narrow
Thrombotic stroke


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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Thyroid infarction
Narrow
Tumour embolism
Narrow
Tumour thrombosis
Narrow
Ultrasonic angiogram abnormal
Narrow
Ultrasound Doppler abnormal
Narrow
Umbilical cord occlusion
Narrow
Umbilical cord thrombosis
Narrow
Vaccination site thrombosis
Narrow
Vascular access site thrombosis
Narrow
Vascular graft
Narrow
Vascular graft occlusion
Narrow
Vascular graft thrombosis
Narrow
Vascular operation
Narrow
Vascular stent insertion
Narrow
Vascular stent occlusion
Narrow
Vascular stent thrombosis
Narrow
Vasodilation procedure
Narrow
Vessel puncture site occlusion
Narrow
Vessel puncture site thrombosis
Narrow
Visual midline shift syndrome
Hypertension (SMQ)
Narrow
Accelerated hypertension
Narrow
Blood pressure ambulatory increased
Narrow
Blood pressure diastolic increased
Narrow
Blood pressure inadequately controlled
Narrow
Blood pressure increased
Narrow
Blood pressure management


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Ubrogepant
74
Category
Subcategory
SMQ Type
Preferred Term
Narrow
Blood pressure orthostatic increased
Narrow
Blood pressure systolic increased
Narrow
Diastolic hypertension
Narrow
Eclampsia
Narrow
Endocrine hypertension
Narrow
Essential hypertension
Narrow
Gestational hypertension
Narrow
HELLP syndrome
Narrow
Hyperaldosteronism
Narrow
Hypertension
Narrow
Hypertension neonatal
Narrow
Hypertensive angiopathy
Narrow
Hypertensive cardiomegaly
Narrow
Hypertensive cardiomyopathy
Narrow
Hypertensive cerebrovascular disease
Narrow
Hypertensive crisis
Narrow
Hypertensive emergency
Narrow
Hypertensive encephalopathy
Narrow
Hypertensive end-organ damage
Narrow
Hypertensive heart disease
Narrow
Hypertensive nephropathy
Narrow
Labile hypertension
Narrow
Malignant hypertension
Narrow
Malignant hypertensive heart disease
Narrow
Malignant renal hypertension
Narrow
Maternal hypertension affecting foetus


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Ubrogepant
75
Category
Subcategory
SMQ Type
Preferred Term
Narrow
Mean arterial pressure increased
Narrow
Metabolic syndrome
Narrow
Neurogenic hypertension
Narrow
Orthostatic hypertension
Narrow
Page kidney
Narrow
Pre-eclampsia
Narrow
Prehypertension
Narrow
Procedural hypertension
Narrow
Renal hypertension
Narrow
Renal sympathetic nerve ablation
Narrow
Renovascular hypertension
Narrow
Retinopathy hypertensive
Narrow
Secondary aldosteronism
Narrow
Secondary hypertension
Narrow
Supine hypertension
Narrow
Systolic hypertension
Narrow
Withdrawal hypertension
Ischaemic heart 
disease (SMQ)
Myocardial infarction 
(SMQ)
Narrow
Acute coronary syndrome
Narrow
Acute myocardial infarction
Narrow
Angina unstable
Narrow
Blood creatine phosphokinase MB 
abnormal
Narrow
Blood creatine phosphokinase MB 
increased
Narrow
Coronary artery embolism
Narrow
Coronary artery occlusion


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Ubrogepant
76
Category
Subcategory
SMQ Type
Preferred Term
Narrow
Coronary artery reocclusion
Narrow
Coronary artery thrombosis
Narrow
Coronary bypass thrombosis
Narrow
Coronary vascular graft occlusion
Narrow
Kounis syndrome
Narrow
Myocardial infarction
Narrow
Myocardial necrosis
Narrow
Myocardial reperfusion injury
Narrow
Myocardial stunning
Narrow
Papillary muscle infarction
Narrow
Periprocedural myocardial infarction
Narrow
Post procedural myocardial infarction
Narrow
Postinfarction angina
Narrow
Silent myocardial infarction
Narrow
Troponin I increased
Narrow
Troponin increased
Narrow
Troponin T increased
Other ischaemic heart 
disease (SMQ)
Narrow
Angina pectoris
Narrow
Angina unstable
Narrow
Anginal equivalent
Narrow
Arteriosclerosis coronary artery
Narrow
Arteriospasm coronary
Narrow
Coronary angioplasty
Narrow
Coronary arterial stent insertion
Narrow
Coronary artery bypass
Narrow
Coronary artery compression


