Trial Outcomes & Findings for Treadmill Cardiovascular Safety Study of Erenumab (AMG 334) (NCT NCT02575833)

Last Updated: 2018-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

89 participants

Primary outcome timeframe

Baseline and day 1, after dosing

Results posted on

2018-08-24

Participant Flow

This study was conducted at 35 centers across the United States, South Africa, New Zealand, and the European Union (EU). Participants were enrolled from November 2015 to January 2017.

Participants were randomized in a 1:1 ratio to receive either a single dose of erenumab 140 mg or placebo intravenously (IV) prior to starting an exercise treadmill test. Randomization was stratified by the total exercise time average (\< 7 minutes or ≥ 7 minutes) of the 2 qualifying exercise treadmill tests performed during screening.

Participant milestones

Participant milestones
Measure	Placebo Participants randomized to receive a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	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.
Overall Study STARTED	44	45
Overall Study Received Study Drug	44	44
Overall Study COMPLETED	43	44
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants randomized to receive a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	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.
Overall Study Withdrawal by Subject	0	1
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=44 Participants Participants randomized to receive a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	Erenumab n=45 Participants 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.	Total n=89 Participants Total of all reporting groups
Age, Continuous	63.5 years STANDARD_DEVIATION 9.6 • n=44 Participants	61.8 years STANDARD_DEVIATION 10.1 • n=45 Participants	62.6 years STANDARD_DEVIATION 9.9 • n=89 Participants
Age, Customized 18 - < 65 years	21 Participants n=44 Participants	23 Participants n=45 Participants	44 Participants n=89 Participants
Age, Customized 65 - 85 years	23 Participants n=44 Participants	22 Participants n=45 Participants	45 Participants n=89 Participants
Sex: Female, Male Female	11 Participants n=44 Participants	9 Participants n=45 Participants	20 Participants n=89 Participants
Sex: Female, Male Male	33 Participants n=44 Participants	36 Participants n=45 Participants	69 Participants n=89 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=44 Participants	1 Participants n=45 Participants	3 Participants n=89 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=44 Participants	44 Participants n=45 Participants	86 Participants n=89 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=44 Participants	0 Participants n=45 Participants	0 Participants n=89 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=44 Participants	0 Participants n=45 Participants	0 Participants n=89 Participants
Race/Ethnicity, Customized Asian	0 Participants n=44 Participants	1 Participants n=45 Participants	1 Participants n=89 Participants
Race/Ethnicity, Customized Black (or African American)	5 Participants n=44 Participants	1 Participants n=45 Participants	6 Participants n=89 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=44 Participants	0 Participants n=45 Participants	0 Participants n=89 Participants
Race/Ethnicity, Customized White	37 Participants n=44 Participants	43 Participants n=45 Participants	80 Participants n=89 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=44 Participants	0 Participants n=45 Participants	0 Participants n=89 Participants
Race/Ethnicity, Customized Other	2 Participants n=44 Participants	0 Participants n=45 Participants	2 Participants n=89 Participants
Baseline Total Exercise Time	474.8 seconds STANDARD_DEVIATION 149.5 • n=44 Participants • Participants with non-missing values; baseline TET value was not calculated for two participants in the Erenumab arm due to disqualified screening values.	490.7 seconds STANDARD_DEVIATION 149.7 • n=43 Participants • Participants with non-missing values; baseline TET value was not calculated for two participants in the Erenumab arm due to disqualified screening values.	482.7 seconds STANDARD_DEVIATION 148.9 • n=87 Participants • Participants with non-missing values; baseline TET value was not calculated for two participants in the Erenumab arm due to disqualified screening values.
Stratification Factor: Total Exercise Time < 7 minutes	18 Participants n=44 Participants • Two participants in the Erenumab arm were incorrectly stratified to the \< 7 minutes stratum due to disqualified screening TET values.	18 Participants n=45 Participants • Two participants in the Erenumab arm were incorrectly stratified to the \< 7 minutes stratum due to disqualified screening TET values.	36 Participants n=89 Participants • Two participants in the Erenumab arm were incorrectly stratified to the \< 7 minutes stratum due to disqualified screening TET values.
Stratification Factor: Total Exercise Time ≥ 7 minutes	26 Participants n=44 Participants • Two participants in the Erenumab arm were incorrectly stratified to the \< 7 minutes stratum due to disqualified screening TET values.	27 Participants n=45 Participants • Two participants in the Erenumab arm were incorrectly stratified to the \< 7 minutes stratum due to disqualified screening TET values.	53 Participants n=89 Participants • Two participants in the Erenumab arm were incorrectly stratified to the \< 7 minutes stratum due to disqualified screening TET values.

PRIMARY outcome

Timeframe: Baseline and day 1, after dosing

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

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	Erenumab n=42 Participants Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
Change From Baseline in Total Exercise Time	8.1 seconds Standard Error 14.4	-2.9 seconds Standard Error 14.8

SECONDARY outcome

Timeframe: Day 1

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	Erenumab n=44 Participants Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
Time to Onset of Exercise-induced Angina	508.0 seconds Interval 405.0 to 572.0	500.0 seconds Interval 420.0 to 540.0

SECONDARY outcome

Timeframe: Day 1

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

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).

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	Erenumab n=44 Participants Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
Time to Onset of ≥ 1 mm ST-segment Depression	420.0 seconds Interval 409.0 to 480.0	407.0 seconds Interval 380.0 to 443.0

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Erenumab 140 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=44 participants at risk Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	Erenumab 140 mg n=44 participants at risk Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
Cardiac disorders Atrial fibrillation	2.3% 1/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Other adverse events
Measure	Placebo n=44 participants at risk Participants received a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.	Erenumab 140 mg n=44 participants at risk Participants received a single dose of erenumab 140 mg administered by intravenous infusion on day 1 prior to starting an exercise treadmill test.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.5% 2/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	2.3% 1/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.5% 2/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	4.5% 2/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Influenza	4.5% 2/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Viral infection	4.5% 2/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/44 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER