Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01952574
• Collaborator: (none)
• Enrollment: 483
• Locations: 66
• Arms: 6
• Actual Duration (Months): 75.2
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A study to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days in participants with episodic migraine.

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

Detailed Description

The study is composed of an initial screening phase (up to 3 weeks), a 4-week baseline phase, a 12-week double-blind treatment phase (DBTP), an open-label treatment phase (OLTP) for up to 256 weeks, and an 8-week safety follow-up (12 weeks after the last dose of investigational product [IP]).

In the DBTP participants were to be randomized in a 3:2:2:2 ratio to placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg.

During the open-label treatment phase, participants were to receive erenumab 70 mg QM from week 12 to week 264. After implementation of Protocol Amendment 3 (07 April 2016), participants remaining in the OLTP increased their dose to erenumab 140 mg QM up to week 264. The safety follow-up increased from an 8-week safety follow-up to a 12-week safety follow-up (16 weeks after the last dose of investigational product).

During the OLTP participants enrolled at sites in the United States could enroll in an optional clinical home use (CHU) substudy, per a country-specific protocol amendment dated 20 June 2016. Participants in the CHU substudy were to be randomized 1:1 into 1 of 2 treatment groups: erenumab 140 mg using a prefilled syringe or erenumab 140 mg using an autoinjector/pen. Day 1 of the CHU substudy corresponded with any OLTP study visit up through Week 256, as long as the participant had received at least 2 doses of erenumab 140 mg. During the CHU substudy, participants initially self-administered IP under site supervision on substudy day 1, and then self-administered IP at home on substudy days 29 and 57.

Study Design

• Study Type: Interventional
• Actual Enrollment: 483 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: In the DBTP participants were randomized to one of four arms. In the optional CHU substudy participants were randomized into one of two treatment groups.In the DBTP participants were randomized to one of four arms. In the optional CHU substudy participants were randomized into one of two treatment groups.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• 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: Aug 6, 2013
• Actual Primary Completion Date: Sep 25, 2014
• Actual Study Completion Date: Nov 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Drug: Erenumab; Administered by study site staff once a month (QM) as a subcutaneous injection; Other Names: AMG 334 Aimovig™ ; Drug: Placebo; Administered by study site staff once a month (QM) as a subcutaneous injection
Experimental: Erenumab 7 mg QM Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Drug: Erenumab; Administered by study site staff once a month (QM) as a subcutaneous injection; Other Names: AMG 334 Aimovig™
Experimental: Erenumab 21 mg QM Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Drug: Erenumab; Administered by study site staff once a month (QM) as a subcutaneous injection; Other Names: AMG 334 Aimovig™
Experimental: Erenumab 70 mg QM Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Drug: Erenumab; Administered by study site staff once a month (QM) as a subcutaneous injection; Other Names: AMG 334 Aimovig™
Experimental: CHU Substudy: Erenumab 140 mg PFS Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).	Drug: Erenumab PFS; Erenumab supplied in a single-use prefilled syringe for self-administration in the CHU substudy
Experimental: CHU Substudy: Erenumab 140 mg AI/Pen Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).	Drug: Erenumab AI/Pen; Erenumab supplied in a single-use autoinjector/pen for self-administration in the CHU substudy

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Monthly Migraine Days at Week 12 [4-week baseline phase and the last 4 weeks of the 12-week 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 as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the number of migraine days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.

2. CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab [CHU substudy day 29 (week 4) and day 57 (week 8)]

   To assess participants ability to administer a full dose of erenumab in home-use at day 29 (week 4) and day 57 (week 8), site staff called participants and asked whether the participant administered a full, partial, or no dose of erenumab. A full dose means that the entire volume of both prefilled syringes or autoinjector/pens were injected. Discontinued prior to dosing day indicates participants who had discontinued the investigational product and did not attempt to self-administer on day 29 or 57.

Secondary Outcome Measures

1. Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12 [4-week baseline phase and the last 4 weeks of the 12-week 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. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the last 4 weeks of double-blind treatment. 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 4 weeks of the 12-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.

2. Change From Baseline in Monthly Migraine Attacks at Week 12 [4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase]

   A migraine attack is an episode of any qualified migraine headache or migraine specific medication intakes for aura only. A migraine attack that was interrupted by sleep or that temporarily remits and then recurs within 48 hours or an attack treated successfully with medication but that relapses within 48 hours was considered to be one attack. The change from baseline in monthly migraine attacks was calculated as the number of migraine attacks during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine attacks during the 4-week baseline phase.

3. Number of Participants With Treatment-emergent Adverse Events in the Double-blind Treatment Phase [From first dose of study drug in the double-blind treatment phase until the first dose of study drug in the open-label treatment phase (12 weeks) or up to 12 weeks after last dose for participants who did not enter the open-label treatment phase.]

   An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Mild; asymptomatic or mild symptoms Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care Life-threatening consequences; urgent intervention indicated Death related to AE A serious adverse event is an AE that meets at least 1 of the following 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

4. Number of Participants With Treatment-emergent Adverse Events in the Open-label Treatment Phase [From first dose in the open-label treatment phase up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; a maximum of 268 weeks.]

