Ascending Multiple-Doses of Erenumab (AMG 334) in Healthy Adults and in Migraine Patients

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01723514
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 2
• Actual Duration (Months): 19.8
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine whether erenumab is safe and well tolerated in healthy adults and migraine patients. As part of the secondary objectives, this study will be conducted to characterize the pharmacokinetic (PK) profile of erenumab after multiple subcutaneous (SC) doses in healthy adults and migraine patients, as well as to characterize the effect of erenumab on the capsaicin induced increase in dermal blood flow after multiple SC doses in healthy adults and migraine patients.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Erenumab; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 334 in Healthy Subjects and in Migraine Patients
• Actual Study Start Date: Nov 14, 2012
• Actual Primary Completion Date: Jul 10, 2014
• Actual Study Completion Date: Jul 10, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erenumab Healthy participants and participants with migraine received subcutaneous doses of erenumab on days 1, 29 and 57.	Drug: Erenumab; Administered by subcutaneous injection once a month; Other Names: AMG-334 Aimovig™
Placebo Comparator: Placebo Healthy participants and participants with migraine received subcutaneous doses of placebo on days 1, 29 and 57.	Drug: Placebo; Administered by subcutaneous injection once a month

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [From first dose of study drug until a maximum of 168 days after last dose (225 days)]

   An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. The definition of adverse events includes worsening of a pre-existing medical condition. Laboratory value changes that require treatment or adjustment in current therapy are considered adverse events. Teatment-related adverse events (TRAEs) are those assessed by the investigator as being possibly related to study drug. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal life-threatening (places the subject at immediate risk of death) 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.

2. Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) [From first dose of study drug until a maximum of 168 days after last dose (225 days)]

   The C-SSRS is a measure of suicidal ideation and behavior. Ideation includes a wish to be dead or nonspecific thoughts about wanting to end life. Suicidal behavior includes actual attempts, interrupted or aborted attempts, and any preparatory acts.

3. Number of Participants Who Developed Anti-erenumab Antibodies [From first dose of study drug until a maximum of 168 days after last dose (225 days)]

   Participants who had a negative or no result at baseline and were antibody positive postbaseline. Blood samples were first tested for anti-erenumab binding antibodies, samples testing positive for binding antibodies were also tested for neutralizing antibodies.

Secondary Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) of Erenumab [Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)]

   Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

2. Time to Maximum Observed Concentration (Tmax) of Erenumab [Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)]

   Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

3. Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) [Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)]

   Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

4. Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) [Day 57 (assessed from predose to day 225))]

   Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

5. Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow [Baseline, Days 8, 57, 85, 113, 169 and 197]

   Inhibition of capsaicin-induced dermal blood flow (DBF) by erenumab was used to measure calcitonin gene-related peptide (CGRP) receptor antagonism. Capsaicin was applied at 2 sites on the volar surface of the participants' left or right forearms and a control mixture was applied to 1 site on the volar surface of either the participants' left or right forearm. Dermal blood flow was assessed by laser Doppler perfusion imaging and was done immediately before ('baseline') and 0.5 hours post-capsaicin on the surface of these 3 sites. Data reported are the least square geometric mean ratios for the post-capsaicin dermal blood flow to pre-capsaicin dermal blood flow. According to the protocol, not all cohorts had dermal blood flow measurements at all time points.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Healthy male and female subjects, as well as male or female subjects with migraines between 18 and 55 years of age, inclusive, with no history or evidence of clinically relevant medical disorders as determined by the investigator in consultation with the Amgen physician;

Exclusion Criteria:

• History or evidence of clinically significant disorder (including psychiatric), condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Leuven		Belgium	3000

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• de Hoon J, Van Hecken A, Vandermeulen C, Yan L, Smith B, Chen JS, Bautista E, Hamilton L, Waksman J, Vu T, Vargas G. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine. Clin Pharmacol Ther. 2018 May;103(5):815-825. doi: 10.1002/cpt.799. Epub 2017 Oct 24.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01723514
• Other Study ID Numbers: 20101268; 2012-003594-26
• First Posted: Nov 8, 2012
• Last Update Posted: Jan 18, 2019
• Last Verified: Aug 1, 2018

