Migraine
Conditions
Keywords
Migraine
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.
Interventions
DRUGErenumab
Administered by subcutaneous injection once a month
DRUGPlacebo
Administered by subcutaneous injection once a month
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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. |
| 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). |
| 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). |
Countries
Belgium
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Healthy: Placebo Healthy participants received placebo subcutaneous injection on Days 1, 29, and 57. | 8 |
| Healthy: Erenumab 21 mg Healthy participants received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57. | 6 |
| Healthy: Erenumab 70 mg Healthy participants received 70 mg erenumab by subcutaneous injection on days 1, 29 and 57. | 6 |
| Healthy: Erenumab 140 mg Healthy participants received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57. | 6 |
| Healthy: Erenumab 280/210 mg Healthy participants received 280 mg erenumab by subcutaneous injection on day 1, and 210 mg erenumab on days 29 and 57. | 6 |
| Migraine: Placebo Participants with migraine received placebo by subcutaneous injection on days 1, 29 and 57. | 4 |
| Migraine: Erenumab 21 mg Participants with migraine received 21 mg erenumab by subcutaneous injection on days 1, 29 and 57. | 6 |
| Migraine: Erenumab 140 mg Participants with migraine received 140 mg erenumab by subcutaneous injection on days 1, 29 and 57. | 6 |
| Total | 48 |
Baseline characteristics
| Characteristic | Healthy: Placebo | Healthy: Erenumab 21 mg | Healthy: Erenumab 70 mg | Healthy: Erenumab 140 mg | Healthy: Erenumab 280/210 mg | Total | Migraine: Placebo | Migraine: Erenumab 21 mg | Migraine: Erenumab 140 mg |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Healthy Participants | 32.1 years STANDARD_DEVIATION 13 | 26.3 years STANDARD_DEVIATION 5.7 | 33.3 years STANDARD_DEVIATION 14.1 | 29.8 years STANDARD_DEVIATION 8.6 | 39.0 years STANDARD_DEVIATION 13.8 | 32.1 years STANDARD_DEVIATION 11.6 | — | — | — |
| Age, Continuous Migraine Participants | — | — | — | — | — | 32.9 years STANDARD_DEVIATION 11.3 | 37.0 years STANDARD_DEVIATION 11.9 | 31.7 years STANDARD_DEVIATION 11 | 31.3 years STANDARD_DEVIATION 12.6 |
| Race/Ethnicity, Customized White | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 48 Participants | 4 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 15 Participants | 3 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 33 Participants | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 8 | 6 / 6 | 6 / 6 | 6 / 6 | 4 / 6 | 4 / 4 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 1 / 6 |
Outcome results
Primary
Number of Participants Who Developed Anti-erenumab Antibodies
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)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 0 Participants |
| Healthy: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 1 Participants |
| Healthy: Erenumab 21 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 1 Participants |
| Healthy: Erenumab 70 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 2 Participants |
| Healthy: Erenumab 70 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 2 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 0 Participants |
| Migraine: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 0 Participants |
| Migraine: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibodies | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibodies | 0 Participants |
Primary
Number of Participants With Adverse Events
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)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy: Placebo | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | Serious adverse event | 1 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 1 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 1 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 1 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 2 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 3 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | Any adverse event | 4 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | Any adverse event | 4 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | Serious adverse event | 1 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
Primary
Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
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)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy: Placebo | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Healthy: Placebo | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Healthy: Erenumab 21 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Healthy: Erenumab 70 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Healthy: Erenumab 140 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Healthy: Erenumab 280/210 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Migraine: Placebo | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Migraine: Placebo | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Migraine: Erenumab 21 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 1 Participants |
| Migraine: Erenumab 140 mg | Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
Secondary
Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day)
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)
Population: All participants for whom at least 1 pharmacokinetic parameter or endpoint was adequately estimated and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy: Erenumab 21 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 1 | 34.7 day*μg/mL | Standard Deviation 13.1 |
| Healthy: Erenumab 21 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 57 | 49.5 day*μg/mL | Standard Deviation 20.1 |
| Healthy: Erenumab 70 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 1 | 124 day*μg/mL | Standard Deviation 49.2 |
| Healthy: Erenumab 70 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 57 | 216 day*μg/mL | Standard Deviation 82.7 |
| Healthy: Erenumab 140 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 1 | 281 day*μg/mL | Standard Deviation 89.1 |
| Healthy: Erenumab 140 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 57 | 476 day*μg/mL | Standard Deviation 161 |
| Healthy: Erenumab 280/210 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 1 | 486 day*μg/mL | Standard Deviation 57.8 |
| Healthy: Erenumab 280/210 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 57 | 760 day*μg/mL | Standard Deviation 143 |
| Migraine: Erenumab 21 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 1 | 28.7 day*μg/mL | Standard Deviation 11 |
| Migraine: Erenumab 21 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 57 | 37.9 day*μg/mL | Standard Deviation 12.5 |
| Migraine: Erenumab 140 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 1 | 244 day*μg/mL | Standard Deviation 86.2 |
| Migraine: Erenumab 140 mg | Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Day 57 | 417 day*μg/mL | Standard Deviation 117 |
Secondary
Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).
