A Safety and Efficacy Study to Evaluate AMG 334 in Migraine Prevention

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02630459
• Collaborator: (none)
• Enrollment: 475
• Locations: 44
• Arms: 7
• Actual Duration (Months): 40.9
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Randomized, double-blind, placebo-controlled, parallel-group, multicenter study followed by an open-label treatment phase (OLTP). To evaluate the effect of erenumab (AMG 334) compared to placebo on the change from baseline in monthly migraine days.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Placebo; Drug: Erenumab; Drug: Erenumab	Phase 2

Detailed Description

This is a Phase 2, randomized, double-blind, placebo-controlled study in participants with episodic migraine. The study's double blind treatment phase (DBTP) is designed to evaluate if treatment with erenumab once a month for 6 months compared with placebo is effective in reducing the mean monthly migraine days. Additionally, this study will continue to evaluate the efficacy and safety of erenumab during the OLTP where participants will continue to receive active treatment monthly.

The study also includes a clinical home use (CHU) sub-study to assess a participant's ability to self-administer 140 mg of erenumab. Participants will be randomized 1:1 to use either 2 pre-filled 70 mg/mL autoinjector (AI)/pens or 1 pre-filled 140 mg/mL AI/pen. Participation in the substudy is optional, and no additional samples will be collected for the sub-study.

After implementation of Protocol Amendment 2, the dose of erenumab in the OLTP increased from 70 mg to 140 mg QM. Participants who had already completed week 48 remain on 70 mg QM, participants not yet starting the OLTP, or not yet completing the week 48 visit receive erenumab 140 mg QM for the remainder of the OLTP.

Study Design

• Study Type: Interventional
• Actual Enrollment: 475 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
• Actual Study Start Date: Jan 6, 2016
• Actual Primary Completion Date: Sep 25, 2017
• Actual Study Completion Date: Jun 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Double Blind Treatment Phase (DBTP): Placebo Participants received placebo by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.	Drug: Placebo; placebo via subcutaneous injection
Experimental: DBTP: Erenumab 28 mg QM Participants received erenumab 28 mg by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.	Drug: Erenumab; erenumab via subcutaneous injection; Other Names: AMG 334, Aimovig™
Experimental: DBTP: Erenumab 70 mg QM Participants received erenumab 70 mg by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.	Drug: Erenumab; erenumab via subcutaneous injection; Other Names: AMG 334, Aimovig™
Experimental: DBTP: Erenumab 140 mg QM Participants received erenumab 140 mg by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.	Drug: Erenumab; erenumab via subcutaneous injection; Other Names: AMG 334, Aimovig™
Experimental: Open-Label Treatment Phase (OLTP): Erenumab 70-140 mg QM Participants received an erenumab dose of 70 and/or 140 mg QM SC (depending on the participant's visit completion status after Institutional Review Board [IRB] approval of Protocol Amendment 2) in the OLTP for a total of 76 weeks.	Drug: Erenumab; erenumab via subcutaneous injection; Other Names: AMG 334, Aimovig™
Experimental: CHU Sub-Study: Two 70 mg/mL AI/pens A subset of participants in the OLTP randomized to self administer erenumab via two 70 mg/mL autoinjector (AI)/pens on day 29 and day 57 of the CHU Sub-Study	Drug: Erenumab; erenumab via autoinjector (AI)/pen; Other Names: AMG 334, Aimovig™
Experimental: CHU Sub-Study: One 140 mg/mL AI/pen A subset of participants in the OLTP randomized to self administer erenumab via one 140 mg/mL AI/pen on day 29 and day 57 of the CHU Sub-Study	Drug: Erenumab; erenumab via autoinjector (AI)/pen; Other Names: AMG 334, Aimovig™

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 [4-week baseline phase and months 4, 5 and 6 of DBTP.]

   A migraine day was defined as 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 a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. Change from baseline was calculated using the mean monthly migraine days from months 4, 5 and 6 of the DBTP minus the number of migraine days during the 4-week baseline phase. Least squares (LS) mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (current, prior only, or no prior/current treatment), and baseline value as covariates.

2. CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) [CHU day 29 (week 4) and day 57 (week 8)]

   On CHU day 29 and day 57, site staff interviewed sub-study participants and asked if they administered a full, partial, or no dose of erenumab (after explaining that a full dose means that the entire volume of the AI/pen was injected) and documented the participant's response in the electronic case report form. Data presented are the percentage of participants who reported "full administration," "not full administration," or "discontinued investigational product (ie, no dose)." (Day 1 of the CHU substudy occurred at any OLTP study visit [up to week 88] as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.)

Secondary Outcome Measures

1. Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 [4-week baseline phase and months 4, 5 and 6 of DBTP.]

   A migraine day was defined as 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 a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. At least a 50% reduction from baseline in monthly migraine days was determined if: (mean monthly migraine days over the last three months of the DBTP minus baseline monthly migraine days) * 100 / baseline monthly migraine days, was less than or equal to -50%.

2. Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6 [4-week baseline phase and months 4, 5 and 6 of DBTP.]

   An acute migraine-specific medication treatment day was defined as any calendar day during which the participant took a migraine-specific medication (ie, triptan or ergotamine-derivatives). The change from baseline was calculated using the mean monthly acute migraine-specific medication treatment days over the last three months (months 4, 5 and 6) of the DBTP minus the baseline monthly acute migraine-specific medication treatment days. LS mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment), and baseline value as covariates.

3. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP [From first dose of IP up to week 24]

   An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. A serious adverse event (SAE) is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).

4. Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP [From first dose of IP in the OLTP (week 24) through the end of the OLTP (week 100) plus 12 weeks]

   An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).

5. Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study [CHU sub-study day 1 through day 85 (end of CHU sub-study). Day 1 of the CHU substudy occurred at any OLTP study visit (up to week 88) as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.]