   An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Mild; asymptomatic or mild symptoms Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care Life-threatening consequences; urgent intervention indicated Death related to AE A serious adverse event is an AE that meets at least 1 of the following 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

5. CHU Substudy: Number of Participants With Treatment-emergent Adverse Events During the CHU Substudy [From first dose in the CHU substudy to end of substudy (up to 12 weeks)]

   AEs were graded using the CTCAE version 4.03: Mild; asymptomatic or mild symptoms Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care Life-threatening consequences; urgent intervention indicated Death related to AE A serious adverse event is an AE that meets at least 1 of the following 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 An adverse device effect is any AE related to the use of a medical device, including AEs resulting from insufficient or inadequate instructions for use, any malfunction of the device, or use error or from intentional misuse of the device.

6. Number of Participants Who Developed Anti-erenumab Antibodies During the Double-blind Treatment Phase [12 weeks]

   Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. Participants who developed anti-erenumab antibodies are participants who were negative or had no result at baseline but positive at any time postbaseline during the DBTP. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.

7. Number of Participants Who Developed Anti-erenumab Antibodies During the Open-label Treatment Phase [From week 12 up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks.]

   Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. Participants who developed anti-erenumab antibodies are participants who were negative prior to the first OLTP dose but positive at any time during the OLTP, or participants with no data prior to first dose in OLTP with any post-baseline positive results. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of migraine for more than12 months prior to screening

• Migraine frequency: ≥ 4 and ≤ 14 migraine days per month in each of the 3 months prior to screening and during baseline phase

• Headache frequency: < 15 headache days per month (with > 50% of the headache days being migraine days) in each of the 3 months prior to screening and during baseline phase

• Demonstrated at least 80% compliance with the eDiary during baseline phase

Exclusion Criteria:

• Older than 50 years of age at migraine onset

• History of cluster headache or basilar or hemiplegic migraine headache

• Unable to differentiate migraine from other headaches

• No therapeutic response with > 2 of the following eight medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. Medication categories are:

• 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: Venlafaxine, desvenlafaxine, duloxetine, milnacipran

• Category 6: Flunarizine, verapamil

• Category 7: Lisinopril, candesartan

• Category 8: Butterbur, feverfew, magnesium (≥ 600 mg/day), riboflavin (≥ 100 mg/day)

• Overuse of acute migraine medications in any month during the 3 months prior to screening or during screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85032
2	Research Site	Long Beach	California	United States	90806
3	Research Site	National City	California	United States	91950
4	Research Site	Newport Beach	California	United States	92663
5	Research Site	San Francisco	California	United States	94109
6	Research Site	Santa Monica	California	United States	90404
7	Research Site	Sherman Oaks	California	United States	91403
8	Research Site	Spring Valley	California	United States	91978
9	Research Site	Danbury	Connecticut	United States	06810
10	Research Site	Fairfield	Connecticut	United States	06824
11	Research Site	Stamford	Connecticut	United States	06905
12	Research Site	Bradenton	Florida	United States	34205
13	Research Site	Melbourne	Florida	United States	32935
14	Research Site	Palm Beach Gardens	Florida	United States	33410
15	Research Site	West Palm Beach	Florida	United States	33407
16	Research Site	Decatur	Georgia	United States	30033
17	Research Site	Wichita	Kansas	United States	67207
18	Research Site	Lexington	Kentucky	United States	40513
19	Research Site	Louisville	Kentucky	United States	40213
20	Research Site	Watertown	Massachusetts	United States	02472
21	Research Site	Worcester	Massachusetts	United States	01605
22	Research Site	Ann Arbor	Michigan	United States	48104
23	Research Site	Kalamazoo	Michigan	United States	49009
24	Research Site	Southfield	Michigan	United States	48034
25	Research Site	Plymouth	Minnesota	United States	55441
26	Research Site	Saint Louis	Missouri	United States	63141
27	Research Site	Springfield	Missouri	United States	65807
28	Research Site	Rochester	New York	United States	14609
29	Research Site	Greensboro	North Carolina	United States	27405
30	Research Site	Raleigh	North Carolina	United States	27612
31	Research Site	Philadelphia	Pennsylvania	United States	19107
32	Research Site	Nashville	Tennessee	United States	37203
33	Research Site	Arlington	Texas	United States	76017
34	Research Site	Austin	Texas	United States	78731
35	Research Site	Dallas	Texas	United States	75214
36	Research Site	Dallas	Texas	United States	75231
37	Research Site	Houston	Texas	United States	77074
38	Research Site	Salt Lake City	Utah	United States	84106
39	Research Site	Salt Lake City	Utah	United States	84124
40	Research Site	Falls Church	Virginia	United States	22042
41	Research Site	Virginia Beach	Virginia	United States	23454
42	Research Site	Toronto	Ontario	Canada	M4S 1Y2
43	Research Site	Montreal	Quebec	Canada	H2L 4M1
44	Research Site	Aarhus C		Denmark	8000
45	Research Site	Glostrup		Denmark	2600
46	Research Site	Helsinki		Finland	00100
47	Research Site	Mikkeli		Finland	50100
48	Research Site	Oulu		Finland	90220
49	Research Site	Tampere		Finland	33100
50	Research Site	Turku		Finland	20100
51	Research Site	Berlin		Germany	10117
52	Research Site	Berlin		Germany	10409
53	Research Site	Berlin		Germany	10435
54	Research Site	Bochum		Germany	44789
55	Research Site	Essen		Germany	45133
56	Research Site	Hamburg		Germany	20246
57	Research Site	Leipzig		Germany	04107
58	Research Site	Hamar		Norway	2317
59	Research Site	Sandvika		Norway	1337
60	Research Site	Stavanger		Norway	4005
61	Research Site	Ålesund		Norway	6003
62	Research Site	Falköping		Sweden	521 37
63	Research Site	Lund		Sweden	222 22
64	Research Site	Stockholm		Sweden	112 45
65	Research Site	Stockholm		Sweden	114 33
66	Research Site	Vällingby		Sweden	162 68

