Study to Evaluate the Efficacy and Safety of Erenumab (AM... | NCT02456740

ID	Type	Description	Link
2014-004464-38	EudraCT Number

Study to Evaluate the Efficacy and Safety of Erenumab (AM... | NCT02456740 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. At week 24, participants were re-randomized to receive either erenumab 70 mg or erenumab 140 mg, administered QM at weeks 24, 28, 32, 36, 40, 44, and 48, with actual dose blinded.	Drug: Placebo
Erenumab 70 mg QM	Experimental	Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. At week 24, participants were re-randomized to receive either erenumab 70 mg or erenumab 140 mg, administered QM at weeks 24, 28, 32, 36, 40, 44, and 48, with actual dose blinded.	Drug: Erenumab
Erenumab 140 mg QM	Experimental	Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. At week 24, participants were re-randomized to receive either erenumab 70 mg or erenumab 140 mg, administered QM at weeks 24, 28, 32, 36, 40, 44, and 48, with actual dose blinded.	Drug: Erenumab

Name	Type	Description	Arm Group Labels	Other Names
Erenumab	Drug	Administered by subcutaneous injection once a month	Erenumab 140 mg QM Erenumab 70 mg QM

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Mean Monthly Migraine Days to the Last 3 Months of the Double-blind Treatment Period	A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.	4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days in the Last 3 Months of the Double-blind Treatment Phase	A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura. At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 3 months (mean of months 4, 5 and 6) of the 24-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.

Contacts/Locations Module

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Phoenix	Arizona	85023	United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation
30086681	Background	Buse DC, Lipton RB, Hallstrom Y, Reuter U, Tepper SJ, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. Migraine-related disability, impact, and health-related quality of life among patients with episodic migraine receiving preventive treatment with erenumab. Cephalalgia. 2018 Sep;38(10):1622-1631. doi: 10.1177/0333102418789072. Epub 2018 Aug 7.
	Background	Cheng S, Picard H, Zhang F, Eisele O, Mikol DD. Efficacy and safety of erenumab for migraine prevention: an overview. Japanese Journal of Headache. 2019; 45 : 493-505.
29171821

Label	URL
AmgenTrials clinical trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
FG001	Erenumab 70 mg QM

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Decision by Sponsor		FG0001 subjects FG0011 subjects FG0021 subjects FG0030 subjects FG0040 subjects FG0050 subjects FG0060 subjects FG0070 subjects FG0080 subjects
Withdrawal by Subject		FG00027 subjects FG00128 subjects FG00221 subjects FG0030 subjects FG004
Lost to Follow-up		FG0009 subjects FG0014 subjects FG0025 subjects FG0030 subjects FG004

Active Treatment Phase (Weeks 24 - 52)

Type	Comment	Milestone Data
STARTED	Fourteen participants who completed the DBTP did not continue onto the active treatment phase	FG0000 subjects FG0010 subjects FG0020 subjects FG003138 subjects FG004140 subjects FG005143 subjects FG006140 subjects FG007140 subjects FG008144 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG003124 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG00314 subjects FG004

Type	Comment	Reasons
Protocol Specified Criteria		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
BG001	Erenumab 70 mg QM	Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
BG002	Erenumab 140 mg QM	Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG000319 ParticipantsBG001317 ParticipantsBG002319 ParticipantsBG003

Age, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000319 ParticipantsBG001317 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000319 ParticipantsBG001317 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000319 ParticipantsBG001317 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000319 ParticipantsBG001317 ParticipantsBG002

Region

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000319 ParticipantsBG001317 ParticipantsBG002

Treatment Status with Migraine Prophylactic Medication

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000319 ParticipantsBG001317 ParticipantsBG002

Monthly Migraine Days

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase.

Participants with non-missing values

Mean

Standard Deviation

migraine days/month

Title	Denominators	Categories
	ParticipantsBG000318 ParticipantsBG001316

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Mean Monthly Migraine Days to the Last 3 Months of the Double-blind Treatment Period

The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.

The analysis was conducted in the efficacy analysis set which includes participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in monthly migraine days in the double-blind treatment phase.

