Treadmill Cardiovascular Safety Study of Erenumab (AMG 334) | NCT02575833

ID	Type	Description	Link
2015-002322-40	EudraCT Number

Treadmill Cardiovascular Safety Study of Erenumab (AMG 334) | NCT02575833 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received a single dose of placebo administered by intravenous infusion on day 1.	Drug: Placebo
Erenumab	Experimental	Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1.	Drug: Erenumab

Name	Type	Description	Arm Group Labels	Other Names
Erenumab	Drug	A single dose of erenumab 140 mg infused over approximately 60 minutes.	Erenumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Total Exercise Time	Total exercise time was assessed using an exercise treadmill test according to the standard Bruce protocol. The Bruce protocol is a standardized multistage treadmill test for assessing cardiovascular health, where the participant walks on an uphill treadmill in a graded exercise test with electrodes on the chest to monitor cardiac function. Every 3 minutes, the speed and incline of the treadmill are increased. There are 7 such stages for a total possible exercise time of 21 minutes.	Baseline and day 1, after dosing

Secondary Outcomes

Measure	Description	Time Frame
Time to Onset of Exercise-induced Angina	Time to onset of angina was defined as the time the participant received study drug to the time of event onset during the exercise treadmill test. If no event occurred the participant was censored at the exercise treadmill test stop time.	Day 1
Time to Onset of ≥ 1 mm ST-segment Depression

Contacts/Locations Module

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Jacksonville	Florida	32216	United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29878340	Background	Depre C, Antalik L, Starling A, Koren M, Eisele O, Lenz RA, Mikol DD. A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Erenumab on Exercise Time During a Treadmill Test in Patients With Stable Angina. Headache. 2018 May;58(5):715-723. doi: 10.1111/head.13316.

Label	URL
AmgenTrials clinical trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants randomized to receive a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
FG001	Erenumab

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 13, 2017	May 21, 2018

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants randomized to receive a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
BG001	Erenumab	Participants randomized to receive a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

- ParticipantsBG00044
- ParticipantsBG00145
- ParticipantsBG00289

Title	Measurements

Age, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00044 ParticipantsBG00145 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00044 ParticipantsBG00145 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00044 ParticipantsBG00145 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00044 ParticipantsBG00145 ParticipantsBG002

Baseline Total Exercise Time

Total exercise time (TET) was assessed using an exercise treadmill test according to the standard Bruce protocol.

The Bruce protocol is a standardized multistage treadmill test for assessing cardiovascular health, where the participant walks on an uphill treadmill in a graded exercise test with electrodes on the chest to monitor cardiac function. Every 3 minutes, the speed and incline of the treadmill are increased. There are 7 such stages for a total possible exercise time of 21 minutes.

Participants with non-missing values; baseline TET value was not calculated for two participants in the Erenumab arm due to disqualified screening values.

Mean

Standard Deviation

seconds

Title	Denominators	Categories
	ParticipantsBG00044 ParticipantsBG001

Stratification Factor: Total Exercise Time

Two participants in the Erenumab arm were incorrectly stratified to the < 7 minutes stratum due to disqualified screening TET values.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00044 ParticipantsBG00145 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Total Exercise Time

Total exercise time was assessed using an exercise treadmill test according to the standard Bruce protocol.

Participants who received study drug and completed the baseline and post-randomization exercise treadmill tests

Posted

Least Squares Mean

Standard Error

seconds

Baseline and day 1, after dosing

ID	Title	Description
OG000	Placebo	Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
OG001	Erenumab	Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.

Units	Counts
Participants	OG00044 OG00142

Title

Denominators

Categories

Title	Measurements
	OG0008.1± 14.4 OG001-2.9± 14.8

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The primary endpoint was analyzed using an analysis of variance model with terms for treatment group and randomization strata (< 7 or ≥ 7 minutes). If the lower bound of the 90% confidence interval (CI) of the difference in change from baseline in exercise duration was above the non-inferiority margin of -90 seconds, then the hypothesis that erenumab does not decrease exercise duration would be supported.					Treatment Difference	-11.0	Standard Error of the Mean	20.4	2-Sided	90	-44.9	22.9					Non-Inferiority	The non-inferiority margin was -90 seconds.

Secondary

Time to Onset of Exercise-induced Angina

Time to onset of angina was defined as the time the participant received study drug to the time of event onset during the exercise treadmill test. If no event occurred the participant was censored at the exercise treadmill test stop time.

Participants who received study drug and completed the post-randomization exercise treadmill test

Posted

Median

90% Confidence Interval

seconds

Day 1

ID	Title	Description
OG000	Placebo	Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
OG001	Erenumab	Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.

