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 single subcutaneous (SC) or intravenous (IV) doses in healthy participants and migraine patients as well as to characterize the effect of erenumab on the capsaicin-induced increase in dermal blood flow after single SC or IV doses in healthy participants and migraine patients.
Detailed description
This study was a single-dose, double-blind, placebo-controlled, sequential dose escalation study in which participants were to be enrolled into 8 cohorts. In Part 1 healthy participants were randomized in a 3:1 ratio (erenumab:placebo) into 6 cohorts: 5 cohorts received the investigational product (IP) as an SC administration and 1 cohort received it as an IV administration. In Part 2 a total of 12 migraine patients were randomized in a 1:1 ratio (erenumab:placebo) in cohort 7. An additional 8 migraine patients could have been enrolled and randomized in a 3:1 ratio in the optional cohort 8, however this cohort was not enrolled.
Interventions
DRUGErenumab
Administered by subcutaneous injection or intravenous injection
DRUGPlacebo
Administered by subcutaneous injection or intravenous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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 between 18 and 45 years of age, or 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 the initial dose of study drug up to 155 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 Who Developed Anti-erenumab Antibodies | Baseline and up to 155 days postdose | 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 Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | Predose to 155 days postdose | — |
| Maximum Observed Concentration (Cmax) of Erenumab | Predose to 155 days postdose | — |
| Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Days 4, 15, 29, 43, 64, 85, 99, 127, and end of study (defined as day 43 for the 1 mg, 7 mg and 21 mg erenumab cohorts, day 99 for the 70 mg erenumab cohort, day 127 for the 140 mg erenumab cohorts and day 155 for the 210 mg erenumab cohort). | 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. |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | Predose to 155 days postdose | — |
| Time to Maximum Observed Concentration (Tmax) of Erenumab | Predose to 155 days postdose | — |
Countries
Belgium
Participant flow
Recruitment details
This study was conducted at a single center in Belgium from March 2012 to March 2013. The study enrolled healthy participants (Part 1) and participants who had migraines for at least 6 months and at least 3 migraine attacks per month in the last 3 months (Part 2).
Pre-assignment details
Healthy participants were randomized in a 3:1 ratio to erenumab or placebo within each dose cohort. Migraine participants were randomized in a 1:1 ratio to erenumab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Healthy: Placebo Healthy participants received a single dose of matching placebo administered by subcutaneous (SC) or intravenous (IV) injection. | 12 |
| Healthy: Erenumab 1 mg SC Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | 3 |
| Healthy: Erenumab 7 mg SC Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | 3 |
| Healthy: Erenumab 21 mg SC Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | 6 |
| Healthy: Erenumab 70 mg SC Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | 6 |
| Healthy: Erenumab 140 mg SC Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | 6 |
| Healthy: Erenumab 140 mg IV Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | 6 |
| Healthy: Erenumab 210 mg SC Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | 6 |
| Migraine: Placebo Participants with migraine received a single dose of placebo administered by subcutaneous injection. | 6 |
| Migraine: Erenumab 140 mg SC Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. | 6 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Total | Migraine: Placebo | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Healthy Participants | 28.6 years STANDARD_DEVIATION 6.1 | 22.0 years STANDARD_DEVIATION 1.7 | 26.0 years STANDARD_DEVIATION 7.9 | 25.7 years STANDARD_DEVIATION 6.9 | 27.5 years STANDARD_DEVIATION 6.6 | 28.0 years STANDARD_DEVIATION 8.5 | 31.0 years STANDARD_DEVIATION 8.1 | 26.2 years STANDARD_DEVIATION 7 | 27.4 years STANDARD_DEVIATION 6.8 | — | — |
| Age, Continuous Migraine Participants | — | — | — | — | — | — | — | — | 26.2 years STANDARD_DEVIATION 9.6 | 28.5 years STANDARD_DEVIATION 12.6 | 23.8 years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 3 Participants | 3 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 59 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 3 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 59 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 12 Participants | 3 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 51 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 | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 12 | 2 / 3 | 1 / 3 | 6 / 6 | 5 / 6 | 5 / 6 | 5 / 6 | 6 / 6 | 5 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 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: Baseline and up to 155 days postdose
Population: All participants who received study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Healthy: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 1 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Migraine: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Migraine: Placebo | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Binding antibody positive | 0 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants Who Developed Anti-erenumab Antibodies | Neutralizing antibody positive | 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 the initial dose of study drug up to 155 days.
