Stable Angina
Conditions
Keywords
Angina, Stable Angina, Cardiovascular Disease, Exercise-induced Angina
Brief summary
A phase 2a, multicenter, randomized, double-blind, placebo-controlled study in adults with stable angina to evaluate the effect of erenumab (AMG 334) compared to placebo on exercise time during an exercise treadmill test.
Interventions
DRUGErenumab
A single dose of erenumab 140 mg infused over approximately 60 minutes.
DRUGPlacebo
A single dose of a matching volume of placebo infused over approximately 60 minutes.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* History of chronic stable angina or at least 3 months prior to screening, with at least 1 angina episode per month * Ischemic heart disease documented by myocardial infarction, coronary angiography or a revascularization procedure * Receiving stable doses of cardiac medication * Completes 2 exercise treadmill tests during screening meeting protocol requirements
Exclusion criteria
* Participating in another investigational study * Current or prior malignancy within 5 years of randomization * Known sensitivity to any components of the investigational product * Not able to complete all protocol required study visits * Having the following within 3 months prior to or during screening: Unstable angina or acute coronary syndrome, transient Ischemic attack (TIA) or stroke, revascularization procedure, or instability in ST-segment depression between screening exercise treadmill tests, as assessed by the core electrocardiograph (ECG) laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Exercise Time | Baseline and day 1, after dosing | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Exercise-induced Angina | Day 1 | 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. |
| Time to Onset of ≥ 1 mm ST-segment Depression | Day 1 | 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). |
Countries
Bulgaria, Czechia, Latvia, New Zealand, Poland, Romania, Slovakia, South Africa, Switzerland, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to receive a single dose of placebo administered by intravenous infusion on day 1 prior to starting an exercise treadmill test. | 44 |
| 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. | 45 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Erenumab | Total |
|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 9.6 | 61.8 years STANDARD_DEVIATION 10.1 | 62.6 years STANDARD_DEVIATION 9.9 |
| Age, Customized 18 - < 65 years | 21 Participants | 23 Participants | 44 Participants |
| Age, Customized 65 - 85 years | 23 Participants | 22 Participants | 45 Participants |
| Baseline Total Exercise Time | 474.8 seconds STANDARD_DEVIATION 149.5 | 490.7 seconds STANDARD_DEVIATION 149.7 | 482.7 seconds STANDARD_DEVIATION 148.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 44 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black (or African American) | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 37 Participants | 43 Participants | 80 Participants |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 33 Participants | 36 Participants | 69 Participants |
| Stratification Factor: Total Exercise Time < 7 minutes | 18 Participants | 18 Participants | 36 Participants |
| Stratification Factor: Total Exercise Time ≥ 7 minutes | 26 Participants | 27 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 6 / 44 | 4 / 44 |
| serious Total, serious adverse events | 1 / 44 | 0 / 44 |
Outcome results
Primary
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.
Time frame: Baseline and day 1, after dosing
Population: Participants who received study drug and completed the baseline and post-randomization exercise treadmill tests
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Exercise Time | 8.1 seconds | Standard Error 14.4 |
| Erenumab | Change From Baseline in Total Exercise Time | -2.9 seconds | Standard Error 14.8 |
Comparison: 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.90% CI: [-44.9, 22.9]
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).
Time frame: Day 1
Population: Participants who received study drug and completed the post-randomization exercise treadmill test.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Onset of ≥ 1 mm ST-segment Depression | 420.0 seconds |
| Erenumab | Time to Onset of ≥ 1 mm ST-segment Depression | 407.0 seconds |
p-value: 0.59Stratified Log Rank
p-value: 0.5990% CI: [0.76, 1.69]Cox Proportional Hazard
p-value: 0.7590% CI: [0.73, 1.6]Cox Proportional Hazard
p-value: 0.3990% CI: [0.82, 1.87]Cox Proportional Hazard
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.
Time frame: Day 1
Population: Participants who received study drug and completed the post-randomization exercise treadmill test
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Onset of Exercise-induced Angina | 508.0 seconds |
| Erenumab | Time to Onset of Exercise-induced Angina | 500.0 seconds |
p-value: 0.69Stratified Log Rank
p-value: 0.6990% CI: [0.73, 1.69]Cox Proportional Hazard
p-value: 0.4490% CI: [0.52, 1.26]Cox Proportional Hazard
p-value: 0.4790% CI: [0.52, 1.28]Cox Proportional Hazard