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Ashina M, Dodick D, Goadsby PJ, Reuter U, Silberstein S, Zhang F, Gage JR, Cheng S, Mikol DD, Lenz RA. Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study. Neurology. 2017 Sep 19;89(12):1237-1243. doi: 10.1212/WNL.0000000000004391. Epub 2017 Aug 23.
• Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick D, Rippon GA, Klatt J, Xue F, Chia V, Zhang F, Cheng S, Mikol DD. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia. 2019 Oct;39(11):1455-1464. doi: 10.1177/0333102419854082. Epub 2019 May 30.
• Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick DW, Xue F, Zhang F, Paiva da Silva Lima G, Cheng S, Mikol DD. Long-term efficacy and safety of erenumab in migraine prevention: Results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol. 2021 May;28(5):1716-1725. doi: 10.1111/ene.14715. Epub 2021 Jan 20.
• 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.
• Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, Saper J, Cady R, Chon Y, Dietrich J, Lenz R. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Apr;15(4):382-90. doi: 10.1016/S1474-4422(16)00019-3. Epub 2016 Feb 12.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01952574
• Other Study ID Numbers: 20120178; 2012-005331-90
• First Posted: Sep 30, 2013
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Amgen: migraine, headache, prevention, prophylaxis
• Additional relevant MeSH terms: Migraine Disorders; Erenumab; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	This study was conducted at 59 centers in North America (Canada, USA) and Europe (Denmark, Finland, Germany, Norway, Sweden, and Portugal). The study consisted of a 12-week double-blind treatment phase (DBTP) and a 256-week open-label treatment phase (OLTP) followed by a safety follow-up of 8 to 12 weeks (12 -16 weeks after last dose). The OLTP portion of the study was not conducted in Norway.
Pre-assignment Detail	Participants were randomized 3:2:2:2 to receive placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg once a month (QM) in the double-blind phase. Randomization was stratified by region (North America vs. Europe). During the open-label treatment phase, participants in the United States (US) could participate in an optional Clinical Home Use (CHU) substudy.

Arm/Group Title	DBTP: Placebo QM	DBTP: Erenumab 7 mg QM	DBTP: Erenumab 21 mg QM	DBTP: Erenumab 70 mg QM	OLTP: Erenumab 70/140 mg QM	CHU Substudy: Erenumab 140 mg by Prefilled Syringe	CHU Substudy: Erenumab 140 mg Autoinjector/Pen
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received 70 mg erenumab QM from the beginning of the OLTP (week 12). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).	Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using an autoinjector (AI)/pen on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).
Period Title: Double-blind Treatment Phase
STARTED	160	108	108	107	0	0	0
Received Study Drug	153	108	105	106	0	0	0
COMPLETED	143	105	99	101	0	0	0
NOT COMPLETED	17	3	9	6	0	0	0
Period Title: Double-blind Treatment Phase
STARTED	0	0	0	0	383	0	0
Received 70 mg Erenumab	0	0	0	0	383	0	0
Received 140 mg Erenumab	0	0	0	0	250	0	0
COMPLETED	0	0	0	0	221	0	0
NOT COMPLETED	0	0	0	0	162	0	0
Period Title: Double-blind Treatment Phase
STARTED	0	0	0	0	0	42	41
COMPLETED	0	0	0	0	0	39	40
NOT COMPLETED	0	0	0	0	0	3	1

