Study to Evaluate the Effect of Erenumab on Blood Pressure When Given Concomitantly With Subcutaneous Sumatriptan

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02741310
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.6
• Patients Per Site Per Month: 6.1

Study Details

Study Description

Brief Summary

The primary objective of this study was to assess the effects of subcutaneous sumatriptan alone and the effects of a single dose of erenumab (AMG 334) intravenous (IV) and sumatriptan concomitant therapy on resting blood pressure in healthy adults.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: Placebo; Drug: Sumatriptan; Drug: Erenumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 1, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Single-Dose Study to Evaluate the Effect on Blood Pressure of AMG 334 Given Concomitantly With Subcutaneous Sumatriptan (Imitrex™) in Healthy Subjects
• Actual Study Start Date: Feb 22, 2016
• Actual Primary Completion Date: Aug 11, 2016
• Actual Study Completion Date: Aug 11, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous sumatriptan on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg subcutaneous sumatriptan on day 5 (Part 2).	Drug: Placebo; Administered by intravenous infusion; Drug: Sumatriptan; Administered by two 6 mg subcutaneous injections 1 hour apart on day 2 and day 5; Other Names: Imitrex™
Experimental: Erenumab Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous sumatriptan on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg subcutaneous sumatriptan on day 5 (Part 2).	Drug: Placebo; Administered by intravenous infusion; Drug: Sumatriptan; Administered by two 6 mg subcutaneous injections 1 hour apart on day 2 and day 5; Other Names: Imitrex™ ; Drug: Erenumab; Administered by intravenous infusion; Other Names: AMG 334 Aimovig™

Outcome Measures

Primary Outcome Measures

1. Time-weighted Averages of Mean Arterial Pressure [Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing.]

   Mean arterial pressure (MAP) is the average arterial pressure during a single cardiac cycle. MAP was calculated as diastolic blood pressure (DBP) + 0.33 * (systolic blood pressure [SBP]-DBP). Individual time-weighted average in MAP were calculated as area under the measurement-time curve from predose through 2.5 hours of MAP divided by the time period over which the measurements were made (ie, AUCmap0-2.5 hr /2.5 hours). Data were analyzed using a linear mixed effects regression model with fixed effects for treatment and period and random effect for subject; Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

Secondary Outcome Measures

1. Number of Participants With Adverse Events [From the first dose of study drug (sumatriptan, placebo or erenumab) until 84 days after the last dose (89 days). Part 1 includes AEs from day 1 to predose on day 4 and Part 2 includes AEs from day 4 through day 89.]

   Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and according to the following: Grade 1 = Mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate, minimal, local or noninvasive intervention indicated; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences, urgent intervention indicated; Grade 5 = Death related to AE.

2. Area Under the Concentration-time Curve From Time 0 to 6 Hours for Sumatriptan [Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.]

   Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Area under the plasma concentration-time curve from time 0 to 6 hours post dose (AUC6hr) after the 2nd 6 mg dose of sumatriptan was estimated using the linear trapezoidal method. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ; 0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUC6hr was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

3. Area Under the Concentration-time Curve From Time 0 to Infinity for Sumatriptan [Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.]

   Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. The area under the plasma concentration-time curve from time 0 to infinity (AUCinf) after the 2nd 6 mg dose of sumatriptan was estimated as the sum of AUClast and Clast/λz where Clast is the last observed concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUCinf was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

4. Maximum Observed Plasma Concentration (Cmax) of Sumatriptan [Day 2 and day 5 at predose, 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.]

   Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed maximum observed plasma concentration (Cmax) was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

5. Number of Participants Who Developed Anti-erenumab Antibodies [Baseline and day 89]

   Two validated assays were used to detect the presence of anti-erenumab antibodies. All samples were first tested in an electrochemiluminescence-based bridging assay to detect antibodies capable of binding to erenumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Binding/neutralizing antibody positive is defined as participants with an antibody positive postbaseline results and with a negative or no result at baseline.