   An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death). TEAEs leading to discontinuation of IP are TEAEs leading to complete discontinuation of erenumab regardless of CHU IP or parent study IP.

6. Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP [From the first dose of study IP through the end of the DBTP (up to week 24)]

   Post-baseline is defined as any assessment done after the first dose of IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.

7. Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP [From the first dose of OLTP IP (week 24) through the end of the OLTP (up to week 100)]

   Post-baseline is defined as any assessment done after the first dose of OLTP IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.

8. Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP [Baseline (last assessment prior to first dose of IP), week 24]

   Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 24 (Wk24) are presented.

9. Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP [Pre-OLTP Baseline (last assessment prior to first dose of IP in OLTP), week 100]

   Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 100 (Wk100) are presented.

10. Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab [Baseline (first dose of erenumab) up to end of study (week 100) plus 12 weeks]

    Data are summarized by the treatment participants received during the double-blind treatment phase. Placebo participants may have received erenumab 70 mg or 140 mg during the OLTP. Baseline is defined as the last antibody assessment on or prior to the first dose of erenumab. Transient binding/neutralizing antibody responses are defined as a negative (neg) result at the participant's last timepoint tested among participants who developed binding/neutralizing antibodies post-baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria to be assessed prior to entering the subject into the initial screening and/or baseline phase:

• Provided informed consent prior to initiation of any study-specific activities/procedures

• History of migraine (with or without aura) for ≥ 12 months prior to screening according to the International Headache Society (IHS) Classification The International Classification of Headache Disorders (ICHD)-3 (Headache Classification Committee of the IHS, 2013),

• Migraine frequency: ≥ 4 and < 15 migraine days per month on average across the 3 months prior to screening,

• Headache frequency: < 15 headache days per month on average across the 3 months prior to screening.

Inclusion Criteria to be assessed during the baseline phase and confirmed prior to randomizing the subject into the double-blind treatment phase:

• Demonstrated at least 80% compliance with the electronic Diary (eDiary),

• Migraine frequency: ≥ 4 and < 15 migraine days during the baseline phase based on the eDiary calculations,

• Headache frequency: < 15 headache days during the baseline phase based on the eDiary calculations.

Inclusion Criteria for the Clinical Home Use (CHU) Substudy:

• Subjects must have provided informed consent for the substudy. Subjects enrolling in the CHU substudy must have received open-label 140 mg erenumab for at least 1 dose.

Exclusion Criteria:

• Older than 50 years of age at migraine onset,

• History of cluster headache or hemiplegic migraine headache,

• Unable to differentiate migraine from other headaches,

• No therapeutic response with > 2 of the following 7 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial: Category 1: Divalproex sodium, sodium valproate, Category 2: Topiramate, Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, propranolol, timolol), Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, protriptyline),Category 5: Serotonin-norepinephrine reuptake inhibitors (for example: venlafaxine, desvenlafaxine, duloxetine, milnacipran), Category 6: Flunarizine, verapamil, lomerizine, Category 7: Lisinopril, candesartan,

• Used a prohibited medication, device or procedure within 2 months prior to the start of the baseline phase or during the baseline phase,

• Received botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline phase or during the baseline phase,

• Taken the following for any indication in any month during the 2 months prior to the start of the baseline phase: Ergotamines or triptans on ≥ 10 days per month, or Simple analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on ≥ 15 days per month, or Opioid- or butalbital-containing analgesics on ≥ 4 days per month,

• Anticipated to require any excluded medication, device or procedure during the study,

• Active chronic pain syndromes (such as fibromyalgia and chronic pelvic pain),

• History of major psychiatric disorder (such as schizophrenia and bipolar disorder), or current evidence of depression based on a Beck Depression Inventory (BDI)-II total score > 19 at screening. Subjects with anxiety disorder and/or major depressive disorder are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Subjects must have been on a stable dose within the 3 months prior to the start of the baseline phase,

• History of seizure disorder or other significant neurological conditions other than migraine. Note: A single childhood febrile seizure is not exclusionary,

• Malignancy within the 5 years prior to screening, except non melanoma skin cancers, cervical or breast ductal carcinoma in situ,

• Human immunodeficiency virus (HIV) infection by history,

• Hepatic disease by history, or total bilirubin (TBL) ≥ 2.0 x upper limit of normal (ULN) or alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 3.0 x ULN, as assessed by the central laboratory at initial screening, or evidence of acute or chronic hepatitis B or hepatitis C virus. Hepatitis status will be evaluated by testing for hepatitis B surface antigen (HepBsAg), total hepatitis B core antibody (HepBcAb) and hepatitis C antibody by the central laboratory at initial screening. Polymerase chain reaction (PCR) should be performed to confirm active disease only if total HepBcAb is positive and HepBsAg is negative or if C antibody is positive,

• Myocardial infarction, stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening,

• History or evidence of any other unstable or clinically significant medical condition that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion,

• Subject has any clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation,

• The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior or endorsing items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessed at screening,

• Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records, patient self-report, or positive urine drug test performed during screening (with the exception of prescribed medications such as opioids or barbiturates),

• Pregnant or breastfeeding, or is a female expecting to conceive during the study, including through 16 weeks after the last dose of investigational product,

• Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product through 16 weeks after the last dose of investigational product,

• Currently receiving treatment in another investigational device or drug study, or less than 90 days prior to screening since ending treatment on another investigational device or drug study(-ies),

• Known sensitivity to any component of the investigational product (Refer to the Investigational Product Instruction Manual [IPIM] for details),

• Previously randomized into an erenumab study,

• Member of investigational site staff or relative of the investigator,

• Unlikely to be able to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, independent completion of eDiary items) to the best of the subject's and investigator's knowledge.