Baseline Characteristics

Arm/Group Title	Placebo	Erenumab 7 mg QM	Erenumab 21 mg QM	Erenumab 70 mg QM	Total
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Total of all reporting groups
Overall Participants	160	108	108	107	483
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.4 (10.0)	40.3 (10.9)	39.9 (12.3)	42.6 (9.9)	41.1 (10.8)
Sex: Female, Male (Count of Participants)
Female	132 82.5%	88 81.5%	87 80.6%	82 76.6%	389 80.5%
Male	28 17.5%	20 18.5%	21 19.4%	25 23.4%	94 19.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 6.9%	9 8.3%	9 8.3%	1 0.9%	30 6.2%
Not Hispanic or Latino	149 93.1%	99 91.7%	99 91.7%	106 99.1%	453 93.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 1.3%	0 0%	1 0.9%	1 0.9%	4 0.8%
Black or African American	13 8.1%	10 9.3%	7 6.5%	2 1.9%	32 6.6%
Native Hawaiian or other Pacific Islander	1 0.6%	0 0%	0 0%	0 0%	1 0.2%
White	142 88.8%	97 89.8%	100 92.6%	103 96.3%	442 91.5%
Multiple	0 0%	0 0%	0 0%	1 0.9%	1 0.2%
Other	2 1.3%	1 0.9%	0 0%	0 0%	3 0.6%
Region (Count of Participants)
North America	85 53.1%	58 53.7%	58 53.7%	58 54.2%	259 53.6%
Europe	75 46.9%	50 46.3%	50 46.3%	49 45.8%	224 46.4%
Monthly Migraine Days (migraine days/month) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [migraine days/month]	8.77 (2.72)	8.62 (2.79)	8.93 (2.88)	8.58 (2.49)	8.73 (2.72)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Monthly Migraine Days at Week 12
Description	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 as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the number of migraine days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.
Time Frame	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of investigational product (IP) and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set), and with at least one change from baseline value in monthly migraine days.

Arm/Group Title	Placebo	Erenumab 7 mg QM	Erenumab 21 mg QM	Erenumab 70 mg QM
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Measure Participants	152	107	99	104
Least Squares Mean (Standard Error) [migraine days / month]	-2.28 (0.31)	-2.18 (0.36)	-2.39 (0.38)	-3.40 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 70 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
	Type of Statistical Test	Superiority
	Comments	To maintain the type I error at ≤ 0.05, the pairwise comparison was tested in a sequential testing procedure in the order of erenumab 70 mg vs placebo, 21 mg vs placebo, and 7 mg vs placebo. The lower dose group was only to be tested when the higher dose group was tested as significant.
Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.12
	Confidence Interval	(2-Sided) 95%; -2.06 to -0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 21 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
	Type of Statistical Test	Superiority
	Comments	To maintain the type I error at ≤ 0.05, the pairwise comparison was tested in a sequential testing procedure in the order of erenumab 70 mg vs placebo, 21 mg vs placebo, and 7 mg vs placebo. The lower dose group was only to be tested when the higher dose group was tested as significant.
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -1.07 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 7 mg QM
	Comments	The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
	Type of Statistical Test	Superiority
	Comments	To maintain the type I error at ≤ 0.05, the pairwise comparison was tested in a sequential testing procedure in the order of erenumab 70 mg vs placebo, 21 mg vs placebo, and 7 mg vs placebo. The lower dose group was only to be tested when the higher dose group was tested as significant.
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Generalized Linear Mixed Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 92%; -0.83 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12
Description	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 and during the last 4 weeks of double-blind treatment. 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 4 weeks of the 12-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.
Time Frame	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of investigational product and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set) with available data at week 12.

Arm/Group Title	Placebo	Erenumab 7 mg QM	Erenumab 21 mg QM	Erenumab 70 mg QM
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Measure Participants	144	104	93	99
Number [percentage of participants]	29.9 18.7%	28.8 26.7%	34.4 31.9%	46.5 43.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 70 mg QM
	Comments	The generalized linear mixed model includes data for all participants in the efficacy analysis set with at least one percent change from baseline value in monthly migraine days (152 participants in the placebo group and 104 in the erenumab 70 mg group)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Generalised Linear Mixed Model
	Comments	Generalized linear mixed model including treatment, visit, treatment by visit, stratification factor region, and baseline value as covariates.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 95%; 1.17 to 3.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 21 mg QM
	Comments	The generalized linear mixed model includes data for all participants in the efficacy analysis set with at least one change from baseline value in monthly migraine days (152 participants in the placebo group and 99 in the erenumab 21 mg group)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Generalized Linear Mixed Model
	Comments	Generalized linear mixed model including treatment, visit, treatment by visit, stratification factor region, and baseline value as covariates.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 0.71 to 2.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 7 mg QM
	Comments	The generalized linear mixed model includes data for all participants in the efficacy analysis set with at least one change from baseline value in monthly migraine days (152 participants in the placebo group and 107 in the erenumab 7 mg group)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Generalized Linear Mixed Model
	Comments	Generalized linear mixed model including treatment, visit, treatment by visit, stratification factor region, and baseline value as covariates.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Monthly Migraine Attacks at Week 12
Description	A migraine attack is an episode of any qualified migraine headache or migraine specific medication intakes for aura only. A migraine attack that was interrupted by sleep or that temporarily remits and then recurs within 48 hours or an attack treated successfully with medication but that relapses within 48 hours was considered to be one attack. The change from baseline in monthly migraine attacks was calculated as the number of migraine attacks during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine attacks during the 4-week baseline phase.
Time Frame	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of investigational product and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set), and with at least one change from baseline value in monthly migraine attacks.

