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

Phase 3

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Apadenoson	Apadenoson SPECT-MPI	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.
Adenosine	Apadenoson SPECT-MPI	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.
Apadenoson	Adenosine SPECT-MPI	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.
Adenosine	Adenosine SPECT-MPI	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Locations (122): Forest Investigative Site 152
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Birmingham, Alabama, United States
Forest Investigative Site 250
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Mobile, Alabama, United States
Forest Investigative Site 223
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Phoenix, Arizona, United States
Forest Investigative Site 191
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Phoenix, Arizona, United States
Forest Investigative Site 230
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Jonesboro, Arkansas, United States
Forest Investigative Site 153
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Little Rock, Arkansas, United States
Forest Investigative Site 108
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La Mesa, California, United States
Forest Investigative Site 111
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Mission Viejo, California, United States
Forest Investigative Site 234
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Murrieta, California, United States
Forest Investigative Site 146
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Roseville, California, United States
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Forest Investigative Site 152
🇺🇸Birmingham, Alabama, United States