Exclusion Criteria for the CHU Substudy:

• Unreliability as a study participant based on the investigator's (or designee's) knowledge of the subject (eg, unwillingness to adhere to the protocol, unwilling to self-inject using an autoinjector (AI)/pen after review of the Instructions for Use). Subjects receiving erenumab 70 mg in the open-label phase are not eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Kamogawa-shi	Chiba	Japan	296-0041
2	Research Site	Saijo-shi	Ehime	Japan	793-0030
3	Research Site	Ota-shi	Gunma	Japan	373-8585
4	Research Site	Hiroshima-shi	Hiroshima	Japan	730-8518
5	Research Site	Sapporo-shi	Hokkaido	Japan	060-0004
6	Research Site	Sapporo-shi	Hokkaido	Japan	060-8570
7	Research Site	Sapporo-shi	Hokkaido	Japan	063-0005
8	Research Site	Kobe-shi	Hyogo	Japan	658-0064
9	Research Site	Tsukuba-shi	Ibaraki	Japan	305-8576
10	Research Site	Kahoku-gun	Ishikawa	Japan	929-0342
11	Research Site	Morioka-shi	Iwate	Japan	020-8505
12	Research Site	Kagoshima-shi	Kagoshima	Japan	892-0844
13	Research Site	Kawasaki-shi	Kanagawa	Japan	211-8533
14	Research Site	Kawasaki-shi	Kanagawa	Japan	211-8588
15	Research Site	Kawasaki-shi	Kanagawa	Japan	216-8511
16	Research Site	Kumamoto-shi	Kumamoto	Japan	861-2101
17	Research Site	Kumamoto-shi	Kumamoto	Japan	862-8505
18	Research Site	Kyoto-shi	Kyoto	Japan	600-8811
19	Research Site	Sendai-shi	Miyagi	Japan	982-0014
20	Research Site	Osaka-shi	Osaka	Japan	556-0017
21	Research Site	Osakasayama-shi	Osaka	Japan	589-8511
22	Research Site	Toyonaka-shi	Osaka	Japan	560-0012
23	Research Site	Saga-shi	Saga	Japan	840-0806
24	Research Site	Iruma-gun	Saitama	Japan	350-0495
25	Research Site	Saitama-shi	Saitama	Japan	338-8577
26	Research Site	Tokorozawa-shi	Saitama	Japan	359-1141
27	Research Site	Shizuoka-shi	Shizuoka	Japan	420-0853
28	Research Site	Shimotsuga-gun	Tochigi	Japan	321-0293
29	Research Site	Bunkyo-ku	Tokyo	Japan	113-8431
30	Research Site	Bunkyo-ku	Tokyo	Japan	113-8603
31	Research Site	Chofu-shi	Tokyo	Japan	182-0006
32	Research Site	Chuo-ku	Tokyo	Japan	104-8560
33	Research Site	Hachioji-shi	Tokyo	Japan	192-0032
34	Research Site	Minato-ku	Tokyo	Japan	106-6106
35	Research Site	Minato-ku	Tokyo	Japan	108-8642
36	Research Site	Shibuya-ku	Tokyo	Japan	151-0051
37	Research Site	Shinjuku-ku	Tokyo	Japan	160-0017
38	Research Site	Shinjuku-ku	Tokyo	Japan	160-8582
39	Research Site	Yonago-city	Tottori	Japan	683-8504
40	Research Site	Toyama-shi	Toyama	Japan	930-0194
41	Research Site	Toyama-shi	Toyama	Japan	930-0803
42	Research Site	Hofu-shi	Yamaguchi	Japan	747-0802
43	Research Site	Yamaguchi-shi	Yamaguchi	Japan	754-0002
44	Research Site	Kai-shi	Yamanashi	Japan	400-0124

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

• Study Protocol - Jun 5, 2017
• Statistical Analysis Plan - Feb 14, 2016

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Lenz R, Wang Y, Cheng S, Hirama T, Mikol DD. A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults. Headache. 2019 Nov;59(10):1731-1742. doi: 10.1111/head.13652. Epub 2019 Oct 14.
• Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02630459
• Other Study ID Numbers: 20120309
• First Posted: Dec 15, 2015
• Last Update Posted: Apr 28, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Amgen: Migraine Prevention; Headache; Prophylaxis
• Additional relevant MeSH terms: Migraine Disorders; Erenumab; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	The study, initiated on 06 January 2016 at 43 centers in Japan, included a 24-week double-blind treatment phase (DBTP) followed by a 76-week open-label (OL) treatment phase (OLTP). DBTP: participants were randomized 2:1:2:2 to receive placebo, erenumab 28 mg, erenumab 70 mg, or erenumab 140 mg once monthly (QM) subcutaneously (SC).
Pre-assignment Detail	OLTP: participants received erenumab 70 mg and/or 140 mg QM SC (depending on the participant's visit completion status after a protocol amendment). Optional 85-day clinical home use (CHU) sub-study during the OLTP: participants randomized 1:1 to erenumab using two 70 mg/mL or one 140 mg/mL autoinjector (AI)/pen(s).