Posted

Least Squares Mean

Standard Error

migraine days / month

4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

ID	Title	Description
OG000	Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
OG001	Erenumab 70 mg QM	Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
OG002	Erenumab 140 mg QM	Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.

Units	Counts
Participants	OG000316 OG001312 OG002318

Title

Denominators

Categories

Title	Measurements
	OG000-1.83± 0.18 OG001-3.23± 0.18 OG002-3.67± 0.18

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The primary endpoint was analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.	Generalized Linear Mixed Model		< 0.001		LS Mean Difference	-1.40			2-Sided	95	-1.88	-0.92					Superiority	The primary endpoint was tested independently for each erenumab dose at an alpha level of 0.04 for 70 mg and of 0.01 for 140 mg to maintain the type 1 error rate at an alpha level of 0.05.

Secondary

Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days in the Last 3 Months of the Double-blind Treatment Phase

At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 3 months (mean of months 4, 5 and 6) of the 24-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.

Posted

Number

percentage of participants

4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

ID	Title	Description
OG000	Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
OG001	Erenumab 70 mg QM	Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.

Secondary

Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days to the Last 3 Months of the Double-blind Treatment Period

Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.

The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment phase - the number of migraine-specific treatment days during the 4-week baseline phase.

Posted

Least Squares Mean

Standard Error

Acute migraine-specific med days/mo

4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

ID	Title	Description
OG000	Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
OG001	Erenumab 70 mg QM	Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.

Secondary

Change From Baseline in Mean Monthly Average Physical Impairment Domain Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase

The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.

Change from baseline was calculated as (mean monthly average physical impairment scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly average physical impairment scores as measured by the MPFID).

The analysis was conducted in the efficacy analysis set including participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in MPFID average physical impairment domain score in the double-blind treatment phase.

Posted

Least Squares Mean

Standard Error

units on a scale

4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

ID	Title	Description
OG000	Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.

Secondary

Change From Baseline in Mean Monthly Average Impact on Everyday Activities Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase

Change from baseline was calculated as (mean monthly impact on everyday activities scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly impact on everyday activities scores as measured by the MPFID).

The analysis was conducted in the efficacy analysis set including participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in MPFID average impact on everyday activities domain score in the double-blind treatment phase.

Posted

Least Squares Mean

Standard Error

units on a scale

4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

ID	Title	Description
OG000	Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-blind Treatment Phase: Placebo	Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	7	319	53	319
EG001	Double-blind Treatment Phase: Erenumab 70 mg	Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	8	314	53	314
EG002	Double-blind Treatment Phase: Erenumab 140 mg	Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	8	319	54	319
EG003	Active Treatment Phase: Erenumab 70 mg	Participants received erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	14	421	83	421
EG004	Active Treatment Phase: Erenumab 140 mg	Participants received erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	14	424	63	424

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pericarditis	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG0030 affected421 at risk EG0041 affected424 at risk
Arrhythmogenic right ventricular dysplasia	Congenital, familial and genetic disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Idiopathic orbital inflammation	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected319 at risk EG0011 affected314 at risk EG0021 affected319 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0012 affected314 at risk EG0020 affected319 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Appendicitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Erysipelas	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Kidney infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Postoperative abscess	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0011 affected314 at risk EG0020 affected319 at risk EG003
Sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Vestibular neuronitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Post-traumatic neck syndrome	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0011 affected314 at risk EG0020 affected319 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0011 affected314 at risk EG0020 affected319 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Breast fibroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Prolactin-producing pituitary tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Cerebral venous thrombosis	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Idiopathic intracranial hypertension	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Migraine	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0011 affected314 at risk EG0020 affected319 at risk EG003
Migraine with aura	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Syncope	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0021 affected319 at risk EG003
Toxic encephalopathy	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Depression	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Breast cyst	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Endometriosis	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0011 affected314 at risk EG0020 affected319 at risk EG003
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected319 at risk EG0010 affected314 at risk EG0020 affected319 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG00019 affected319 at risk EG00121 affected314 at risk EG00215 affected319 at risk EG00325 affected421 at risk EG00419 affected424 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG00034 affected319 at risk EG00132 affected314 at risk EG00239 affected319 at risk EG003