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Ubrogepant
77
Category
Subcategory
SMQ Type
Preferred Term
Narrow
Coronary artery disease
Narrow
Coronary artery dissection
Narrow
Coronary artery insufficiency
Narrow
Coronary artery restenosis
Narrow
Coronary artery stenosis
Narrow
Coronary artery surgery
Narrow
Coronary brachytherapy
Narrow
Coronary bypass stenosis
Narrow
Coronary endarterectomy
Narrow
Coronary no-reflow phenomenon
Narrow
Coronary ostial stenosis
Narrow
Coronary revascularisation
Narrow
Coronary vascular graft stenosis
Narrow
Dissecting coronary artery aneurysm
Narrow
ECG signs of myocardial ischaemia
Narrow
External counterpulsation
Narrow
Haemorrhage coronary artery
Narrow
Ischaemic cardiomyopathy
Narrow
Ischaemic mitral regurgitation
Narrow
Microvascular coronary artery disease
Narrow
Myocardial hypoxia
Narrow
Myocardial ischaemia
Narrow
Percutaneous coronary intervention
Narrow
Prinzmetal angina
Narrow
Stress cardiomyopathy
Narrow
Subclavian coronary steal syndrome


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Ubrogepant
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Category
Subcategory
SMQ Type
Preferred Term
Narrow
Subendocardial ischaemia


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SAP UBR-MD-04
Ubrogepant
79
Table 8-2
List of Preferred Terms for Hepatic Disorder Broad SMQ 
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Congenital, familial, neonatal 
and genetic disorders of the 
liver (SMQ)
Narrow
Accessory liver lobe
Narrow
Alagille syndrome
Narrow
Cerebrohepatorenal syndrome
Narrow
Congenital absence of bile ducts
Narrow
Congenital cystic disease of liver
Narrow
Congenital hepatic fibrosis
Narrow
Congenital hepatobiliary anomaly
Narrow
Congenital hepatomegaly
Narrow
Cystic fibrosis hepatic disease
Narrow
Dilatation intrahepatic duct congenital
Narrow
Glycogen storage disease type I
Narrow
Glycogen storage disease type III
Narrow
Glycogen storage disease type IV
Narrow
Glycogen storage disease type VI
Narrow
Hepatic hamartoma
Narrow
Hepatitis neonatal
Narrow
Hepatocellular damage neonatal
Narrow
Hepato-lenticular degeneration
Narrow
Hepatosplenomegaly neonatal
Narrow
Hereditary haemochromatosis
Narrow
Neonatal cholestasis


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Ubrogepant
80
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Neonatal hepatomegaly
Narrow
Polycystic liver disease
Narrow
Porphyria acute
Narrow
Portal venous system anomaly
Narrow
Progressive familial intrahepatic cholestasis
Broad
Hyperbilirubinaemia neonatal
Broad
Jaundice neonatal
Broad
Kernicterus
Broad
Porphyria non-acute
Drug related hepatic disorders -
comprehensive search (SMQ)
Narrow
Bilirubin excretion disorder
Narrow
Cholaemia
Narrow
Cholestasis
Narrow
Cholestatic liver injury
Narrow
Cholestatic pruritus
Narrow
Drug-induced liver injury
Narrow
Hepatitis cholestatic
Narrow
Hyperbilirubinaemia
Narrow
Icterus index increased
Narrow
Jaundice
Narrow
Jaundice cholestatic
Narrow
Jaundice hepatocellular
Narrow
Mixed liver injury
Narrow
Ocular icterus


