Primary:* To demonstrate non-inferiority between the level of agreement in diagnosis (i.e. patient classification of normal, mild/moderate or severe ischemic disease based on the number of reversible perfusion segments) between sequential adenosine…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy endpoint:
-The level of agreement of diagnosis (i.e. patient classification of normal,
mild/moderate or severe ischemic disease based on the number of reversible
perfusion segments) between sequential adenosine SPECT-MPI versus the level of
agreement in diagnosis between an adenosine and an apadenoson SPECT-MPI.
Secondary outcome
Secondary efficacy variables:
- a.o. the 'summed stress score' (SSS), wall motion, extent of ischemia,
location of perfusion defects according to coronary artery territory and
calculation of sensitivity and specificity using angiography results compared
to diagnostic classification (ischemic versus non-ischemic based on the number
of reversible perfusion defects) resulting from SPECT-MPI.
Safety:
-comparison of the incidences and VAS Symptom-Intensity Measure for commonly
reported TEAEs as dyspnea, flushing, chest pain, headache, nausea, dizziness
and abdominal discomfort.
- incidence and severity of AEs, changes in clinical laboratory findings,
physical examinations, vital signs, ECGs, the number of discontinuations due to
AEs, incidence of second or third degree AV block, and subject-rated Overall
Bother Measure.
Background summary
Currently available pharmacological stress agent used in myocardial perfusion
is considered to be nonselective and can cause several adverse events.
Apadenoson is a new A2A agonist that exhibits greater binding selectivity for
the A2A receptor over other adenosine receptors: the A1, A2B, and A3 receptor
subtypes. Apadenoson has the potential to be as effective as adenosine for
SPECT-MPI and to have a lower incidence of undesirable side effects.
The objective of the study is to demonstrate non-inferiority between the level
of agreement in diagnosis (i.e. patient classification of normal, mild/moderate
or severe ischemic disease based on the number of reversible perfusion
segments) between sequential adenosine SPECT-MPI versus sequential SPECT-MPI
with adenosine and apadenoson.
Study objective
Primary:
* To demonstrate non-inferiority between the level of agreement in diagnosis
(i.e. patient classification of normal, mild/moderate or severe ischemic
disease based on the number of reversible perfusion segments) between
sequential adenosine SPECT-MPI versus sequential SPECT-MPI with adenosine and
apadenoson.
Secondary Gatekeeper Objective:
* Compare the safety and tolerability of pharmacologic stress with apadenoson
compared to adenosine based on incidence and severity of treatment-emergent
dyspnea, flushing, chest pain, headache, nausea, dizziness and abdominal
discomfort.
Other Secondary Objectives:
* Assess the safety and tolerability of apadenoson based on incidence and
severity of treatment emergent AEs (TEAEs), changes in clinical laboratory
findings, physical examinations, vital signs, ECGs, and the number of
discontinuations due to AEs.
* Compare incidence of second or third degree AV block associated with
apadenoson treatment to that seen following treatment with adenosine.
* Compare subject*s treatment experience with apadenoson to that of adenosine,
based on the subject-rated Overall Bother Measure.
* Evaluate comparability of pharmacologic stress imaging with apadenoson versus
adenosine based on additional endpoints of efficacy including summed stress
score (SSS), wall motion, extent of ischemia, location of perfusion defects
according to coronary artery territory and calculation of sensitivity and
specificity using angiography results compared to diagnostic classification
(ischemic versus non ischemic).
* Estimate PK parameters of apadenoson and ATL146a by sparse PK sampling
(select sites only).
Study design
A Phase 3, Randomized, Double-Blind Trial
Intervention
Subjects will receive two pharmacologic stress SPECT-MPI sessions: Period 1, a
clinically-indicated rest/stress gated SPECT-MPI with adenosine; followed by
Period 2, in which subjects will be randomized to a second rest/stress gated
SPECT-MPI with either adenosine or apadenoson (in a 1:1 assignment ratio).