• Keywords provided by Amgen: Migraine
• Additional relevant MeSH terms: Migraine Disorders; Erenumab

Study Results

Participant Flow

Recruitment Details	This study enrolled healthy participants (Part A) and participants with onset of migraines before the age of 50 years, with or without aura for at least 6 months and 3 migraine attacks per month in the last 3 months (Part B). The study was conducted at a single center in Belgium.
Pre-assignment Detail	Healthy participants were randomized to 1 of 4 cohorts and migraine patients were randomized to 1 of 2 cohorts. Within each cohort participants were assigned to erenumab or placebo in a 3:1 ratio.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Period Title: Overall Study
STARTED	8	6	6	6	6	4	6	6
COMPLETED	8	6	6	6	6	4	6	6
NOT COMPLETED	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg	Total
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Total of all reporting groups
Overall Participants	8	6	6	6	6	4	6	6	48
Age (years) [Mean (Standard Deviation) ]
Healthy Participants	32.1 (13.0)	26.3 (5.7)	33.3 (14.1)	29.8 (8.6)	39.0 (13.8)	32.1 (11.6)
Migraine Participants	37.0 (11.9)	31.7 (11.0)	31.3 (12.6)	32.9 (11.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	1 16.7%	0 0%	2 33.3%	3 75%	4 66.7%	5 83.3%	15 31.3%
Male	8 100%	6 100%	5 83.3%	6 100%	4 66.7%	1 25%	2 33.3%	1 16.7%	33 68.8%
Race/Ethnicity, Customized (Count of Participants)
White	8 100%	6 100%	6 100%	6 100%	6 100%	4 100%	6 100%	6 100%	48 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. The definition of adverse events includes worsening of a pre-existing medical condition. Laboratory value changes that require treatment or adjustment in current therapy are considered adverse events. Teatment-related adverse events (TRAEs) are those assessed by the investigator as being possibly related to study drug. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal life-threatening (places the subject at immediate risk of death) 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 until a maximum of 168 days after last dose (225 days)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	8	6	6	6	6	4	6	6
Any adverse event	5 62.5%	6 100%	6 100%	6 100%	4 66.7%	4 100%	6 100%	6 100%
Serious adverse event	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	1 16.7%
AE leading to discontinuation of study drug	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%
AE leading to discontinuation from study	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Fatal adverse events	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Treatment-related adverse events	0 0%	0 0%	2 33.3%	3 50%	0 0%	1 25%	0 0%	1 16.7%
Treatment-related serious adverse events	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%
TRAE leading to discontinuation of study drug	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%
TRAE leading to discontinuation from study	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS is a measure of suicidal ideation and behavior. Ideation includes a wish to be dead or nonspecific thoughts about wanting to end life. Suicidal behavior includes actual attempts, interrupted or aborted attempts, and any preparatory acts.
Time Frame	From first dose of study drug until a maximum of 168 days after last dose (225 days)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	8	6	6	6	6	4	6	6
Suicidal Ideation	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%
Suicidal Behavior	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants Who Developed Anti-erenumab Antibodies
Description	Participants who had a negative or no result at baseline and were antibody positive postbaseline. Blood samples were first tested for anti-erenumab binding antibodies, samples testing positive for binding antibodies were also tested for neutralizing antibodies.
Time Frame	From first dose of study drug until a maximum of 168 days after last dose (225 days)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	8	6	6	6	6	4	6	6
Binding antibodies	0 0%	1 16.7%	2 33.3%	0 0%	2 33.3%	0 0%	0 0%	0 0%
Neutralizing antibodies	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Erenumab
Description	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).
Time Frame	Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)

Outcome Measure Data

Analysis Population Description

All participants for whom at least 1 pharmacokinetic parameter or endpoint was adequately estimated and with available data at each time point.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	0	6	6	6	6	0	6	6
Day 1	2.15 (0.914)	6.26 (2.55)	13.8 (4.00)	24.9 (4.90)	1.76 (0.741)	11.0 (3.85)
Day 57	2.60 (0.952)	9.63 (3.60)	23.7 (7.89)	36.3 (6.18)	2.00 (0.552)	18.4 (5.98)