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
81
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Parenteral nutrition associated liver disease
Broad
Deficiency of bile secretion
Broad
Yellow skin
Narrow
Acute hepatic failure
Narrow
Acute on chronic liver failure
Narrow
Acute yellow liver atrophy
Narrow
Ascites
Narrow
Asterixis
Narrow
Bacterascites
Narrow
Biliary cirrhosis
Narrow
Biliary cirrhosis primary
Narrow
Biliary fibrosis
Narrow
Cholestatic liver injury
Narrow
Chronic hepatic failure
Narrow
Coma hepatic
Narrow
Cryptogenic cirrhosis
Narrow
Diabetic hepatopathy
Narrow
Drug-induced liver injury
Narrow
Duodenal varices
Narrow
Gallbladder varices
Narrow
Gastric variceal injection
Narrow
Gastric variceal ligation
Narrow
Gastric varices


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
82
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Gastric varices haemorrhage
Narrow
Hepatectomy
Narrow
Hepatic atrophy
Narrow
Hepatic calcification
Narrow
Hepatic cirrhosis
Narrow
Hepatic encephalopathy
Narrow
Hepatic encephalopathy prophylaxis
Narrow
Hepatic failure
Narrow
Hepatic fibrosis
Narrow
Hepatic hydrothorax
Narrow
Hepatic infiltration eosinophilic
Narrow
Hepatic lesion
Narrow
Hepatic necrosis
Narrow
Hepatic steato-fibrosis
Narrow
Hepatic steatosis
Narrow
Hepatitis fulminant
Narrow
Hepatobiliary disease
Narrow
Hepatocellular foamy cell syndrome
Narrow
Hepatocellular injury
Narrow
Hepatopulmonary syndrome
Narrow
Hepatorenal failure
Narrow
Hepatorenal syndrome
Narrow
Hepatotoxicity


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
83
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Intestinal varices
Narrow
Intestinal varices haemorrhage
Narrow
Liver and small intestine transplant
Narrow
Liver dialysis
Narrow
Liver disorder
Narrow
Liver injury
Narrow
Liver operation
Narrow
Liver transplant
Narrow
Lupoid hepatic cirrhosis
Narrow
Minimal hepatic encephalopathy
Narrow
Mixed liver injury
Narrow
Nodular regenerative hyperplasia
Narrow
Non-alcoholic fatty liver
Narrow
Non-alcoholic steatohepatitis
Narrow
Non-cirrhotic portal hypertension
Narrow
Oedema due to hepatic disease
Narrow
Oesophageal varices haemorrhage
Narrow
Peripancreatic varices
Narrow
Portal fibrosis
Narrow
Portal hypertension
Narrow
Portal hypertensive colopathy
Narrow
Portal hypertensive enteropathy
Narrow
Portal hypertensive gastropathy


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
84
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Portal vein cavernous transformation
Narrow
Portal vein dilatation
Narrow
Portopulmonary hypertension
Narrow
Renal and liver transplant
Narrow
Retrograde portal vein flow
Narrow
Reye's syndrome
Narrow
Reynold's syndrome
Narrow
Splenic varices
Narrow
Splenic varices haemorrhage
Narrow
Steatohepatitis
Narrow
Subacute hepatic failure
Narrow
Varices oesophageal
Narrow
Varicose veins of abdominal wall
Narrow
White nipple sign
Broad
Anorectal varices
Broad
Anorectal varices haemorrhage
Broad
Intrahepatic portal hepatic venous fistula
Broad
Peritoneovenous shunt
Broad
Portal shunt
Broad
Portal shunt procedure
Broad
Small-for-size liver syndrome
Broad
Spider naevus
Broad
Splenorenal shunt