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM	OLTP: Erenumab 70 mg QM (Initial OL Dose)	OLTP: Erenumab 140 mg QM (Initial OL Dose)	CHU Sub-Study: Two 70 mg/mL AI/Pens	CHU Sub-Study: One 140 mg/mL AI/Pen
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Participants assigned to an initial erenumab dose of 70 mg QM SC in the OLTP. After a protocol amendment, participants who had already completed the week 48 OLTP visit continued to receive OL erenumab 70 mg QM SC for a total of 76 weeks. Participants who had not yet completed the OLTP week 48 visit and were already receiving OL erenumab 70 mg QM SC increased their dose to erenumab 140 mg QM SC, continued until the week 100 visit for a total OLTP duration of 76 weeks.	Participants assigned to an initial erenumab dose of 140 mg QM SC in the OLTP. After a protocol amendment, participants who had not yet completed the DBTP and were not yet in the OLTP received an initial dose of erenumab 140 mg QM SC upon entering the OLTP, and continued receiving OL erenumab 140 mg QM SC for 76 weeks.	A subset of participants in the OLTP randomized to self-administer erenumab via two 70 mg/mL AI/pens on CHU sub-study day 1, day 29 and day 57.	A subset of participants in the OLTP randomized to self-administer erenumab via one 140 mg/mL AI/pen on CHU sub-study day 1, day 29 and day 57.
Period Title: Double-Blind Treatment Phase (DBTP)
STARTED	136	67	135	137	0	0	0	0
Received Investigational Product (IP)	136	66	135	137	0	0	0	0
COMPLETED	133	65	130	134	0	0	0	0
NOT COMPLETED	3	2	5	3	0	0	0	0
Period Title: Double-Blind Treatment Phase (DBTP)
STARTED	0	0	0	0	386	73	0	0
Received Only 70 mg in OLTP	0	0	0	0	270	0	0	0
Received Only 140 mg in OLTP	0	0	0	0	0	73	0	0
Received Both 70 mg and 140 mg in OLTP	0	0	0	0	116	0	0	0
COMPLETED	0	0	0	0	357	69	0	0
NOT COMPLETED	0	0	0	0	29	4	0	0
Period Title: Double-Blind Treatment Phase (DBTP)
STARTED	0	0	0	0	0	0	24	25
COMPLETED	0	0	0	0	0	0	24	25
NOT COMPLETED	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM	Total
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Total of all reporting groups
Overall Participants	136	67	135	137	475
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.7 (9.1)	42.8 (6.9)	43.8 (9.0)	45.0 (8.3)	44.0 (8.6)
Sex: Female, Male (Count of Participants)
Female	118 86.8%	55 82.1%	115 85.2%	112 81.8%	400 84.2%
Male	18 13.2%	12 17.9%	20 14.8%	25 18.2%	75 15.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	136 100%	67 100%	135 100%	137 100%	475 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	136 100%	67 100%	135 100%	137 100%	475 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Monthly Migraine Days at Baseline (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	7.67 (2.34)	7.68 (2.14)	7.84 (2.31)	8.14 (2.43)	7.86 (2.33)
Treatment Status with Migraine Prophylactic Medication (Count of Participants)
Current treatment	14 10.3%	7 10.4%	13 9.6%	15 10.9%	49 10.3%
Prior treatment only	75 55.1%	38 56.7%	75 55.6%	75 54.7%	263 55.4%
No prior or current treatment	47 34.6%	22 32.8%	47 34.8%	47 34.3%	163 34.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6
Description	A migraine day was defined as 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 a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. Change from baseline was calculated using the mean monthly migraine days from months 4, 5 and 6 of the DBTP minus the number of migraine days during the 4-week baseline phase. Least squares (LS) mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (current, prior only, or no prior/current treatment), and baseline value as covariates.
Time Frame	4-week baseline phase and months 4, 5 and 6 of DBTP.

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: Participants who received at least 1 dose of the investigational product (IP) and had at least 1 change from baseline measurement in monthly migraine days during the DBTP.

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.
Measure Participants	136	66	135	136
Least Squares Mean (95% Confidence Interval) [Days]	0.06	-1.19	-2.25	-1.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 140 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structure
	Type of Statistical Test	Superiority
	Comments	To maintain a family-wise type I error at 0.05, the pairwise comparisons were tested in a sequential testing procedure in the order of erenumab 140 mg QM vs placebo, erenumab 70 mg QM vs placebo and erenumab 28 mg QM vs placebo. The lower dose group was tested only when the higher dose group was considered statistically significant.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-values for pairwise comparisons were nominal and without multiplicity adjustment.
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.89
	Confidence Interval	(2-Sided) 95%; -2.58 to -1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DPTP: Erenumab 70 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structure
	Type of Statistical Test	Superiority
	Comments	To maintain a family-wise type I error at 0.05, the pairwise comparisons were tested in a sequential testing procedure in the order of erenumab 140 mg QM vs placebo, erenumab 70 mg QM vs placebo and erenumab 28 mg QM vs placebo. The lower dose group was tested only when the higher dose group was considered statistically significant.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-values for pairwise comparisons were nominal and without multiplicity adjustment.
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.31
	Confidence Interval	(2-Sided) 95%; -3.00 to -1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structure
	Type of Statistical Test	Superiority
	Comments	To maintain a family-wise type I error at 0.05, the pairwise comparisons were tested in a sequential testing procedure in the order of erenumab 140 mg QM vs placebo, erenumab 70 mg QM vs placebo and erenumab 28 mg QM vs placebo. The lower dose group was tested only when the higher dose group was considered statistically significant.
Statistical Test of Hypothesis	p-Value	0.004
	Comments	P-values for pairwise comparisons were nominal and without multiplicity adjustment.
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.25
	Confidence Interval	(2-Sided) 95%; -2.10 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8)
Description	On CHU day 29 and day 57, site staff interviewed sub-study participants and asked if they administered a full, partial, or no dose of erenumab (after explaining that a full dose means that the entire volume of the AI/pen was injected) and documented the participant's response in the electronic case report form. Data presented are the percentage of participants who reported "full administration," "not full administration," or "discontinued investigational product (ie, no dose)." (Day 1 of the CHU substudy occurred at any OLTP study visit [up to week 88] as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.)
Time Frame	CHU day 29 (week 4) and day 57 (week 8)

Outcome Measure Data

Analysis Population Description

CHU Sub-Study Analysis Set: all participants randomized into the CHU substudy who received at least one dose of CHU investigational product (IP).