Arm/Group Title	Placebo	Erenumab 7 mg QM	Erenumab 21 mg QM	Erenumab 70 mg QM
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Measure Participants	152	107	99	104
Least Squares Mean (Standard Error) [migraine attacks/month]	-1.44 (0.17)	-1.07 (0.20)	-1.42 (0.21)	-1.84 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 70 mg QM
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Generalized Linear Mixed Model
	Comments	Generalized linear mixed model including treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.92 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 21 mg QM
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Generalized Linear Mixed Model
	Comments	Generalized linear mixed model including treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.51 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erenumab 7 mg QM
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Generalized Linear Mixed Model
	Comments	Generalized linear mixed model including treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab
Description	To assess participants ability to administer a full dose of erenumab in home-use at day 29 (week 4) and day 57 (week 8), site staff called participants and asked whether the participant administered a full, partial, or no dose of erenumab. A full dose means that the entire volume of both prefilled syringes or autoinjector/pens were injected. Discontinued prior to dosing day indicates participants who had discontinued the investigational product and did not attempt to self-administer on day 29 or 57.
Time Frame	CHU substudy day 29 (week 4) and day 57 (week 8)

Outcome Measure Data

Analysis Population Description

Participants enrolled in the CHU substudy who received at least 1 dose of investigational product in the substudy.

Arm/Group Title	CHU Substudy: Erenumab 140 mg Prefilled Syringe	CHY SubStudy: Erenumab 140 mg Autoinjector/Pen
Arm/Group Description	Participants in the open-label treatment phase in the United States self-administered 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).	Participants in the open-label treatment phase in the United States self-administered 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).
Measure Participants	42	41
Full dose	39 24.4%	41 38%
Partial dose	1 0.6%	0 0%
Discontinued prior to dosing day	2 1.3%	0 0%
Full dose	39 24.4%	39 36.1%
Partial dose	0 0%	1 0.9%
Discontinued prior to dosing day	3 1.9%	1 0.9%

5. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events in the Double-blind Treatment Phase
Description	An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Mild; asymptomatic or mild symptoms Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care Life-threatening consequences; urgent intervention indicated Death related to AE A serious adverse event is an AE that meets at least 1 of the following 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
Time Frame	From first dose of study drug in the double-blind treatment phase until the first dose of study drug in the open-label treatment phase (12 weeks) or up to 12 weeks after last dose for participants who did not enter the open-label treatment phase.

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least one dose of investigational product (safety analysis set).

Arm/Group Title	Placebo	Erenumab 7 mg QM	Erenumab 21 mg QM	Erenumab 70 mg QM
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Measure Participants	153	108	105	106
Any adverse event (AE)	81 50.6%	57 52.8%	55 50.9%	57 53.3%
Serious adverse events (SAEs)	1 0.6%	1 0.9%	0 0%	1 0.9%
AE leading to discontinuation of IP	2 1.3%	2 1.9%	2 1.9%	3 2.8%
AE Grade ≥ 2	36 22.5%	31 28.7%	25 23.1%	23 21.5%
AE Grade ≥ 3	3 1.9%	3 2.8%	3 2.8%	3 2.8%
AE Grade ≥ 4	0 0%	0 0%	0 0%	0 0%
Fatal adverse events	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events in the Open-label Treatment Phase
Description	An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Mild; asymptomatic or mild symptoms Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care Life-threatening consequences; urgent intervention indicated Death related to AE A serious adverse event is an AE that meets at least 1 of the following 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
Time Frame	From first dose in the open-label treatment phase up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; a maximum of 268 weeks.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of investigational product in the open-label treatment phase (open-label treatment phase set).

Arm/Group Title	OLTP: Erenumab 70 mg QM	OLTP: Erenumab 140 mg QM	OLTP: Erenumab 70/140 mg QM
Arm/Group Description	Participants received 70 mg erenumab QM from week 12 until implementation of Protocol Amendment 3 (07 April 2016) in the open-label treatment phase; median duration of exposure was 104 weeks.	After implementation of Protocol Amendment 3 (07 April 2016), participants still on study received erenumab 140 mg QM up to week 264 in the open-label treatment phase; median duration of exposure was 141 weeks.	Participants received 70 mg erenumab QM from the beginning of the OLTP (week 12). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.
Measure Participants	383	250	383
Any adverse event (AE)	323 201.9%	216 200%	340 314.8%
Serious adverse events (SAEs)	30 18.8%	25 23.1%	49 45.4%
AE leading to discontinuation of IP	16 10%	2 1.9%	18 16.7%
AE Grade ≥ 2	249 155.6%	180 166.7%	286 264.8%
AE Grade ≥ 3	55 34.4%	40 37%	83 76.9%
AE Grade ≥ 4	1 0.6%	3 2.8%	4 3.7%
Fatal adverse events	1 0.6%	1 0.9%	2 1.9%