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
85
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Broad
Splenorenal shunt procedure
Broad
Spontaneous intrahepatic portosystemic venous shunt
Broad
Stomal varices
Narrow
Acute graft versus host disease in liver
Narrow
Allergic hepatitis
Narrow
Autoimmune hepatitis
Narrow
Chronic graft versus host disease in liver
Narrow
Chronic hepatitis
Narrow
Graft versus host disease in liver
Narrow
Hepatitis
Narrow
Hepatitis acute
Narrow
Hepatitis cholestatic
Narrow
Hepatitis chronic active
Narrow
Hepatitis chronic persistent
Narrow
Hepatitis fulminant
Narrow
Hepatitis toxic
Narrow
Ischaemic hepatitis
Narrow
Lupus hepatitis
Narrow
Non-alcoholic steatohepatitis
Narrow
Radiation hepatitis
Narrow
Steatohepatitis
Broad
Granulomatous liver disease
Broad
Liver sarcoidosis


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
86
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Broad
Portal tract inflammation
Narrow
Benign hepatic neoplasm
Narrow
Benign hepatobiliary neoplasm
Narrow
Focal nodular hyperplasia
Narrow
Haemangioma of liver
Narrow
Haemorrhagic hepatic cyst
Narrow
Hepatic adenoma
Narrow
Hepatic cyst
Narrow
Hepatic cyst ruptured
Narrow
Hepatic haemangioma rupture
Narrow
Hepatic hamartoma
Narrow
Hepatobiliary cyst
Narrow
Cholangiosarcoma
Narrow
Hepatic angiosarcoma
Narrow
Hepatic cancer
Narrow
Hepatic cancer metastatic
Narrow
Hepatic cancer recurrent
Narrow
Hepatic cancer stage I
Narrow
Hepatic cancer stage II
Narrow
Hepatic cancer stage III
Narrow
Hepatic cancer stage IV
Narrow
Hepatobiliary cancer
Narrow
Hepatobiliary cancer in situ


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
87
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Hepatoblastoma
Narrow
Hepatoblastoma recurrent
Narrow
Hepatocellular carcinoma
Narrow
Liver carcinoma ruptured
Narrow
Mixed hepatocellular cholangiocarcinoma
Broad
Liver ablation
Narrow
Hepatic neoplasm
Narrow
Hepatobiliary neoplasm
Narrow
Alanine aminotransferase abnormal
Narrow
Alanine aminotransferase increased
Narrow
Ammonia abnormal
Narrow
Ammonia increased
Narrow
Ascites
Narrow
Aspartate aminotransferase abnormal
Narrow
Aspartate aminotransferase increased
Narrow
Bacterascites
Narrow
Bile output abnormal
Narrow
Bile output decreased
Narrow
Biliary ascites
Narrow
Bilirubin conjugated abnormal
Narrow
Bilirubin conjugated increased
Narrow
Bilirubin urine present
Narrow
Biopsy liver abnormal


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
88
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Blood bilirubin abnormal
Narrow
Blood bilirubin increased
Narrow
Blood bilirubin unconjugated increased
Narrow
Bromosulphthalein test abnormal
Narrow
Child-Pugh-Turcotte score abnormal
Narrow
Child-Pugh-Turcotte score increased
Narrow
Computerised tomogram liver
Narrow
Computerised tomogram liver abnormal
Narrow
Foetor hepaticus
Narrow
Galactose elimination capacity test abnormal
Narrow
Galactose elimination capacity test decreased
Narrow
Gamma-glutamyltransferase abnormal
Narrow
Gamma-glutamyltransferase increased
Narrow
Guanase increased
Narrow
Hepaplastin abnormal
Narrow
Hepaplastin decreased
Narrow
Hepatic artery flow decreased
Narrow
Hepatic congestion
Narrow
Hepatic enzyme abnormal
Narrow
Hepatic enzyme decreased
Narrow
Hepatic enzyme increased
Narrow
Hepatic function abnormal
Narrow
Hepatic hydrothorax