Time frame: Day 57 (assessed from predose to day 225))
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy: Erenumab 21 mg | Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 59.3 day*μg/mL | Standard Deviation 27.8 |
| Healthy: Erenumab 70 mg | Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 342 day*μg/mL | Standard Deviation 144 |
| Healthy: Erenumab 140 mg | Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 848 day*μg/mL | Standard Deviation 376 |
| Healthy: Erenumab 280/210 mg | Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 1410 day*μg/mL | Standard Deviation 332 |
| Migraine: Erenumab 21 mg | Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 45.0 day*μg/mL | Standard Deviation 15.7 |
| Migraine: Erenumab 140 mg | Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 773 day*μg/mL | Standard Deviation 214 |
Secondary
Maximum Observed Serum Concentration (Cmax) of Erenumab
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)
Population: All participants for whom at least 1 pharmacokinetic parameter or endpoint was adequately estimated and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy: Erenumab 21 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 57 | 2.60 μg/mL | Standard Deviation 0.952 |
| Healthy: Erenumab 21 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 1 | 2.15 μg/mL | Standard Deviation 0.914 |
| Healthy: Erenumab 70 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 1 | 6.26 μg/mL | Standard Deviation 2.55 |
| Healthy: Erenumab 70 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 57 | 9.63 μg/mL | Standard Deviation 3.6 |
| Healthy: Erenumab 140 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 1 | 13.8 μg/mL | Standard Deviation 4 |
| Healthy: Erenumab 140 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 57 | 23.7 μg/mL | Standard Deviation 7.89 |
| Healthy: Erenumab 280/210 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 57 | 36.3 μg/mL | Standard Deviation 6.18 |
| Healthy: Erenumab 280/210 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 1 | 24.9 μg/mL | Standard Deviation 4.9 |
| Migraine: Erenumab 21 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 1 | 1.76 μg/mL | Standard Deviation 0.741 |
| Migraine: Erenumab 21 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 57 | 2.00 μg/mL | Standard Deviation 0.552 |
| Migraine: Erenumab 140 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 57 | 18.4 μg/mL | Standard Deviation 5.98 |
| Migraine: Erenumab 140 mg | Maximum Observed Serum Concentration (Cmax) of Erenumab | Day 1 | 11.0 μg/mL | Standard Deviation 3.85 |
Secondary
Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow
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
Population: 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 | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 8 | 8.53 ratio | Standard Error 1.2 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 57 | 6.75 ratio | Standard Error 1.2 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 8.61 ratio | Standard Error 1.2 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 113 | 11.11 ratio | Standard Error 1.33 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 197 | 7.20 ratio | Standard Error 1.33 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 169 | 9.72 ratio | Standard Error 1.24 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Baseline | 9.24 ratio | Standard Error 1.2 |
| Healthy: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 2.71 ratio | Standard Error 1.21 |
| Healthy: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 57 | 1.87 ratio | Standard Error 1.21 |
| Healthy: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Baseline | 9.28 ratio | Standard Error 1.21 |
| Healthy: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 113 | 7.48 ratio | Standard Error 1.21 |
| Healthy: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 8 | 1.76 ratio | Standard Error 1.21 |
| Healthy: Erenumab 70 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 169 | 10.06 ratio | Standard Error 1.2 |
| Healthy: Erenumab 70 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Baseline | 8.92 ratio | Standard Error 1.2 |
| Healthy: Erenumab 70 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 8 | 2.46 ratio | Standard Error 1.2 |
| Healthy: Erenumab 70 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 57 | 1.82 ratio | Standard Error 1.2 |
| Healthy: Erenumab 70 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 1.63 ratio | Standard Error 1.2 |