Population: All participants who received study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy: Placebo | Number of Participants With Adverse Events | Any adverse event | 10 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | Treatment-related adverse events | 4 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Placebo | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants With Adverse Events | Any adverse event | 2 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 1 mg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants With Adverse Events | Any adverse event | 1 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 7 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 21 mg SC | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 70 mg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 140 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Healthy: Erenumab 140 mg IV | Number of Participants With Adverse Events | Treatment-related adverse events | 2 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 4 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Healthy: Erenumab 210 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | Any adverse event | 5 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 | Treatment-related adverse events | 0 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 from study | 0 Participants |
| Migraine: Placebo | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Migraine: Erenumab 140 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab
Time frame: Predose to 155 days postdose
Population: All participants who received erenumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy: Erenumab 1 mg SC | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | 4.13 days*µg/mL | Standard Deviation 2.04 |
| Healthy: Erenumab 7 mg SC | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | 24.5 days*µg/mL | Standard Deviation 17 |
| Healthy: Erenumab 21 mg SC | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | 174 days*µg/mL | Standard Deviation 78.6 |
| Healthy: Erenumab 70 mg SC | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | 333 days*µg/mL | Standard Deviation 57.9 |
| Healthy: Erenumab 140 mg SC | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | 615 days*µg/mL | Standard Deviation 112 |
| Healthy: Erenumab 140 mg IV | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | 653 days*µg/mL | Standard Deviation 222 |
| Healthy: Erenumab 210 mg SC | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab | 367 days*µg/mL | Standard Deviation 103 |
p-value: 0.550690% CI: [0.9, 1.4]ANCOVA
Secondary
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab
Time frame: Predose to 155 days postdose
Population: All participants who received erenumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy: Placebo | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 0.0851 days*µg/mL | Standard Deviation 0.0169 |
| Healthy: Erenumab 1 mg SC | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 4.01 days*µg/mL | Standard Deviation 2.07 |
| Healthy: Erenumab 7 mg SC | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 23.5 days*µg/mL | Standard Deviation 15.5 |
| Healthy: Erenumab 21 mg SC | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 171 days*µg/mL | Standard Deviation 60.9 |
| Healthy: Erenumab 70 mg SC | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 332 days*µg/mL | Standard Deviation 57.9 |
| Healthy: Erenumab 140 mg SC | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 614 days*µg/mL | Standard Deviation 112 |
| Healthy: Erenumab 140 mg IV | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 652 days*µg/mL | Standard Deviation 221 |
| Healthy: Erenumab 210 mg SC | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab | 367 days*µg/mL | Standard Deviation 102 |
p-value: 0.548190% CI: [0.9, 1.4]ANCOVA
Secondary
Maximum Observed Concentration (Cmax) of Erenumab
Time frame: Predose to 155 days postdose
Population: All participants who received erenumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy: Placebo | Maximum Observed Concentration (Cmax) of Erenumab | 0.0077 µg/mL | Standard Deviation 0.00395 |
| Healthy: Erenumab 1 mg SC | Maximum Observed Concentration (Cmax) of Erenumab | 0.302 µg/mL | Standard Deviation 0.145 |
| Healthy: Erenumab 7 mg SC | Maximum Observed Concentration (Cmax) of Erenumab | 1.17 µg/mL | Standard Deviation 0.646 |
| Healthy: Erenumab 21 mg SC | Maximum Observed Concentration (Cmax) of Erenumab | 6.25 µg/mL | Standard Deviation 2.03 |
| Healthy: Erenumab 70 mg SC | Maximum Observed Concentration (Cmax) of Erenumab | 9.18 µg/mL | Standard Deviation 1.97 |
| Healthy: Erenumab 140 mg SC | Maximum Observed Concentration (Cmax) of Erenumab | 47.8 µg/mL | Standard Deviation 4.09 |
| Healthy: Erenumab 140 mg IV | Maximum Observed Concentration (Cmax) of Erenumab | 15.2 µg/mL | Standard Deviation 4.78 |
| Healthy: Erenumab 210 mg SC | Maximum Observed Concentration (Cmax) of Erenumab | 9.93 µg/mL | Standard Deviation 3.42 |
p-value: 0.759590% CI: [0.8, 1.4]ANCOVA
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: Days 4, 15, 29, 43, 64, 85, 99, 127, and end of study (defined as day 43 for the 1 mg, 7 mg and 21 mg erenumab cohorts, day 99 for the 70 mg erenumab cohort, day 127 for the 140 mg erenumab cohorts and day 155 for the 210 mg erenumab cohort).