Ancestor Terms

ID	Term
D051270	Headache Disorders, Primary
D020773	Headache Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

Title	Measurements
American Indian or Alaska Native	BG0002 BG0010 BG0021 BG0033
Asian	BG0008 BG0015 BG0024 BG00317
Black or African American	BG00024 BG00124 BG00218 BG00366
Multiple	BG0002 BG0011 BG0020 BG0033
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0021 BG0031
White	BG000277 BG001281 BG002293 BG003851
Other	BG0006 BG0016 BG0022 BG00314

Title	Measurements
Current migraine prophylactic treatment	BG0008 BG0016 BG0027 BG00321
Prior migraine prophylactic treatment only	BG000119 BG001119 BG002120 BG003358
No prior / current migraine prophylactic treatment	BG000192 BG001192 BG002192 BG003576

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analyzed using a Cochran-Mantel-Haenszel test, stratified by the randomization stratification factors (region and prior/current treatment with migraine prophylactic medication).	Cochran-Mantel-Haenszel		< 0.001		Odds Ratio (OR)	2.13			2-Sided	95	1.52	2.98					Superiority	If the primary endpoint was statistically significant for the erenumab 70 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.04.
OG000 OG002	Analyzed using a Cochran-Mantel-Haenszel test, stratified by the randomization stratification factors (region and prior/current treatment with migraine prophylactic medication).	Cochran-Mantel-Haenszel		< 0.001		Odds Ratio (OR)	2.81			2-Sided	95	2.01	3.94					Superiority	If the primary endpoint was statistically significant for the erenumab 140 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.01.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.	Generalized Linear Mixed Model		< 0.001		LS Mean Difference	-0.94			2-Sided	95	-1.23	-0.64					Superiority	If the primary endpoint was statistically significant for the erenumab 70 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.04.
OG000 OG002	Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, (stratification factors region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.	Generalized Linear Mixed Model		< 0.001		LS Mean Difference	-1.42			2-Sided	95	-1.71	-1.12					Superiority	If the primary endpoint was statistically significant for the erenumab 140 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.01.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.	Generalized Linear Mixed Model		< 0.001		LS Mean Difference	-2.43			2-Sided	95	-3.51	-1.35					Superiority	If the first tier secondary endpoints were statistically significant for both erenumab doses the erenumab 140 mg group for the 2 remaining MPFID secondary endpoints was tested using the Hochberg method at a level of 0.05; If only the erenumab 70 mg group or 140 mg group showed statistical significance for the first tier secondary endpoints then the erenumab 140 group for the 2 remaining MPFID secondary endpoints was tested for significance at a level of either 0.04 or 0.01 respectively.
OG000 OG001	Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.	Generalized Linear Mixed Model		< 0.001		LS Mean Difference	-1.86			2-Sided	95	-2.95	-0.77					Superiority	If the erenumab 140 mg group for both remaining MPFID secondary endpoints were statistically significant, then the erenumab 70 mg group for the two remaining MPFID secondary endpoints was tested for significance using the Hochberg method with the same alpha level carried over from 140 mg group.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.	Generalized Linear Mixed Model		< 0.001		LS Mean Difference	-2.57			2-Sided	95	-3.62	-1.51					Superiority	If the first tier secondary endpoints were statistically significant for both erenumab doses the erenumab 140 mg group for the 2 remaining MPFID secondary endpoints was tested using the Hochberg method at a level of 0.05; If only the erenumab 70 mg group or 140 mg group showed statistical significance for the first tier secondary endpoints then the erenumab 140 group for the 2 remaining MPFID secondary endpoints was tested for significance at a level of either 0.04 or 0.01 respectively.
OG000 OG001	Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.	Generalized Linear Mixed Model		< 0.001		LS Mean Difference	-2.22			2-Sided	95	-3.28	-1.16					Superiority	If the erenumab 140 mg group for both remaining MPFID secondary endpoints were statistically significant, then the erenumab 70 mg group for the two remaining MPFID secondary endpoints was tested for significance using the Hochberg method with the same alpha level carried over from 140 mg group.