5. Secondary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of Erenumab
Description	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).
Time Frame	Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)

Outcome Measure Data

Analysis Population Description

All participants for whom at least 1 pharmacokinetic parameter or endpoint was adequately estimated and with available data at each time point.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	0	6	6	6	6	0	6	6
Day 1	4.0	4.0	5.9	6.9	6.9	11
Day 57	6.9	7.9	6.9	6.9	6.9	6.9

6. Secondary Outcome

Title	Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day)
Description	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).
Time Frame	Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)

Outcome Measure Data

Analysis Population Description

All participants for whom at least 1 pharmacokinetic parameter or endpoint was adequately estimated and with available data at each time point.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	0	6	6	6	6	0	6	6
Day 1	34.7 (13.1)	124 (49.2)	281 (89.1)	486 (57.8)	28.7 (11.0)	244 (86.2)
Day 57	49.5 (20.1)	216 (82.7)	476 (161)	760 (143)	37.9 (12.5)	417 (117)

7. Secondary Outcome

Title	Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Description	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).
Time Frame	Day 57 (assessed from predose to day 225))

Outcome Measure Data

Analysis Population Description

All participants who received erenumab and for whom at least 1 pharmacokinetic parameter or endpoint was adequately estimated and with available data at each time point.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	0	6	6	6	6	0	6	6
Mean (Standard Deviation) [day*μg/mL]	59.3 (27.8)	342 (144)	848 (376)	1410 (332)	45.0 (15.7)	773 (214)

8. Secondary Outcome

Title	Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow
Description	Inhibition of capsaicin-induced dermal blood flow (DBF) by erenumab was used to measure calcitonin gene-related peptide (CGRP) receptor antagonism. Capsaicin was applied at 2 sites on the volar surface of the participants' left or right forearms and a control mixture was applied to 1 site on the volar surface of either the participants' left or right forearm. Dermal blood flow was assessed by laser Doppler perfusion imaging and was done immediately before ('baseline') and 0.5 hours post-capsaicin on the surface of these 3 sites. Data reported are the least square geometric mean ratios for the post-capsaicin dermal blood flow to pre-capsaicin dermal blood flow. According to the protocol, not all cohorts had dermal blood flow measurements at all time points.
Time Frame	Baseline, Days 8, 57, 85, 113, 169 and 197

Outcome Measure Data

Analysis Population Description

All participants for whom at least 1 postdose capsaicin response measure was recorded. Measurement and analysis of dermal blood flow were not performed in the 280/210 cohort.