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 ≥ 18 to ≤ 55 years old

• Good general health

• Laboratory results within range

• Other Inclusion Criteria May Apply

Exclusion Criteria:

• Female subjects pregnant or breastfeeding

• An unstable medical condition

• History of cancer

• Active liver disease

• Positive Hepatitis B or Hepatitis C

• Unwilling or unable to limit alcohol consumption

• Unable to refrain from strenuous exercise

• Other Exclusion Criteria May Apply

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, Herbots M, Kubo Y, Lee E, Eisele O, Vargas G, Gabriel K. Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers. Cephalalgia. 2019 Jan;39(1):100-110. doi: 10.1177/0333102418776017. Epub 2018 May 21.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02741310
• Other Study ID Numbers: 20140255; 2015-004537-28
• First Posted: Apr 18, 2016
• Last Update Posted: Apr 2, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Sumatriptan; Erenumab

Study Results

Participant Flow

Recruitment Details	This study was conducted at 1 center in Belgium; participants were enrolled from 22 February 2016 to 11 May 2016.
Pre-assignment Detail	Eligible participants were randomized on day 1 to receive either erenumab or matching placebo in a 2:1 allocation ratio.

Arm/Group Title	Group A: Placebo + Sumatriptan	Group B: Erenumab + Sumatriptan
Arm/Group Description	Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).
Period Title: Overall Study
STARTED	12	22
COMPLETED	10	20
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Group A: Placebo + Sumatriptan	Group B: Erenumab + Sumatriptan	Total
Arm/Group Description	Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Total of all reporting groups
Overall Participants	12	22	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.3 (8.6)	29.1 (10.3)	28.5 (9.6)
Age, Customized (Count of Participants)
18 - 24 years	6 50%	9 40.9%	15 44.1%
25 - 55 years	6 50%	13 59.1%	19 55.9%
Sex: Female, Male (Count of Participants)
Female	4 33.3%	6 27.3%	10 29.4%
Male	8 66.7%	16 72.7%	24 70.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 8.3%	0 0%	1 2.9%
Not Hispanic or Latino	11 91.7%	22 100%	33 97.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Black (or African American)	0 0%	1 4.5%	1 2.9%
Multiple	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
White	12 100%	21 95.5%	33 97.1%

Outcome Measures

1. Primary Outcome

Title	Time-weighted Averages of Mean Arterial Pressure
Description	Mean arterial pressure (MAP) is the average arterial pressure during a single cardiac cycle. MAP was calculated as diastolic blood pressure (DBP) + 0.33 * (systolic blood pressure [SBP]-DBP). Individual time-weighted average in MAP were calculated as area under the measurement-time curve from predose through 2.5 hours of MAP divided by the time period over which the measurements were made (ie, AUCmap0-2.5 hr /2.5 hours). Data were analyzed using a linear mixed effects regression model with fixed effects for treatment and period and random effect for subject; Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).
Time Frame	Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and with available data.

Arm/Group Title	Sumatriptan Alone	Erenumab + Sumatriptan
Arm/Group Description	All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	All participants who received erenumab plus sumatriptan (Group B, Part 2)
Measure Participants	34	20
Least Squares Mean (Standard Error) [mmHg]	87.40 (0.98)	87.36 (1.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sumatriptan Alone, Erenumab + Sumatriptan
	Comments	A linear mixed effects regression analysis was performed to assess if the time-weighted average in MAP for erenumab with sumatriptan is similar to sumatriptan alone. A two-sided 90% confidence interval (equivalent to a one-sided upper 95% CI) for the mean treatment difference was calculated using a linear mixed-effects model with fixed effects for treatment and period and a random effect for subject.
	Type of Statistical Test	Other
	Comments	The clinical hypothesis was that there would be no clinically meaningful difference between the blood pressure effects of sumatriptan alone and the effects of a single dose of erenumab IV and sumatriptan concomitant therapy. A clinically meaningful difference was defined as the upper bound of the 90% confidence interval (CI) of treatment difference between erenumab IV and sumatriptan compared to sumatriptan alone being ≥ 5 mmHg on the time-weighted scale resting MAP.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 90%; -2.16 to 2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and according to the following: Grade 1 = Mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate, minimal, local or noninvasive intervention indicated; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences, urgent intervention indicated; Grade 5 = Death related to AE.
Time Frame	From the first dose of study drug (sumatriptan, placebo or erenumab) until 84 days after the last dose (89 days). Part 1 includes AEs from day 1 to predose on day 4 and Part 2 includes AEs from day 4 through day 89.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab).