7. Secondary Outcome

Title	CHU Substudy: Number of Participants With Treatment-emergent Adverse Events During the CHU Substudy
Description	AEs were graded using the CTCAE version 4.03: Mild; asymptomatic or mild symptoms Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care Life-threatening consequences; urgent intervention indicated Death related to AE A serious adverse event is an AE that meets at least 1 of the following 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 An adverse device effect is any AE related to the use of a medical device, including AEs resulting from insufficient or inadequate instructions for use, any malfunction of the device, or use error or from intentional misuse of the device.
Time Frame	From first dose in the CHU substudy to end of substudy (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

Participants enrolled in the CHU substudy who received at least 1 dose of investigational product in the substudy.

Arm/Group Title	CHU Substudy: Erenumab 140 mg Prefilled Syringe	CHY SubStudy: Erenumab 140 mg Autoinjector/Pen
Arm/Group Description	Participants in the open-label treatment phase in the United States self-administered 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).	Participants in the open-label treatment phase in the United States self-administered 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).
Measure Participants	42	41
Any adverse event	13 8.1%	17 15.7%
AE Grade ≥ 2	7 4.4%	10 9.3%
AE Grade ≥ 3	1 0.6%	2 1.9%
AE Grade ≥ 4	0 0%	0 0%
Serious adverse events	0 0%	0 0%
Leading to discontinuation of IP	0 0%	0 0%
Fatal adverse events	0 0%	0 0%
Injection site reactions	4 2.5%	2 1.9%
Adverse device effects	2 1.3%	2 1.9%

8. Secondary Outcome

Title	Number of Participants Who Developed Anti-erenumab Antibodies During the Double-blind Treatment Phase
Description	Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. Participants who developed anti-erenumab antibodies are participants who were negative or had no result at baseline but positive at any time postbaseline during the DBTP. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of IP and with valid postbaseline antibody testing results.

Arm/Group Title	Placebo	Erenumab 7 mg QM	Erenumab 21 mg QM	Erenumab 70 mg QM
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.	Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Measure Participants	149	107	104	106
Developed binding antibodies	0 0%	13 12%	12 11.1%	8 7.5%
Developed neutralizing antibodies	0 0%	5 4.6%	3 2.8%	1 0.9%

9. Secondary Outcome

Title	Number of Participants Who Developed Anti-erenumab Antibodies During the Open-label Treatment Phase
Description	Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. Participants who developed anti-erenumab antibodies are participants who were negative prior to the first OLTP dose but positive at any time during the OLTP, or participants with no data prior to first dose in OLTP with any post-baseline positive results. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.
Time Frame	From week 12 up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of IP in the OLTP and with valid antibody testing results during the OLTP.

Arm/Group Title	Placebo / Erenumab 70/140 mg QM	Erenumab 7 mg QM / Erenumab 70/140 mg QM	Erenumab 21 mg QM / Erenumab 70/140 mg QM	Erenumab 70 mg QM / Erenumab 70/140 mg QM
Arm/Group Description	Participants randomized to placebo in the double-blind treatment phase received 70 mg erenumab QM from week 12 in the open-label treatment phase. After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Participants randomized to erenumab 7 mg in the double-blind treatment phase received 70 mg erenumab QM from week 12 in the open-label treatment phase. After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Participants randomized to erenumab 21 mg in the double-blind treatment phase received 70 mg erenumab QM from week 12 in the open-label treatment phase. After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.	Participants randomized to erenumab 70 mg in the double-blind treatment phase received 70 mg erenumab QM from week 12 in the open-label treatment phase. After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.
Measure Participants	119	88	87	86
Developed binding antibodies	12 7.5%	8 7.4%	6 5.6%	5 4.7%
Developed neutralizing antibodies	1 0.6%	0 0%	1 0.9%	0 0%