Arm/Group Title	CHU Sub-Study: Two 70 mg/mL AI/Pens	CHU Sub-Study: One 140 mg/mL AI/Pen
Arm/Group Description	A subset of participants in the OLTP randomized to self-administer erenumab via two 70 mg/mL AI/pens on CHU sub-study day 1, day 29 and day 57.	A subset of participants in the OLTP randomized to self-administer erenumab via one 140 mg/mL AI/pen on CHU sub-study day 1, day 29 and day 57.
Measure Participants	24	25
Week 4: Full Administration	100.0 73.5%	100.0 149.3%
Week 4: Not Full Administration	0.0 0%	0.0 0%
Week 4: Discontinued Investigational Product	0.0 0%	0.0 0%
Week 8: Full Administration	100.0 73.5%	100.0 149.3%
Week 8: Not Full Administration	0.0 0%	0.0 0%
Week 8: Discontinued Investigational Product	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	Week 4: Full Administration
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -13.3 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference was calculated using the Newcombe hybrid score method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	Week 4: Not Full Administration
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -13.8 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference was calculated using the Newcombe hybrid score method.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	Week 4: Discontinued Investigational Product
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -13.8 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference was calculated using the Newcombe hybrid score method.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	Week 8: Full Administration
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -13.3 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference was calculated using the Newcombe hybrid score method.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	Week 8: Not Full Administration
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -13.8 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference was calculated using the Newcombe hybrid score method.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	Week 8: Discontinued Investigational Product
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -13.8 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference was calculated using the Newcombe hybrid score method.

3. Secondary Outcome

Title	Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6
Description	A migraine day was defined as 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 a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. At least a 50% reduction from baseline in monthly migraine days was determined if: (mean monthly migraine days over the last three months of the DBTP minus baseline monthly migraine days) * 100 / baseline monthly migraine days, was less than or equal to -50%.
Time Frame	4-week baseline phase and months 4, 5 and 6 of DBTP.

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: Participants who received at least 1 dose of IP and had at least 1 change from baseline measurement in monthly migraine days during the DBTP.

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.
Measure Participants	136	66	135	136
Number [Percentage of participants]	7.4 5.4%	19.7 29.4%	28.9 21.4%	27.2 19.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 140 mg QM
	Comments	The common odds ratios and p-values were obtained from a Cochran-Mantel-Haenszel (CMH) test, stratified by stratification factor prior/current treatment with migraine prophylactic medication status.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-values for pairwise comparisons were nominal and obtained from the CMH test using data including placebo and corresponding erenumab dose group only.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Common Odds Ratio
	Estimated Value	4.73
	Confidence Interval	(2-Sided) 95%; 2.24 to 9.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DPTP: Erenumab 70 mg QM
	Comments	The common odds ratios and p-values were obtained from a CMH test, stratified by stratification factor prior/current treatment with migraine prophylactic medication status.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-values for pairwise comparisons were nominal and obtained from the CMH test using data including placebo and corresponding erenumab dose group only.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Common Odds Ratio
	Estimated Value	5.60
	Confidence Interval	(2-Sided) 95%; 2.60 to 12.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	The common odds ratios and p-values were obtained from a CMH test, stratified by stratification factor prior/current treatment with migraine prophylactic medication status.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	P-values for pairwise comparisons were nominal and obtained from the CMH test using data including placebo and corresponding erenumab dose group only.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Common Odds Ratio
	Estimated Value	3.21
	Confidence Interval	(2-Sided) 95%; 1.30 to 7.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6
Description	An acute migraine-specific medication treatment day was defined as any calendar day during which the participant took a migraine-specific medication (ie, triptan or ergotamine-derivatives). The change from baseline was calculated using the mean monthly acute migraine-specific medication treatment days over the last three months (months 4, 5 and 6) of the DBTP minus the baseline monthly acute migraine-specific medication treatment days. LS mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment), and baseline value as covariates.
Time Frame	4-week baseline phase and months 4, 5 and 6 of DBTP.

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: Participants who received at least 1 dose of IP and had at least 1 change from baseline measurement in monthly migraine days during the DBTP.

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.
Measure Participants	136	66	135	136
Least Squares Mean (95% Confidence Interval) [Days]	0.88	-0.19	-1.19	-1.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 140 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structure
	Type of Statistical Test	Superiority
	Comments	To maintain a family-wise type I error at 0.05, the pairwise comparisons were tested in a sequential testing procedure in the order of erenumab 140 mg QM vs placebo, erenumab 70 mg QM vs placebo and erenumab 28 mg QM vs placebo. The lower dose group was tested only when the higher dose group was considered statistically significant.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-values for pairwise comparisons were nominal and without multiplicity adjustment.
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.04
	Confidence Interval	(2-Sided) 95%; -2.63 to -1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DPTP: Erenumab 70 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structure
	Type of Statistical Test	Superiority
	Comments	To maintain a family-wise type I error at 0.05, the pairwise comparisons were tested in a sequential testing procedure in the order of erenumab 140 mg QM vs placebo, erenumab 70 mg QM vs placebo and erenumab 28 mg QM vs placebo. The lower dose group was tested only when the higher dose group was considered statistically significant.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-values for pairwise comparisons were nominal and without multiplicity adjustment.
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.07
	Confidence Interval	(2-Sided) 95%; -2.66 to -1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBTP: Placebo, DBTP: Erenumab 28 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structure
	Type of Statistical Test	Superiority
	Comments	To maintain a family-wise type I error at 0.05, the pairwise comparisons were tested in a sequential testing procedure in the order of erenumab 140 mg QM vs placebo, erenumab 70 mg QM vs placebo and erenumab 28 mg QM vs placebo. The lower dose group was tested only when the higher dose group was considered statistically significant.
Statistical Test of Hypothesis	p-Value	0.004
	Comments	P-values for pairwise comparisons were nominal and without multiplicity adjustment.
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.07
	Confidence Interval	(2-Sided) 95%; -1.80 to -0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP
Description	An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. A serious adverse event (SAE) is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).
Time Frame	From first dose of IP up to week 24

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least one dose of IP in the DBTP.