Arm/Group Title	Part 1 Group A: Placebo + Sumatriptan	Part 1 Group B: Placebo + Sumatriptan	Part 2 Group A: Placebo + Sumatriptan	Part 2 Group B: Erenumab + Sumatriptan
Arm/Group Description	In Part 1 participants in Group A received a placebo IV infusion on day 1 then 12 mg SC sumatriptan on day 2.	In Part 1 participants in Group B received a placebo IV infusion on day 1 then 12 mg SC sumatriptan on day 2.	In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.	In Part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.
Measure Participants	12	22	12	22
Any adverse event	11 91.7%	19 86.4%	9 26.5%	17 NaN
Adverse event ≥ grade 2	1 8.3%	0 0%	0 0%	3 NaN
Adverse event ≥ grade 3	0 0%	0 0%	0 0%	0 NaN
Adverse event ≥ grade 4	0 0%	0 0%	0 0%	0 NaN
Serious adverse events	0 0%	0 0%	0 0%	0 NaN
AE leading to discontinuation of study drug	2 16.7%	2 9.1%	0 0%	0 NaN
Fatal adverse events	0 0%	0 0%	0 0%	0 NaN

3. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to 6 Hours for Sumatriptan
Description	Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Area under the plasma concentration-time curve from time 0 to 6 hours post dose (AUC6hr) after the 2nd 6 mg dose of sumatriptan was estimated using the linear trapezoidal method. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ; 0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUC6hr was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).
Time Frame	Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter.

Arm/Group Title	Sumatriptan Alone	Erenumab + Sumatriptan
Arm/Group Description	All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	All participants who received erenumab plus sumatriptan (Group B, Part 2)
Measure Participants	30	20
Geometric Least Squares Mean (Standard Error) [hr*ng/mL]	133.33 (1.03)	130.59 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sumatriptan Alone, Erenumab + Sumatriptan
	Comments	The mean for each treatment was compared using a linear mixed effects model with group A (sumatriptan alone) as the reference treatment group. The linear mixed effects model included treatment (erenumab with sumatriptan vs sumatriptan alone) and period as a fixed effect and subject as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 90%; 0.93 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to Infinity for Sumatriptan
Description	Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. The area under the plasma concentration-time curve from time 0 to infinity (AUCinf) after the 2nd 6 mg dose of sumatriptan was estimated as the sum of AUClast and Clast/λz where Clast is the last observed concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUCinf was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).
Time Frame	Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter.

Arm/Group Title	Sumatriptan Alone	Erenumab + Sumatriptan
Arm/Group Description	All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	All participants who received erenumab plus sumatriptan (Group B, Part 2)
Measure Participants	30	20
Geometric Least Squares Mean (Standard Error) [hr*ng/mL]	144.32 (1.03)	144.81 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sumatriptan Alone, Erenumab + Sumatriptan
	Comments	The mean for each treatment was compared using a linear mixed effects model with group A (sumatriptan alone) as the reference treatment group. The linear mixed effects model included treatment (erenumab with sumatriptan vs sumatriptan alone) and period as a fixed effect and subject as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 90%; 0.96 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Sumatriptan
Description	Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed maximum observed plasma concentration (Cmax) was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).
Time Frame	Day 2 and day 5 at predose, 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter.

Arm/Group Title	Sumatriptan Alone	Erenumab + Sumatriptan
Arm/Group Description	All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	All participants who received erenumab plus sumatriptan (Group B, Part 2)
Measure Participants	30	20
Geometric Least Squares Mean (Standard Error) [ng/mL]	83.50 (1.05)	79.00 (1.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sumatriptan Alone, Erenumab + Sumatriptan
	Comments	The mean for each treatment was compared using a linear mixed effects model with group A (sumatriptan alone) as the reference treatment group. The linear mixed effects model included treatment (erenumab with sumatriptan vs sumatriptan alone) and period as a fixed effect and subject as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 90%; 0.82 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Participants Who Developed Anti-erenumab Antibodies
Description	Two validated assays were used to detect the presence of anti-erenumab antibodies. All samples were first tested in an electrochemiluminescence-based bridging assay to detect antibodies capable of binding to erenumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Binding/neutralizing antibody positive is defined as participants with an antibody positive postbaseline results and with a negative or no result at baseline.
Time Frame	Baseline and day 89

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) with a postbaseline antibody result.