Adverse Events

Time Frame	Double-blind Treatment Phase: From first dose of study drug in the DBTP until the first dose of study drug in the open-label treatment phase (12 weeks) or up to 12 weeks after last dose for participants who did not enter the open-label treatment phase. Open-label Treatment Phase: From first dose in the OLTP up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks. CHU substudy: 12 weeks
Arm/Group Title	DBTP: Placebo QM		DBTP: Erenumab 7 mg QM		DBTP: Erenumab 21 mg QM		DBTP: Erenumab 70 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP: Erenumab 70/140 mg QM		CHU Substudy: Erenumab 140 mg PFS		CHU Substudy: Erenumab 140 mg AI/Pen		CHU Substudy: Total
Arm/Group Description	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.		Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.		Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.		Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.		Participants received 70 mg erenumab QM from week 12 until implementation of Protocol Amendment 3 (07 April 2016) in the open-label treatment phase; median duration of exposure was 104 weeks.		After implementation of Protocol Amendment 3 (07 April 2016), participants still on study received erenumab 140 mg QM up to week 264 in the open-label treatment phase; median duration of exposure was 141 weeks.		Participants received 70 mg erenumab QM from the beginning of the OLTP (week 12). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.		Participants in the open-label treatment phase in the United States self-administered 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).		Participants in the open-label treatment phase in the United States self-administered 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).		Participants in the open-label treatment phase in the United States self-administered 140 mg erenumab via two 70 mg injections using a prefilled syringe or autoinjector/pen on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).
All Cause Mortality
	DBTP: Placebo QM		DBTP: Erenumab 7 mg QM		DBTP: Erenumab 21 mg QM		DBTP: Erenumab 70 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP: Erenumab 70/140 mg QM		CHU Substudy: Erenumab 140 mg PFS		CHU Substudy: Erenumab 140 mg AI/Pen		CHU Substudy: 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	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	DBTP: Placebo QM		DBTP: Erenumab 7 mg QM		DBTP: Erenumab 21 mg QM		DBTP: Erenumab 70 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP: Erenumab 70/140 mg QM		CHU Substudy: Erenumab 140 mg PFS		CHU Substudy: Erenumab 140 mg AI/Pen		CHU Substudy: 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	1/153 (0.7%)		1/108 (0.9%)		0/105 (0%)		1/106 (0.9%)		30/383 (7.8%)		25/250 (10%)		49/383 (12.8%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Blood and lymphatic system disorders
Anaemia	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Cardiac disorders
Coronary artery stenosis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Hypertensive heart disease	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Myocardial ischaemia	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Congenital, familial and genetic disorders
Developmental hip dysplasia	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Ear and labyrinth disorders
Vertigo	0/153 (0%)		0/108 (0%)		0/105 (0%)		1/106 (0.9%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Endocrine disorders
Primary hyperaldosteronism	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Eye disorders
Visual impairment	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Gastrointestinal disorders
Abdominal adhesions	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Abdominal hernia	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Appendicitis noninfective	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Colitis ischaemic	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Crohn's disease	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Diverticulum	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Faecaloma	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Gastrointestinal haemorrhage	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Intra-abdominal haematoma	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Pancreatic cyst	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Peritoneal haemorrhage	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Rectal prolapse	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
General disorders
Death	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Non-cardiac chest pain	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Hepatobiliary disorders
Cholecystitis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Hepatic cyst	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Infections and infestations
Abdominal abscess	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Appendicitis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		2/250 (0.8%)		2/383 (0.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Cellulitis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Diverticulitis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Gastroenteritis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Pneumonia klebsiella	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Tubo-ovarian abscess	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Urinary tract infection	1/153 (0.7%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		0/250 (0%)		0/383 (0%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Injury, poisoning and procedural complications
Ligament rupture	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		2/250 (0.8%)		3/383 (0.8%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Spinal compression fracture	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Investigations