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
89
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Hepatic hypertrophy
Narrow
Hepatic mass
Narrow
Hepatic pain
Narrow
Hepatic sequestration
Narrow
Hepatic vascular resistance increased
Narrow
Hepatobiliary scan abnormal
Narrow
Hepatomegaly
Narrow
Hepatosplenomegaly
Narrow
Hyperammonaemia
Narrow
Hyperbilirubinaemia
Narrow
Hypercholia
Narrow
Hypertransaminasaemia
Narrow
Kayser-Fleischer ring
Narrow
Liver function test abnormal
Narrow
Liver function test decreased
Narrow
Liver function test increased
Narrow
Liver induration
Narrow
Liver palpable
Narrow
Liver scan abnormal
Narrow
Liver tenderness
Narrow
Mitochondrial aspartate aminotransferase increased
Narrow
Molar ratio of total branched-chain amino acid to 
tyrosine
Narrow
Nuclear magnetic resonance imaging liver abnormal


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
90
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Oedema due to hepatic disease
Narrow
Perihepatic discomfort
Narrow
Retrograde portal vein flow
Narrow
Total bile acids increased
Narrow
Transaminases abnormal
Narrow
Transaminases increased
Narrow
Ultrasound liver abnormal
Narrow
Urine bilirubin increased
Narrow
White nipple sign
Narrow
X-ray hepatobiliary abnormal
Broad
5'nucleotidase increased
Broad
Blood alkaline phosphatase abnormal
Broad
Blood alkaline phosphatase increased
Broad
Blood cholinesterase abnormal
Broad
Blood cholinesterase decreased
Broad
Deficiency of bile secretion
Broad
Glutamate dehydrogenase increased
Broad
Haemorrhagic ascites
Broad
Hepatic fibrosis marker abnormal
Broad
Hepatic fibrosis marker increased
Broad
Hepatic lymphocytic infiltration
Broad
Hypoalbuminaemia
Broad
Leucine aminopeptidase increased


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
91
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Broad
Liver iron concentration abnormal
Broad
Liver iron concentration increased
Broad
Model for end stage liver disease score abnormal
Broad
Model for end stage liver disease score increased
Broad
Periportal oedema
Broad
Peritoneal fluid protein abnormal
Broad
Peritoneal fluid protein decreased
Broad
Peritoneal fluid protein increased
Broad
Pneumobilia
Broad
Portal vein flow decreased
Broad
Portal vein pressure increased
Broad
Retinol binding protein decreased
Broad
Urobilinogen urine decreased
Broad
Urobilinogen urine increased
Narrow
Acquired antithrombin III deficiency
Narrow
Acquired protein S deficiency
Narrow
Anti factor X activity abnormal
Narrow
Anti factor X activity decreased
Narrow
Anti factor X activity increased
Narrow
Antithrombin III decreased
Narrow
Blood fibrinogen abnormal
Narrow
Blood fibrinogen decreased
Narrow
Blood thrombin abnormal


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
92
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Blood thrombin decreased
Narrow
Blood thromboplastin abnormal
Narrow
Blood thromboplastin decreased
Narrow
Coagulation factor decreased
Narrow
Coagulation factor IX level abnormal
Narrow
Coagulation factor IX level decreased
Narrow
Coagulation factor V level abnormal
Narrow
Coagulation factor V level decreased
Narrow
Coagulation factor VII level abnormal
Narrow
Coagulation factor VII level decreased
Narrow
Coagulation factor X level abnormal
Narrow
Coagulation factor X level decreased
Narrow
Hyperfibrinolysis
Narrow
Hypocoagulable state
Narrow
Hypofibrinogenaemia
Narrow
Hypoprothrombinaemia
Narrow
Hypothrombinaemia
Narrow
Hypothromboplastinaemia
Narrow
International normalised ratio abnormal
Narrow
International normalised ratio increased
Narrow
Protein C decreased
Narrow
Protein S abnormal
Narrow
Protein S decreased