Arm/Group Title	Healthy: Placebo	Healthy: Erenumab 21 mg	Healthy: Erenumab 70 mg	Healthy: Erenumab 140 mg	Healthy: Erenumab 280/210 mg	Migraine: Placebo	Migraine: Erenumab 21 mg	Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.	Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.	Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.	Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
Measure Participants	6	6	6	6	0	4	6	6
Baseline	9.24 (1.20)	9.28 (1.21)	8.92 (1.20)	8.90 (1.22)	13.27 (1.37)	11.08 (1.29)	11.70 (1.28)
Day 8	8.53 (1.20)	1.76 (1.21)	2.46 (1.20)	1.75 (1.22)	13.20 (1.37)	2.64 (1.29)	1.64 (1.28)
Day 57	6.75 (1.20)	1.87 (1.21)	1.82 (1.20)	1.90 (1.22)	12.30 (1.37)	2.48 (1.29)	2.01 (1.28)
Day 85	8.61 (1.20)	2.71 (1.21)	1.63 (1.20)	1.80 (1.22)	13.33 (1.37)	2.40 (1.29)	2.08 (1.28)
Day 113	11.11 (1.33)	7.48 (1.21)	3.50 (1.51)	5.00 (1.29)
Day 169	9.72 (1.24)	10.06 (1.20)	5.78 (1.22)	14.78 (1.51)	4.64 (1.28)
Day 197	7.20 (1.33)	8.16 (1.22)	18.52 (1.51)	8.46 (1.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 21 mg
	Comments	Day 8: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-79.33
	Confidence Interval	(2-Sided) 95%; -87.54 to -65.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 70 mg
	Comments	Day 8: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-71.16
	Confidence Interval	(2-Sided) 95%; -82.67 to -52.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 140 mg
	Comments	Day 8: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-79.52
	Confidence Interval	(2-Sided) 95%; -88.29 to -64.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 21 mg
	Comments	Day 57: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-72.34
	Confidence Interval	(2-Sided) 95%; -83.32 to -54.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 70 mg
	Comments	Day 57: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-73.03
	Confidence Interval	(2-Sided) 95%; -83.79 to -55.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 140 mg
	Comments	Day 57: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-71.88
	Confidence Interval	(2-Sided) 95%; -83.93 to -50.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 21 mg
	Comments	Day 85: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-68.51
	Confidence Interval	(2-Sided) 95%; -81.01 to -47.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 70 mg
	Comments	Day 85: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-81.06
	Confidence Interval	(2-Sided) 95%; -88.62 to -68.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 140 mg
	Comments	Day 85: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-79.04
	Confidence Interval	(2-Sided) 95%; -88.02 to -63.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 21 mg
	Comments	Day 113: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-32.70
	Confidence Interval	(2-Sided) 95%; -65.71 to 32.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 70 mg
	Comments	Day 169: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	3.44
	Confidence Interval	(2-Sided) 95%; -40.78 to 80.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 140 mg
	Comments	Day 169: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.091
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-40.53
	Confidence Interval	(2-Sided) 95%; -67.50 to 8.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Healthy: Placebo, Healthy: Erenumab 140 mg
	Comments	Day 197: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	13.33
	Confidence Interval	(2-Sided) 95%; -44.39 to 130.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 21 mg
	Comments	Day 8: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-80.02
	Confidence Interval	(2-Sided) 95%; -91.53 to -52.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 140 mg
	Comments	Day 8: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-87.60
	Confidence Interval	(2-Sided) 95%; -94.53 to -71.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 21 mg
	Comments	Day 57: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Rratio
	Estimated Value	-79.81
	Confidence Interval	(2-Sided) 95%; -91.44 to -52.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 140 mg
	Comments	Day 57: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-83.66
	Confidence Interval	(2-Sided) 95%; -92.79 to -62.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 21 mg
	Comments	Day 85: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-81.97
	Confidence Interval	(2-Sided) 95%; -92.35 to -57.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 140 mg
	Comments	Day 85: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-84.39
	Confidence Interval	(2-Sided) 95%; -93.12 to -64.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 21 mg
	Comments	Day 113: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	43.10
	Confidence Interval	(2-Sided) 95%; -47.06 to 286.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 140 mg
	Comments	Day 169: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-68.58
	Confidence Interval	(2-Sided) 95%; -88.02 to -17.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Migraine: Placebo, Migraine: Erenumab 140 mg
	Comments	Day 197: A repeated measures ANCOVA was performed for the ratio of blood flow measures at 30 minutes post capsaicin challenge to pre capsaicin challenge. The model included treatment, day, and the treatment by day interaction as independent variables, and both the 0 minute pre-capsaicin blood flow measure as well as the day 0, 30-minute post-capsaicin blood flow measures on day -1 .
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Geometric Mean Ratio
	Estimated Value	-54.32
	Confidence Interval	(2-Sided) 95%; -82.58 to 19.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From first dose of study drug until a maximum of 168 days after last dose (225 days).
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Healthy: Placebo		Healthy: Erenumab 21 mg		Healthy: Erenumab 70 mg		Healthy: Erenumab 140 mg		Healthy: Erenumab 280/210 mg		Migraine: Placebo		Migraine: Erenumab 21 mg		Migraine: Erenumab 140 mg
Arm/Group Description	Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57.		Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.		Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57.		Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.		Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57.		Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57.		Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57.		Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57.