Aspartate aminotransferase increased	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Lumbar spinal stenosis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Metatarsalgia	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Musculoskeletal chest pain	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Osteoarthritis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		1/250 (0.4%)		2/383 (0.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the cervix	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Breast cancer	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		2/383 (0.5%)		0/250 (0%)		2/383 (0.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Invasive lobular breast carcinoma	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Lipoma	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Lung adenocarcinoma stage III	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Prostate cancer	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Uterine leiomyoma	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		1/250 (0.4%)		2/383 (0.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Nervous system disorders
Migraine	0/153 (0%)		0/108 (0%)		0/105 (0%)		1/106 (0.9%)		0/383 (0%)		0/250 (0%)		0/383 (0%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Cauda equina syndrome	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Cervicobrachial syndrome	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Headache	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Lumbar radiculopathy	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Optic neuritis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Syncope	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		2/383 (0.5%)		0/250 (0%)		2/383 (0.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Psychiatric disorders
Adjustment disorder	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		1/250 (0.4%)		2/383 (0.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Suicide attempt	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Renal and urinary disorders
Bladder prolapse	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Pelvi-ureteric obstruction	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Reproductive system and breast disorders
Ovarian cyst ruptured	0/153 (0%)		1/108 (0.9%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		0/250 (0%)		0/383 (0%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Adnexa uteri cyst	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Menorrhagia	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Ovarian cyst	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		0/383 (0%)		1/250 (0.4%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Pulmonary embolism	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Vascular disorders
Arteriosclerosis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Deep vein thrombosis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		1/250 (0.4%)		2/383 (0.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Thrombosis	0/153 (0%)		0/108 (0%)		0/105 (0%)		0/106 (0%)		1/383 (0.3%)		0/250 (0%)		1/383 (0.3%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Other (Not Including Serious) Adverse Events
	DBTP: Placebo QM		DBTP: Erenumab 7 mg QM		DBTP: Erenumab 21 mg QM		DBTP: Erenumab 70 mg QM		OLTP: Erenumab 70 mg QM		OLTP: Erenumab 140 mg QM		OLTP: Erenumab 70/140 mg QM		CHU Substudy: Erenumab 140 mg PFS		CHU Substudy: Erenumab 140 mg AI/Pen		CHU Substudy: 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	45/153 (29.4%)		27/108 (25%)		24/105 (22.9%)		31/106 (29.2%)		220/383 (57.4%)		172/250 (68.8%)		264/383 (68.9%)		7/42 (16.7%)		9/41 (22%)		16/83 (19.3%)
Gastrointestinal disorders
Constipation	1/153 (0.7%)		0/108 (0%)		1/105 (1%)		3/106 (2.8%)		9/383 (2.3%)		15/250 (6%)		24/383 (6.3%)		1/42 (2.4%)		0/41 (0%)		1/83 (1.2%)
Nausea	2/153 (1.3%)		3/108 (2.8%)		1/105 (1%)		3/106 (2.8%)		13/383 (3.4%)		18/250 (7.2%)		29/383 (7.6%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
General disorders
Fatigue	3/153 (2%)		5/108 (4.6%)		2/105 (1.9%)		4/106 (3.8%)		19/383 (5%)		11/250 (4.4%)		29/383 (7.6%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Infections and infestations
Nasopharyngitis	12/153 (7.8%)		10/108 (9.3%)		6/105 (5.7%)		6/106 (5.7%)		82/383 (21.4%)		59/250 (23.6%)		111/383 (29%)		0/42 (0%)		2/41 (4.9%)		2/83 (2.4%)
Bronchitis	1/153 (0.7%)		0/108 (0%)		0/105 (0%)		1/106 (0.9%)		17/383 (4.4%)		14/250 (5.6%)		31/383 (8.1%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Influenza	5/153 (3.3%)		1/108 (0.9%)		4/105 (3.8%)		1/106 (0.9%)		36/383 (9.4%)		31/250 (12.4%)		56/383 (14.6%)		0/42 (0%)		1/41 (2.4%)		1/83 (1.2%)
Pneumonia	1/153 (0.7%)		0/108 (0%)		0/105 (0%)		1/106 (0.9%)		11/383 (2.9%)		11/250 (4.4%)		22/383 (5.7%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Sinusitis	2/153 (1.3%)		2/108 (1.9%)		1/105 (1%)		2/106 (1.9%)		30/383 (7.8%)		26/250 (10.4%)		53/383 (13.8%)		1/42 (2.4%)		1/41 (2.4%)		2/83 (2.4%)
Upper respiratory tract infection	3/153 (2%)		1/108 (0.9%)		2/105 (1.9%)		2/106 (1.9%)		52/383 (13.6%)		53/250 (21.2%)		78/383 (20.4%)		3/42 (7.1%)		2/41 (4.9%)		5/83 (6%)
Urinary tract infection	1/153 (0.7%)		0/108 (0%)		1/105 (1%)		1/106 (0.9%)		23/383 (6%)		23/250 (9.2%)		41/383 (10.7%)		0/42 (0%)		1/41 (2.4%)		1/83 (1.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/153 (3.3%)		1/108 (0.9%)		0/105 (0%)		1/106 (0.9%)		26/383 (6.8%)		13/250 (5.2%)		37/383 (9.7%)		0/42 (0%)		1/41 (2.4%)		1/83 (1.2%)
Back pain	4/153 (2.6%)		2/108 (1.9%)		4/105 (3.8%)		2/106 (1.9%)		30/383 (7.8%)		21/250 (8.4%)		48/383 (12.5%)		0/42 (0%)		1/41 (2.4%)		1/83 (1.2%)
Pain in extremity	1/153 (0.7%)		1/108 (0.9%)		2/105 (1.9%)		2/106 (1.9%)		16/383 (4.2%)		11/250 (4.4%)		25/383 (6.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Nervous system disorders
Headache	1/153 (0.7%)		4/108 (3.7%)		1/105 (1%)		3/106 (2.8%)		10/383 (2.6%)		11/250 (4.4%)		21/383 (5.5%)		1/42 (2.4%)		0/41 (0%)		1/83 (1.2%)
Respiratory, thoracic and mediastinal disorders
Cough	3/153 (2%)		2/108 (1.9%)		1/105 (1%)		0/106 (0%)		15/383 (3.9%)		14/250 (5.6%)		27/383 (7%)		0/42 (0%)		0/41 (0%)		0/83 (0%)
Oropharyngeal pain	1/153 (0.7%)		1/108 (0.9%)		2/105 (1.9%)		2/106 (1.9%)		15/383 (3.9%)		7/250 (2.8%)		20/383 (5.2%)		1/42 (2.4%)		0/41 (0%)		1/83 (1.2%)
Vascular disorders
Hypertension	2/153 (1.3%)		1/108 (0.9%)		0/105 (0%)		2/106 (1.9%)		14/383 (3.7%)		11/250 (4.4%)		25/383 (6.5%)		0/42 (0%)		0/41 (0%)		0/83 (0%)

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.