Study of the Safety and Efficacy of Apadenoson for Detection of Myocardial Perfusion Defects Using SPECT MPI

Study Overview
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Brief Summary
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The purpose of this study is to see whether apadenoson is as effective as adenosine when used as a pharmacological stress agent in myocardial SPECT-Imaging to detect defects in the supply of blood to the heart muscle (myocardial perfusion defects). The study will also look at whether apadenoson is better tolerated than adenosine when used in SPECT-MPI.

Detailed Description
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Adenosine is an effective vasodilator used in SPECT-Myocardial Perfusion Imaging (SPECT-MPI). However, it produces transient symptoms that are poorly tolerated by most subjects. PGxHealth has designed a multi-center, randomized crossover, double-blind study to compare the safety and effectiveness of apadenoson to adenosine (Adenoscan®) in SPECT-MPI. Subjects who are clinical candidates for SPECT-MPI will be enrolled to undergo two sequential SPECT-MPI studies. The first study will use adenosine as the stress agent in approximately 1300 subjects. Eligible subjects will then be randomized in a 1:2 assignment ratio to receive a second SPECT-MPI using either adenosine or apadenoson as the pharmacologic stress agent, with the goal of obtaining a total of 753 subjects who complete both studies. The similarity of the results from the two adenosine:adenosine stress tests will be compared to those from the adenosine:apadenoson tests to assess efficacy. The incidence and intensity of commonly reported side effects will be compared to evaluate improved tolerability.

Official Title
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The ASPECT Trial: A Phase III, Randomized, Double-Blind Crossover Trial of Apadenoson for the Detection of Myocardial Perfusion Defects Using Single-Photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging (MPI)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Apadenoson SPECT-MPI
* Drug: Adenosine SPECT-MPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High pretest probability of CAD based on the ACC/AHA guidelines for relative risk, or past medical h/o CAD Exclusion Criteria: Ingestion of a caffeinated or methylxanthine food substance (e.g. chocolate, cocoa) within 24 hours before receiving apadenoson or adenosine 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 cardiac condition and rhythm disorder, in the absence of a functioning permanently implanted pacemaker Hemodynamically significant valvular disease, outflow tract obstruction, or uncontrolled severe hypertension Current significant medical, surgical, psychiatric, or other illness or pathology that could potentiate any adverse pharmacological event associated with an investigational drug Subject with past medical history of hepatitis B or C, or recent hepatitis A 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apadenoson<br>In period 1, subjects will receive a clinically-indicated rest/stress gated SPECT-MPI with adenosine. In period 2, subjects will receive a rest/stress gated SPECT-MPI with apadenoson or the active comparator: adenosine. | Drug: Apadenoson SPECT-MPI<br>* Apadenoson single bolus IV injection 100 or 150 ug<br>* Other names: DPC-A78445-00, DPH-068645-01, ATL146e, DWH 146e;Drug: Adenosine SPECT-MPI<br>* Single IV infusion for 6 minutes at a rate of 140 µg/kg body weight per minute.<br>* Other names: Adenoscan;|
| Active Comparator: Adenosine<br>In period 1, subjects will receive a clinically-indicated rest/stress gated SPECT-MPI with adenosine. In period 2, subjects will receive a rest/stress gated SPECT-MPI with apadenoson or the active comparator: adenosine. | Drug: Apadenoson SPECT-MPI<br>* Apadenoson single bolus IV injection 100 or 150 ug<br>* Other names: DPC-A78445-00, DPH-068645-01, ATL146e, DWH 146e;Drug: Adenosine SPECT-MPI<br>* Single IV infusion for 6 minutes at a rate of 140 µg/kg body weight per minute.<br>* Other names: Adenoscan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of myocardial perfusion defect as based on SPECT-MPI |  | Up to 2 hours after study drug administration in Period 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and patient rated intensity of most commonly reported side effects (e.g. dyspnea, flushing, chest pain, headache) associated with use of adenosine compared to apadenoson in SPECT-MPI |  | 1 hour after Period 2 study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery disease, Myocardial Perfusion Imaging