Subjects will receive a single, bolus IV injection of apadenoson (50 µg/mL
sterile solution) in either a 2 mL (100 µg) or 3 mL (150 µg) final volume.
Subjects weighing less than 100 kg will receive 100 µg apadenoson, and subjects
weighing *100 kg will receive 150 µg apadenoson.
Study burden and risks
The most common side effects of Adenosine and Apadenoson include: chest pain
and discomfort, uncomfortable breathing, dizziness, headache, flushing
(blushing of the skin) and nausea. Adenosine and Apadenoson may cause a slight
increase in your heart rate and a decrease in your blood pressure, which could
cause dizziness or light-headedness.
Summary of procedures:
- 2x Clinical Labs and Serum Pregnancy test
- 2x Urine Pregnancy test
- 1x Height and Weight
- 2x Resting SPECT-MPI
- 2x Stress SPECT-MPI
- 2x Vital signs
- 2x ECG
- 1x Physical Examination
- 1x questionnaire
patients will be expected to:
* Not drink or eat caffeine-containing products (such as coffee, tea, sodas and
chocolate) or methylxanthine-containing foods for at least 24 hours before
SPECT-MPI tests
* Not receive a treatment of dipyridamole for at least 24 hours before
SPECT-MPI tests
* Not take certain medications, such as theophylline and
methylxanthine-containing medications for chronic obstructive pulmonary
disease, for at least 72 hours (3 days) before SPECT-MPI tests.
Forest Laboratories, Inc. 5 Science Park
CT 06511 New Haven
US
Forest Laboratories, Inc. 5 Science Park
CT 06511 New Haven
US
Listed location countries
Age
Inclusion criteria
* Referred for a clinically indicated rest /pharmacologic stress SPECT-MPI study
* Subjects must have either high pretest probability of CAD based on age and gender and chest pain symptomatology assessed using the ACC/AHA guidelines for relative risk
OR
Have previously demonstrated known coronary artery disease based on medical history of prior myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or diagnostic angiogram demonstrating 50% or greater stenosis in one or more vessel, as well as reporting chest pain indicative of angina or anginal equivalents within the month prior to Pre-Study Evaluation (based on ACC criteria, e.g. dyspnea or extreme fatigue).
* Can safely abstain from caffeine or methylxanthine containing foods for 24 hours, from dipyridamole for 24 hours, and from theophylline and methylxanthine containing medications for at least 72 hours (or 4 half-lives, whichever is longer)
* Cardiovascular medication routine must remain stable from the time of signed informed consent through the Period 2 SPECT-MPI
Exclusion criteria
* Treatment with dipyridamole within 24 hours, or theophylline, aminophylline, or pentoxifylline within 72 hours (or 4 half-lives, whichever is longer) prior to receiving apadenoson or adenosine
* Acute MI, new onset of ischemia or PCI within 30 days prior to SPECT-MPI at either Period 1 or Period 2; or CABG within 90 days prior to SPECT-MPI at either Period 1 or Period 2
* Active severe asthma or severe chronic obstructive pulmonary disease (COPD) which, in the Investigator*s opinion, places the subject at risk for severe bronchoconstriction
* History or evidence of clinically significant high grade AV block (including type 2 second or third degree block) or sinus node disease, such as sick sinus syndrome or symptomatic bradycardia, in the absence of a functioning permanently implanted pacemaker
* Evidence of hemodynamically significant valvular disease or outflow tract obstruction
* Uncontrolled severe hypertension or malignant ventricular arrhythmias
* Pretreatment hypotension (systolic BP < 90 mm Hg) or tachycardia (HR > 100 bpm)
* Known history of cerebral vascular accident or suspected transient ischemic attack within 30 days prior to signed informed consent
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-001245-32-NL |
| ClinicalTrials.gov | NCT01313572 |
| CCMO | NL37108.098.11 |