Units	Counts
Participants	OG000

Secondary

Time to Onset of ≥ 1 mm ST-segment Depression

Time to onset of ≥ 1 mm ST-segment depression was defined as the time the participant received study drug to the time of event onset during the exercise treadmill test. If no event occurred the participant was censored at the exercise treadmill test stop time.

Heart rate and rhythm were monitored during the exercise treadmill test by electrocardiography (ECG).

Participants who received study drug and completed the post-randomization exercise treadmill test.

Posted

Median

90% Confidence Interval

seconds

Day 1

ID	Title	Description
OG000	Placebo	Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
OG001	Erenumab	Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	0	44	1	44	6	44
EG001	Erenumab 140 mg	Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	0	44	0	44	4	44

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected44 at risk EG0010 affected44 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected44 at risk EG0010 affected44 at risk
Viral infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected44 at risk EG0010 affected44 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected44 at risk EG0012 affected44 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected44 at risk EG0012 affected44 at risk
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected44 at risk EG0010 affected44 at risk

Ancestor Terms

ID	Term
D017202	Myocardial Ischemia
D006331	Heart Diseases
D014652	Vascular Diseases
D002637	Chest Pain
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020
Asian	BG0000 BG0011 BG0021
Black (or African American)	BG0005 BG0011 BG0026
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020
White	BG00037 BG00143 BG00280
Multiple	BG0000 BG0010 BG0020
Other	BG0002 BG0010 BG0022

Group IDs	Statistical Method	Statistical Comment	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	Stratified Log Rank	Log rank test stratified by baseline total exercise time strata (< 7 minutes or ≥ 7 minutes).	0.69	Normal score	1.55					A normal score < 0 indicates fewer than expected events for erenumab 140 mg relative to placebo and therefore a longer survival time.	Superiority	The log-rank test statistic was used to compare the two treatment groups at a significance level of 0.10.
OG000 OG001	Cox Proportional Hazard	Adjusted by stratified baseline total exercise time strata (< 7 or ≥ 7 minutes)	0.69	Hazard Ratio (HR)	1.11	2-Sided	90	0.73	1.69	Hazard ratio estimates were obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicates a lower average event rate and a longer exercise-induced angina free survival for erenumab 140 mg relative to placebo.	Superiority
OG000 OG001	Cox Proportional Hazard	Adjusted by continuous baseline total exercise time	0.44	Hazard Ratio (HR)	0.81	2-Sided	90	0.52	1.26	Hazard ratio estimates were obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicates a lower average event rate and a longer exercise-induced angina free survival for erenumab 140 mg relative to placebo.	Superiority
OG000 OG001	Cox Proportional Hazard	Adjusted by baseline total exercise time strata (< 7 or ≥ 7 minutes), age group (< 65, ≥ 65), and sex.	0.47	Hazard Ratio (HR)	0.82	2-Sided	90	0.52	1.28	Hazard ratio estimates were obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicates a lower average event rate and a longer exercise-induced angina free survival for erenumab 140 mg relative to placebo.	Superiority

Group IDs	Statistical Method	Statistical Comment	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	Stratified Log Rank	Log rank test stratified by baseline total exercise time strata (< 7 minutes or ≥ 7 minutes).	0.59	Normal score	2.2					A normal score < 0 indicates fewer than expected events for erenumab 140 mg relative to placebo and therefore a longer survival time.	Superiority	The log-rank test statistic was used to compare the two treatment groups at a significance level of 0.10.
OG000 OG001	Cox Proportional Hazard	Adjusted by stratified baseline total exercise time strata (< 7 or ≥ 7 minutes)	0.59	Hazard Ratio (HR)	1.14	2-Sided	90	0.76	1.69	Hazard ratio estimates were obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicates a lower average event rate and a longer exercise-induced ST-segment depression free survival for erenumab 140 mg relative to placebo.	Superiority
OG000 OG001	Cox Proportional Hazard	Adjusted by continuous baseline total exercise time	0.75	Hazard Ratio (HR)	1.08	2-Sided	90	0.73	1.60	Hazard ratio estimates were obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicates a lower average event rate and a longer exercise-induced ST-segment depression free survival for erenumab 140 mg relative to placebo.	Superiority
OG000 OG001	Cox Proportional Hazard	Adjusted by baseline total exercise time strata (< 7 or ≥ 7 minutes), age group (< 65, ≥ 65), and sex.	0.39	Hazard Ratio (HR)	1.24	2-Sided	90	0.82	1.87	Hazard ratio estimates were obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicates a lower average event rate and a longer exercise-induced ST-segment depression free survival for erenumab 140 mg relative to placebo.	Superiority

ID	Term
D060050	Angina, Stable
D000787	Angina Pectoris
D002318	Cardiovascular Diseases