Population: All participants for whom at least one post-dose capsaicin response measure was recorded.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 9.6 ratio | Standard Error 1.15 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 127 | 11.4 ratio | Standard Error 1.36 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 7.2 ratio | Standard Error 1.15 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 8.6 ratio | Standard Error 1.15 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 10.7 ratio | Standard Error 1.21 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 8.6 ratio | Standard Error 1.15 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 64 | 8.3 ratio | Standard Error 1.21 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 43 | 8.4 ratio | Standard Error 1.19 |
| Healthy: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 99 | 7.6 ratio | Standard Error 1.21 |
| Healthy: Erenumab 1 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 8.2 ratio | Standard Error 1.32 |
| Healthy: Erenumab 1 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 8.3 ratio | Standard Error 1.32 |
| Healthy: Erenumab 1 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 9.9 ratio | Standard Error 1.32 |
| Healthy: Erenumab 1 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 9.0 ratio | Standard Error 1.32 |
| Healthy: Erenumab 7 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 10.5 ratio | Standard Error 1.32 |
| Healthy: Erenumab 7 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 3.6 ratio | Standard Error 1.32 |
| Healthy: Erenumab 7 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 5.6 ratio | Standard Error 1.32 |
| Healthy: Erenumab 7 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 10.8 ratio | Standard Error 1.32 |
| Healthy: Erenumab 21 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 2.9 ratio | Standard Error 1.22 |
| Healthy: Erenumab 21 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 9.0 ratio | Standard Error 1.22 |
| Healthy: Erenumab 21 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 3.0 ratio | Standard Error 1.22 |
| Healthy: Erenumab 21 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 1.4 ratio | Standard Error 1.22 |
| Healthy: Erenumab 70 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 1.7 ratio | Standard Error 1.22 |
| Healthy: Erenumab 70 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 43 | 1.2 ratio | Standard Error 1.26 |
| Healthy: Erenumab 70 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 2.0 ratio | Standard Error 1.22 |
| Healthy: Erenumab 70 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 3.6 ratio | Standard Error 1.22 |
| Healthy: Erenumab 70 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 2.2 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 43 | 1.8 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 64 | 1.5 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 1.1 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 7.6 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 99 | 5.1 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 1.4 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 1.3 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 4.6 ratio | Standard Error 1.26 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 43 | 2.0 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 1.4 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 1.7 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 1.6 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 64 | 2.2 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 3.9 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 99 | 5.9 ratio | Standard Error 1.22 |
| Healthy: Erenumab 140 mg IV | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 8.3 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 64 | 2.3 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 99 | 4.3 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 1.9 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 8.8 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 1.9 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 127 | 9.1 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 2.6 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 2.2 ratio | Standard Error 1.22 |
| Healthy: Erenumab 210 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 43 | 2.1 ratio | Standard Error 1.22 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 12.4 ratio | Standard Error 1.2 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 12.0 ratio | Standard Error 1.2 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 11.9 ratio | Standard Error 1.2 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 43 | 12.0 ratio | Standard Error 1.2 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 64 | 12.4 ratio | Standard Error 1.2 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 13.1 ratio | Standard Error 1.2 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 12.0 ratio | Standard Error 1.2 |
| Migraine: Placebo | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 99 | 12.2 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 99 | 10.2 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 85 | 7.4 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 29 | 1.8 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 64 | 2.0 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 15 | 2.1 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 4 | 2.0 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Day 43 | 2.1 ratio | Standard Error 1.2 |
| Migraine: Erenumab 140 mg SC | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | End of study | 9.8 ratio | Standard Error 1.2 |
Secondary
Time to Maximum Observed Concentration (Tmax) of Erenumab
Time frame: Predose to 155 days postdose
Population: All participants who received erenumab
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy: Placebo | Time to Maximum Observed Concentration (Tmax) of Erenumab | 4.0 days |
| Healthy: Erenumab 1 mg SC | Time to Maximum Observed Concentration (Tmax) of Erenumab | 7.0 days |
| Healthy: Erenumab 7 mg SC | Time to Maximum Observed Concentration (Tmax) of Erenumab | 7.0 days |
| Healthy: Erenumab 21 mg SC | Time to Maximum Observed Concentration (Tmax) of Erenumab | 6.0 days |
| Healthy: Erenumab 70 mg SC | Time to Maximum Observed Concentration (Tmax) of Erenumab | 5.5 days |
| Healthy: Erenumab 140 mg SC | Time to Maximum Observed Concentration (Tmax) of Erenumab | 0.069 days |
| Healthy: Erenumab 140 mg IV | Time to Maximum Observed Concentration (Tmax) of Erenumab | 8.5 days |
| Healthy: Erenumab 210 mg SC | Time to Maximum Observed Concentration (Tmax) of Erenumab | 11 days |