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
93
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Prothrombin level abnormal
Narrow
Prothrombin level decreased
Narrow
Prothrombin time abnormal
Narrow
Prothrombin time prolonged
Narrow
Prothrombin time ratio abnormal
Narrow
Prothrombin time ratio increased
Narrow
Thrombin time abnormal
Narrow
Thrombin time prolonged
Hepatic disorders 
specifically reported as 
alcohol-related (SMQ)
Narrow
Alcoholic liver disease
Narrow
Cirrhosis alcoholic
Narrow
Fatty liver alcoholic
Narrow
Hepatic steato-fibrosis
Narrow
Hepatitis alcoholic
Narrow
Zieve syndrome
Liver infections (SMQ)
Narrow
Acute hepatitis B
Narrow
Acute hepatitis C
Narrow
Adenoviral hepatitis
Narrow
Asymptomatic viral hepatitis
Narrow
Chronic hepatitis B
Narrow
Chronic hepatitis C
Narrow
Congenital hepatitis B infection
Narrow
Cytomegalovirus hepatitis


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
94
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
HBV-DNA polymerase increased
Narrow
Hepatic amoebiasis
Narrow
Hepatic candidiasis
Narrow
Hepatic cyst infection
Narrow
Hepatic echinococciasis
Narrow
Hepatic gas gangrene
Narrow
Hepatic infection
Narrow
Hepatic infection bacterial
Narrow
Hepatic infection fungal
Narrow
Hepatic infection helminthic
Narrow
Hepatitis A
Narrow
Hepatitis A antibody abnormal
Narrow
Hepatitis A antibody positive
Narrow
Hepatitis A antigen positive
Narrow
Hepatitis A virus test positive
Narrow
Hepatitis B
Narrow
Hepatitis B antibody abnormal
Narrow
Hepatitis B antibody positive
Narrow
Hepatitis B core antibody positive
Narrow
Hepatitis B core antigen positive
Narrow
Hepatitis B DNA assay positive
Narrow
Hepatitis B DNA increased
Narrow
Hepatitis B e antibody positive


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
95
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Hepatitis B e antigen positive
Narrow
Hepatitis B reactivation
Narrow
Hepatitis B surface antibody positive
Narrow
Hepatitis B surface antigen positive
Narrow
Hepatitis B virus test positive
Narrow
Hepatitis C
Narrow
Hepatitis C antibody positive
Narrow
Hepatitis C core antibody positive
Narrow
Hepatitis C RNA increased
Narrow
Hepatitis C RNA positive
Narrow
Hepatitis C virus test positive
Narrow
Hepatitis D
Narrow
Hepatitis D antibody positive
Narrow
Hepatitis D antigen positive
Narrow
Hepatitis D RNA positive
Narrow
Hepatitis D virus test positive
Narrow
Hepatitis E
Narrow
Hepatitis E antibody abnormal
Narrow
Hepatitis E antibody positive
Narrow
Hepatitis E antigen positive
Narrow
Hepatitis E virus test positive
Narrow
Hepatitis F
Narrow
Hepatitis G


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
96
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Narrow
Hepatitis H
Narrow
Hepatitis infectious mononucleosis
Narrow
Hepatitis mumps
Narrow
Hepatitis non-A non-B
Narrow
Hepatitis non-A non-B non-C
Narrow
Hepatitis post transfusion
Narrow
Hepatitis syphilitic
Narrow
Hepatitis toxoplasmal
Narrow
Hepatitis viral
Narrow
Hepatitis viral test positive
Narrow
Hepatobiliary infection
Narrow
Hepatosplenic abscess
Narrow
Hepatosplenic candidiasis
Narrow
Herpes simplex hepatitis
Narrow
Liver abscess
Narrow
Perinatal HBV infection
Narrow
Schistosomiasis liver
Narrow
Sustained viral response
Narrow
Viral hepatitis carrier
Narrow
Withdrawal hepatitis
Broad
Gianotti-Crosti syndrome
Broad
Portal pyaemia
Broad
Weil's disease


Allergan Confidential
SAP UBR-MD-04
Ubrogepant
97
SMQs under Hepatic disorders 
(SMQ)
SMQ Type
Preferred Term
Pregnancy-related hepatic 
disorders (SMQ)
Narrow
Acute fatty liver of pregnancy
Narrow
Cholestasis of pregnancy