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.
Measure Participants	136	66	135	137
All TEAEs	92 67.6%	40 59.7%	95 70.4%	95 69.3%
Grade ≥ 2 TEAEs	60 44.1%	33 49.3%	66 48.9%	65 47.4%
Grade ≥ 3 TEAEs	4 2.9%	1 1.5%	3 2.2%	0 0%
Grade ≥ 4 TEAEs	0 0%	0 0%	1 0.7%	0 0%
Serious TEAEs	4 2.9%	1 1.5%	1 0.7%	1 0.7%
TEAEs Leading to Discontinuation of IP	1 0.7%	0 0%	2 1.5%	0 0%
Fatal TEAEs	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP
Description	An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).
Time Frame	From first dose of IP in the OLTP (week 24) through the end of the OLTP (week 100) plus 12 weeks

Outcome Measure Data

Analysis Population Description

Open-Label Treatment Phase Set: all participants receiving at least one dose of IP in the OLTP, by dose received at the time of the event, and overall (total participants in the OLTP).

Arm/Group Title	OLTP: Erenumab 70 mg QM	OLTP: Erenumab 140 mg QM	OLTP: Total
Arm/Group Description	Erenumab 70 mg SC QM in the OLTP (at the time of the event).	Erenumab 140 mg SC QM in the OLTP (at the time of the event).	Participants receiving erenumab 70 mg and/or 140 mg SC QM in the OLTP
Measure Participants	386	189	459
All TEAEs	292 214.7%	173 258.2%	422 312.6%
Grade ≥ 2 TEAEs	238 175%	147 219.4%	358 265.2%
Grade ≥ 3 TEAEs	19 14%	9 13.4%	28 20.7%
Grade ≥ 4 TEAEs	0 0%	0 0%	0 0%
Serious TEAEs	18 13.2%	9 13.4%	27 20%
TEAEs Leading to Discontinuation of IP	4 2.9%	2 3%	6 4.4%
Fatal TEAEs	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study
Description	An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death). TEAEs leading to discontinuation of IP are TEAEs leading to complete discontinuation of erenumab regardless of CHU IP or parent study IP.
Time Frame	CHU sub-study day 1 through day 85 (end of CHU sub-study). Day 1 of the CHU substudy occurred at any OLTP study visit (up to week 88) as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.

Outcome Measure Data

Analysis Population Description

CHU Sub-Study Analysis Set: all participants randomized into the CHU substudy who received at least one dose of CHU IP.

Arm/Group Title	CHU Sub-Study: Two 70 mg/mL AI/Pens	CHU Sub-Study: One 140 mg/mL AI/Pen
Arm/Group Description	A subset of participants in the OLTP randomized to self-administer erenumab via two 70 mg/mL AI/pens on CHU sub-study day 1, day 29 and day 57.	A subset of participants in the OLTP randomized to self-administer erenumab via one 140 mg/mL AI/pen on CHU sub-study day 1, day 29 and day 57.
Measure Participants	24	25
All TEAEs	11 8.1%	14 20.9%
Grade ≥ 2 TEAEs	9 6.6%	9 13.4%
Grade ≥ 3 TEAEs	0 0%	0 0%
Grade ≥ 4 TEAEs	0 0%	0 0%
Serious TEAEs	1 0.7%	0 0%
TEAEs Leading to Discontinuation of IP	0 0%	0 0%
Fatal TEAEs	0 0%	0 0%
Adverse Device Effects	2 1.5%	1 1.5%

8. Secondary Outcome

Title	Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP
Description	Post-baseline is defined as any assessment done after the first dose of IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.
Time Frame	From the first dose of study IP through the end of the DBTP (up to week 24)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least one dose of IP.

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.
Measure Participants	136	66	135	137
Post-Baseline ALT or AST > 3 x ULN	0 0%	0 0%	3 2.2%	1 0.7%
Post-Baseline ALT or AST > 5 x ULN	0 0%	0 0%	0 0%	1 0.7%
Post-Baseline TBL > 1 x ULN	6 4.4%	3 4.5%	4 3%	4 2.9%
Post-Baseline TBL > 1.5 x ULN	0 0%	1 1.5%	0 0%	1 0.7%
Post-Baseline TBL > 2 x ULN	0 0%	0 0%	0 0%	0 0%
Post-Baseline ALP > 1.5 x ULN	0 0%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP
Description	Post-baseline is defined as any assessment done after the first dose of OLTP IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.
Time Frame	From the first dose of OLTP IP (week 24) through the end of the OLTP (up to week 100)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least one dose of OLTP erenumab.

Arm/Group Title	OLTP: 70 mg SC QM (Only)	OLTP: 140 mg SC QM (Only)	OLTP: 70/140 mg SC QM (Both)	OLTP: Total
Arm/Group Description	Participants who received only erenumab 70 mg SC QM in the OLTP	Participants who received only erenumab 140 mg SC QM in the OLTP	Participants who received both erenumab 70 mg and 140 mg SC QM in the OLTP	Participants who received erenumab 70 mg and/or 140 mg SC QM in the OLTP
Measure Participants	270	73	116	459
Post-Baseline ALT or AST > 3 x ULN	4 2.9%	2 3%	0 0%	6 4.4%
Post-Baseline ALT or AST > 5 x ULN	0 0%	0 0%	0 0%	0 0%
Post-Baseline TBL > 1 x ULN	12 8.8%	3 4.5%	6 4.4%	21 15.3%
Post-Baseline TBL > 1.5 x ULN	0 0%	0 0%	0 0%	0 0%
Post-Baseline TBL > 2 x ULN	0 0%	0 0%	0 0%	0 0%
Post-Baseline ALP > 1.5 x ULN	0 0%	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP
Description	Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 24 (Wk24) are presented.
Time Frame	Baseline (last assessment prior to first dose of IP), week 24

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least one dose of IP. Participants with an assessment at week 24.