Arm/Group Title	Group A: Placebo + Sumatriptan	Group B: Erenumab + Sumatriptan
Arm/Group Description	Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).
Measure Participants	10	20
Binding antibody positive	0 0%	1 4.5%
Neutralizing antibody positive	0 0%	1 4.5%

Adverse Events

Time Frame	From the first dose of study drug (sumatriptan, placebo or erenumab) until 84 days after the last dose (89 days). Part 1 includes AEs from day 1 to predose on day 4 and Part 2 includes AEs from day 4 through day 89.
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Part 1 Group A: Placebo + Sumatriptan		Part 1 Group B: Placebo + Sumatriptan		Part 2 Group A: Placebo + Sumatriptan		Part 2: Group B: Erenumab + Sumatriptan
Arm/Group Description	In Part 1 participants in Group A received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2.		In Part 1 participants in Group B received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2.		In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5.		In part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5.
All Cause Mortality
	Part 1 Group A: Placebo + Sumatriptan		Part 1 Group B: Placebo + Sumatriptan		Part 2 Group A: Placebo + Sumatriptan		Part 2: Group B: Erenumab + Sumatriptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part 1 Group A: Placebo + Sumatriptan		Part 1 Group B: Placebo + Sumatriptan		Part 2 Group A: Placebo + Sumatriptan		Part 2: Group B: Erenumab + Sumatriptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/22 (0%)		0/10 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Part 1 Group A: Placebo + Sumatriptan		Part 1 Group B: Placebo + Sumatriptan		Part 2 Group A: Placebo + Sumatriptan		Part 2: Group B: Erenumab + Sumatriptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		17/22 (77.3%)		9/10 (90%)		17/20 (85%)
Blood and lymphatic system disorders
Leukopenia	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Cardiac disorders
Palpitations	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Gastrointestinal disorders
Nausea	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
General disorders
Chest discomfort	0/12 (0%)		0/22 (0%)		1/10 (10%)		1/20 (5%)
Chest pain	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Discomfort	4/12 (33.3%)		0/22 (0%)		1/10 (10%)		0/20 (0%)
Fatigue	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Feeling hot	1/12 (8.3%)		1/22 (4.5%)		1/10 (10%)		1/20 (5%)
Injection site erythema	2/12 (16.7%)		4/22 (18.2%)		1/10 (10%)		2/20 (10%)
Injection site swelling	2/12 (16.7%)		4/22 (18.2%)		1/10 (10%)		2/20 (10%)
Injection site urticaria	1/12 (8.3%)		0/22 (0%)		0/10 (0%)		0/20 (0%)
Infections and infestations
Cystitis	1/12 (8.3%)		0/22 (0%)		0/10 (0%)		0/20 (0%)
Nasopharyngitis	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Viral infection	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Thermal burn	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Investigations
Blood potassium increased	0/12 (0%)		0/22 (0%)		1/10 (10%)		0/20 (0%)
Blood pressure systolic increased	1/12 (8.3%)		1/22 (4.5%)		0/10 (0%)		1/20 (5%)
Electrocardiogram PR prolongation	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Limb discomfort	1/12 (8.3%)		1/22 (4.5%)		0/10 (0%)		0/20 (0%)
Musculoskeletal chest pain	1/12 (8.3%)		0/22 (0%)		1/10 (10%)		0/20 (0%)
Musculoskeletal discomfort	0/12 (0%)		1/22 (4.5%)		0/10 (0%)		4/20 (20%)
Nervous system disorders
Burning sensation	0/12 (0%)		2/22 (9.1%)		0/10 (0%)		1/20 (5%)
Dizziness	0/12 (0%)		2/22 (9.1%)		0/10 (0%)		1/20 (5%)
Head discomfort	4/12 (33.3%)		8/22 (36.4%)		3/10 (30%)		8/20 (40%)
Headache	1/12 (8.3%)		3/22 (13.6%)		0/10 (0%)		4/20 (20%)
Paraesthesia	4/12 (33.3%)		3/22 (13.6%)		4/10 (40%)		4/20 (20%)
Renal and urinary disorders
Haematuria	1/12 (8.3%)		1/22 (4.5%)		1/10 (10%)		3/20 (15%)
Leukocyturia	1/12 (8.3%)		1/22 (4.5%)		0/10 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Pharyngeal paraesthesia	0/12 (0%)		1/22 (4.5%)		0/10 (0%)		1/20 (5%)
Throat irritation	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)
Throat tightness	2/12 (16.7%)		1/22 (4.5%)		2/10 (20%)		1/20 (5%)
Vascular disorders
Raynaud's phenomenon	0/12 (0%)		0/22 (0%)		0/10 (0%)		1/20 (5%)

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.