All Cause Mortality
	Healthy: Placebo		Healthy: Erenumab 21 mg		Healthy: Erenumab 70 mg		Healthy: Erenumab 140 mg		Healthy: Erenumab 280/210 mg		Migraine: Placebo		Migraine: Erenumab 21 mg		Migraine: Erenumab 140 mg
	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)
Serious Adverse Events
	Healthy: Placebo		Healthy: Erenumab 21 mg		Healthy: Erenumab 70 mg		Healthy: Erenumab 140 mg		Healthy: Erenumab 280/210 mg		Migraine: Placebo		Migraine: Erenumab 21 mg		Migraine: Erenumab 140 mg
	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	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Polyarthritis	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Psychiatric disorders
Depression	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Suicidal ideation	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Other (Not Including Serious) Adverse Events
	Healthy: Placebo		Healthy: Erenumab 21 mg		Healthy: Erenumab 70 mg		Healthy: Erenumab 140 mg		Healthy: Erenumab 280/210 mg		Migraine: Placebo		Migraine: Erenumab 21 mg		Migraine: Erenumab 140 mg
	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	5/8 (62.5%)		6/6 (100%)		6/6 (100%)		6/6 (100%)		4/6 (66.7%)		4/4 (100%)		6/6 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Eosinophilia	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Leukopenia	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Neutropenia	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Abdominal distension	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Abdominal pain	1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Abdominal pain upper	1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Dental caries	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Diarrhoea	0/8 (0%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		1/6 (16.7%)
Dyspepsia	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Mouth ulceration	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Nausea	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Paraesthesia oral	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Tongue discolouration	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
General disorders
Fatigue	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		2/6 (33.3%)
Influenza like illness	2/8 (25%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Injection site haemorrhage	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Injection site pain	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Local swelling	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Malaise	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Pyrexia	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Immune system disorders
Seasonal allergy	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Infections and infestations
Bronchitis	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Gastroenteritis	1/8 (12.5%)		1/6 (16.7%)		3/6 (50%)		0/6 (0%)		1/6 (16.7%)		1/4 (25%)		0/6 (0%)		1/6 (16.7%)
Gingivitis	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Influenza	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Laryngitis	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Nasopharyngitis	0/8 (0%)		2/6 (33.3%)		2/6 (33.3%)		3/6 (50%)		0/6 (0%)		0/4 (0%)		3/6 (50%)		3/6 (50%)
Sinusitis	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Upper respiratory tract infection	1/8 (12.5%)		2/6 (33.3%)		0/6 (0%)		3/6 (50%)		2/6 (33.3%)		0/4 (0%)		1/6 (16.7%)		1/6 (16.7%)
Injury, poisoning and procedural complications
Concussion	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Joint dislocation	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Tooth fracture	1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Investigations
Blood glucose increased	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Blood immunoglobulin E increased	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Neutrophil count decreased	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Back pain	1/8 (12.5%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		1/6 (16.7%)
Flank pain	0/8 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Musculoskeletal pain	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Musculoskeletal stiffness	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Myalgia	0/8 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		1/6 (16.7%)
Neck pain	0/8 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Osteochondrosis	0/8 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Polyarthritis	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Nervous system disorders
Dizziness postural	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Headache	1/8 (12.5%)		0/6 (0%)		2/6 (33.3%)		3/6 (50%)		2/6 (33.3%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Hypoaesthesia	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Paraesthesia	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		1/6 (16.7%)
Psychiatric disorders
Depressed mood	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Depression	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Insomnia	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)
Renal and urinary disorders
Haematuria	0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		3/6 (50%)		2/4 (50%)		2/6 (33.3%)		1/6 (16.7%)
Leukocyturia	0/8 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)		0/4 (0%)		3/6 (50%)		2/6 (33.3%)
Reproductive system and breast disorders
Dysmenorrhoea	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)
Epistaxis	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)
Oropharyngeal pain	1/8 (12.5%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		3/6 (50%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Blister	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Hyperhidrosis	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Pruritus	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)
Rash	0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)

Limitations/Caveats

[Not Specified]

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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.