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.
Measure Participants	135	65	130	134
↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk24	3 2.2%	2 3%	1 0.7%	3 2.2%
↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk24	14 10.3%	6 9%	14 10.4%	8 5.8%
↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk24	1 0.7%	1 1.5%	0 0%	2 1.5%
↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk24	0 0%	2 3%	0 0%	3 2.2%

11. Secondary Outcome

Title	Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP
Description	Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 100 (Wk100) are presented.
Time Frame	Pre-OLTP Baseline (last assessment prior to first dose of IP in OLTP), week 100

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least one dose of IP in the OLTP. Participants with an assessment at week 100.

Arm/Group Title	OLTP: 70 mg SC QM (Only)	OLTP: 140 mg SC QM (Only)	OLTP: 70/140 mg SC QM (Both)	OLTP: Total
Arm/Group Description	Participants who received only erenumab 70 mg SC QM in the OLTP	Participants who received only erenumab 140 mg SC QM in the OLTP	Participants who received both erenumab 70 mg and 140 mg SC QM in the OLTP	Participants who received erenumab 70 mg and/or 140 mg SC QM in the OLTP
Measure Participants	245	68	112	425
↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk100	8 5.9%	0 0%	2 1.5%	10 7.3%
↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk100	25 18.4%	10 14.9%	10 7.4%	45 32.8%
↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk100	4 2.9%	0 0%	1 0.7%	5 3.6%
↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk100	7 5.1%	2 3%	0 0%	9 6.6%

12. Secondary Outcome

Title	Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab
Description	Data are summarized by the treatment participants received during the double-blind treatment phase. Placebo participants may have received erenumab 70 mg or 140 mg during the OLTP. Baseline is defined as the last antibody assessment on or prior to the first dose of erenumab. Transient binding/neutralizing antibody responses are defined as a negative (neg) result at the participant's last timepoint tested among participants who developed binding/neutralizing antibodies post-baseline.
Time Frame	Baseline (first dose of erenumab) up to end of study (week 100) plus 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least one dose of IP. Participants who received at least one dose of erenumab (during the DBTP and/or OLTP).