| Healthy: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Baseline | 8.90 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 1.80 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 169 | 5.78 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 197 | 8.16 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 57 | 1.90 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 8 | 1.75 ratio | Standard Error 1.22 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 8 | 13.20 ratio | Standard Error 1.37 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 57 | 12.30 ratio | Standard Error 1.37 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 197 | 18.52 ratio | Standard Error 1.51 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 13.33 ratio | Standard Error 1.37 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Baseline | 13.27 ratio | Standard Error 1.37 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 113 | 3.50 ratio | Standard Error 1.51 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 169 | 14.78 ratio | Standard Error 1.51 |
| Migraine: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 8 | 2.64 ratio | Standard Error 1.29 |
| Migraine: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Baseline | 11.08 ratio | Standard Error 1.29 |
| Migraine: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 57 | 2.48 ratio | Standard Error 1.29 |
| Migraine: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 2.40 ratio | Standard Error 1.29 |
| Migraine: Erenumab 21 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 113 | 5.00 ratio | Standard Error 1.29 |
| Migraine: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Baseline | 11.70 ratio | Standard Error 1.28 |
| Migraine: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 2.08 ratio | Standard Error 1.28 |
| Migraine: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 8 | 1.64 ratio | Standard Error 1.28 |
| Migraine: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 197 | 8.46 ratio | Standard Error 1.28 |
| Migraine: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 57 | 2.01 ratio | Standard Error 1.28 |
| Migraine: Erenumab 140 mg | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 169 | 4.64 ratio | Standard Error 1.28 |
Comparison: 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 .p-value: <0.00195% CI: [-87.54, -65.73]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-82.67, -52]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-88.29, -64.17]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-83.32, -54.13]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-83.79, -55.11]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-83.93, -50.82]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-81.01, -47.78]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-88.62, -68.49]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-88.02, -63.34]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.2595% CI: [-65.71, 32.1]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.995% CI: [-40.78, 80.66]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.09195% CI: [-67.5, 8.82]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.7395% CI: [-44.39, 130.94]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.00195% CI: [-91.53, -52.87]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-94.53, -71.88]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.00195% CI: [-91.44, -52.37]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-92.79, -62.95]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-92.35, -57.46]Repeated Measures ANCOVA
Comparison: 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 .p-value: <0.00195% CI: [-93.12, -64.6]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.4795% CI: [-47.06, 286.83]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.0295% CI: [-88.02, -17.63]Repeated Measures ANCOVA
Comparison: 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 .p-value: 0.1195% CI: [-82.58, 19.75]Repeated Measures ANCOVA
Secondary
Time to Maximum Observed Concentration (Tmax) of Erenumab
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)
Population: All participants for whom at least 1 pharmacokinetic parameter or endpoint was adequately estimated and with available data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy: Erenumab 21 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 57 | 6.9 days |
| Healthy: Erenumab 21 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 1 | 4.0 days |
| Healthy: Erenumab 70 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 1 | 4.0 days |
| Healthy: Erenumab 70 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 57 | 7.9 days |
| Healthy: Erenumab 140 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 57 | 6.9 days |
| Healthy: Erenumab 140 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 1 | 5.9 days |
| Healthy: Erenumab 280/210 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 57 | 6.9 days |
| Healthy: Erenumab 280/210 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 1 | 6.9 days |
| Migraine: Erenumab 21 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 1 | 6.9 days |
| Migraine: Erenumab 21 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 57 | 6.9 days |
| Migraine: Erenumab 140 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 1 | 11 days |
| Migraine: Erenumab 140 mg | Time to Maximum Observed Concentration (Tmax) of Erenumab | Day 57 | 6.9 days |