Arm/Group Title	DBTP: Placebo	DBTP: Erenumab 28 mg QM	DPTP: Erenumab 70 mg QM	DBTP: Erenumab 140 mg QM
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.	Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.
Measure Participants	133	66	135	137
Binding Antibody Positive (BAb+) at Baseline (BL)	0 0%	0 0%	0 0%	0 0%
Neutralizing Antibody Positive (NAb+) at BL	0 0%	0 0%	0 0%	0 0%
BAb+ Post-BL With a Neg/No Result at BL	4 2.9%	5 7.5%	6 4.4%	0 0%
Transient BAb+ Post-BL With a Neg/No Result at BL	2 1.5%	4 6%	5 3.7%	0 0%
NAb+ Post-BL With a Neg/No Result at BL	0 0%	0 0%	0 0%	0 0%
Transient NAb+ Post-BL With a Neg/No Result at BL	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	All-cause mortality: from randomization through the end of study (up to 116 weeks). Treatment-emergent serious and non-serious events: - DBTP: from first dose of IP up to week 24 (end of DBTP) - OLTP: from first dose of OL IP (week 24) up to week 100 (end of OLTP) plus 12 weeks - CHU sub-study: from first dose of sub-study IP up to day 85 (end of sub-study)
Adverse Event Reporting Description	All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Arm/Group Title	DBTP: Placebo		DBTP: Erenumab 28 mg QM		DPTP: Erenumab 70 mg QM		DBTP: Erenumab 140 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP Total: Erenumab 70/140 mg QM		CHU Sub-Study: Two Erenumab 70 mg/mL AI/Pens		CHU Sub-Study: One Erenumab 140 mg/mL AI/Pen		CHU Sub-Study Total
Arm/Group Description	Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.		Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.		Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.		Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP.		Erenumab 70 mg SC QM in the OLTP (at the time of the event).		Erenumab 140 mg SC QM in the OLTP (at the time of the event).		Erenumab 70 mg and/or 140 mg SC QM in the OLTP.		Self-administered erenumab via two 70 mg/mL AI/pens on day 1, day 29 and day 57 of the CHU sub-study.		Self-administered erenumab via one 140 mg/mL AI/pen on day 1, day 29 and day 57 of the CHU sub-study.		Self-administered erenumab via two 70 mg/mL AI/pens or one 140 mg/mL AI/pen on day 1, day 29 and day 57 of the CHU sub-study.
All Cause Mortality
	DBTP: Placebo		DBTP: Erenumab 28 mg QM		DPTP: Erenumab 70 mg QM		DBTP: Erenumab 140 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP Total: Erenumab 70/140 mg QM		CHU Sub-Study: Two Erenumab 70 mg/mL AI/Pens		CHU Sub-Study: One Erenumab 140 mg/mL AI/Pen		CHU Sub-Study Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/136 (0%)		0/67 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		0/189 (0%)		0/459 (0%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Serious Adverse Events
	DBTP: Placebo		DBTP: Erenumab 28 mg QM		DPTP: Erenumab 70 mg QM		DBTP: Erenumab 140 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP Total: Erenumab 70/140 mg QM		CHU Sub-Study: Two Erenumab 70 mg/mL AI/Pens		CHU Sub-Study: One Erenumab 140 mg/mL AI/Pen		CHU Sub-Study Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/136 (2.9%)		1/66 (1.5%)		1/135 (0.7%)		1/137 (0.7%)		18/386 (4.7%)		9/189 (4.8%)		27/459 (5.9%)		1/24 (4.2%)		0/25 (0%)		1/49 (2%)
Cardiac disorders
Prinzmetal angina	1/136 (0.7%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		0/189 (0%)		0/459 (0%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Ear and labyrinth disorders
Vertigo positional	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Eye disorders
Eyelid ptosis	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Gastrointestinal disorders
Haemorrhoids	1/136 (0.7%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Diverticulum intestinal haemorrhagic	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Enterocolitis	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Large intestine polyp	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Infections and infestations
Gastroenteritis	0/136 (0%)		0/66 (0%)		0/135 (0%)		1/137 (0.7%)		0/386 (0%)		0/189 (0%)		0/459 (0%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Intestinal tuberculosis	0/136 (0%)		0/66 (0%)		0/135 (0%)		1/137 (0.7%)		0/386 (0%)		0/189 (0%)		0/459 (0%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Diverticulitis	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Meningitis viral	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Mycobacterial infection	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		1/24 (4.2%)		0/25 (0%)		1/49 (2%)
Pharyngitis	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Tonsillitis	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Injury, poisoning and procedural complications
Hand fracture	0/136 (0%)		1/66 (1.5%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Cartilage injury	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Clavicle fracture	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Meniscus injury	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Muscle rupture	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Postoperative ileus	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Tendon rupture	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Tooth fracture	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Metabolism and nutrition disorders
Dehydration	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	0/136 (0%)		0/66 (0%)		1/135 (0.7%)		0/137 (0%)		0/386 (0%)		0/189 (0%)		0/459 (0%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Chondropathy	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Extremity contracture	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Osteonecrosis	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	1/136 (0.7%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		0/189 (0%)		0/459 (0%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Breast cancer	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Colon adenoma	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Intraductal proliferative breast lesion	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Uterine leiomyoma	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Nervous system disorders
Migraine	1/136 (0.7%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		0/189 (0%)		0/459 (0%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Headache	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Intracranial aneurysm	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Myelopathy	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Psychiatric disorders
Depression	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		0/386 (0%)		1/189 (0.5%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Reproductive system and breast disorders
Cervical dysplasia	0/136 (0%)		0/66 (0%)		0/135 (0%)		0/137 (0%)		1/386 (0.3%)		0/189 (0%)		1/459 (0.2%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	DBTP: Placebo		DBTP: Erenumab 28 mg QM		DPTP: Erenumab 70 mg QM		DBTP: Erenumab 140 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP Total: Erenumab 70/140 mg QM		CHU Sub-Study: Two Erenumab 70 mg/mL AI/Pens		CHU Sub-Study: One Erenumab 140 mg/mL AI/Pen		CHU Sub-Study Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/136 (40.4%)		28/66 (42.4%)		67/135 (49.6%)		58/137 (42.3%)		231/386 (59.8%)		133/189 (70.4%)		343/459 (74.7%)		7/24 (29.2%)		7/25 (28%)		14/49 (28.6%)
Gastrointestinal disorders
Abdominal pain upper	1/136 (0.7%)		1/66 (1.5%)		5/135 (3.7%)		2/137 (1.5%)		22/386 (5.7%)		4/189 (2.1%)		26/459 (5.7%)		0/24 (0%)		1/25 (4%)		1/49 (2%)
Constipation	2/136 (1.5%)		0/66 (0%)		7/135 (5.2%)		7/137 (5.1%)		14/386 (3.6%)		5/189 (2.6%)		19/459 (4.1%)		0/24 (0%)		1/25 (4%)		1/49 (2%)
Dental caries	3/136 (2.2%)		2/66 (3%)		7/135 (5.2%)		2/137 (1.5%)		17/386 (4.4%)		9/189 (4.8%)		26/459 (5.7%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Infections and infestations
Gastroenteritis	4/136 (2.9%)		2/66 (3%)		2/135 (1.5%)		4/137 (2.9%)		27/386 (7%)		15/189 (7.9%)		41/459 (8.9%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Nasopharyngitis	41/136 (30.1%)		22/66 (33.3%)		39/135 (28.9%)		45/137 (32.8%)		174/386 (45.1%)		109/189 (57.7%)		274/459 (59.7%)		5/24 (20.8%)		6/25 (24%)		11/49 (22.4%)
Pharyngitis	3/136 (2.2%)		3/66 (4.5%)		5/135 (3.7%)		3/137 (2.2%)		22/386 (5.7%)		7/189 (3.7%)		28/459 (6.1%)		1/24 (4.2%)		0/25 (0%)		1/49 (2%)
Cystitis	3/136 (2.2%)		1/66 (1.5%)		1/135 (0.7%)		2/137 (1.5%)		18/386 (4.7%)		8/189 (4.2%)		26/459 (5.7%)		0/24 (0%)		0/25 (0%)		0/49 (0%)
Influenza	4/136 (2.9%)		1/66 (1.5%)		3/135 (2.2%)		1/137 (0.7%)		46/386 (11.9%)		29/189 (15.3%)		75/459 (16.3%)		1/24 (4.2%)		0/25 (0%)		1/49 (2%)
Musculoskeletal and connective tissue disorders
Back pain	2/136 (1.5%)		3/66 (4.5%)		7/135 (5.2%)		1/137 (0.7%)		28/386 (7.3%)		7/189 (3.7%)		34/459 (7.4%)		1/24 (4.2%)		0/25 (0%)		1/49 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.