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

Phase 3

Terminated

Conditions: Coronary Artery Disease

Interventions: Drug: Apadenoson SPECT-MPI
Drug: Adenosine SPECT-MPI

Registration Number: NCT00990327

Lead Sponsor: Forest Laboratories

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

Status: TERMINATED

Sex: All

Target Recruitment: 863

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

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

Trial Locations

Locations (122): Forest Investigative Site 235
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Akron, Ohio, United States
Forest Investigative Site 229
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Spartanburg, South Carolina, United States
Forest Investigative Site 227
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Chicago, Illinois, United States
Forest Investigative Site 106
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Miami, Florida, United States
Forest Investigative Site 113
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Indianapolis, Indiana, United States
Forest Investigative Site 183
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Miami, Florida, United States
Forest Investigative Site 133
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Overland Park, Kansas, United States
Forest Investigative Site 306
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Salvador, Bahia, Brazil
Forest Investigative Site 214
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Fargo, North Dakota, United States
Forest Investigative Site 116
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Honolulu, Hawaii, United States
Forest Investigative Site 177
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Saint Louis Park, Minnesota, 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 164
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Gainesville, Florida, United States
Forest Investigative Site 233
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Edgewater, Florida, United States
Forest Investigative Site 316
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Niteroi, Brazil
Forest Investigative Site 318
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Porto Alegre - RS, Brazil
Forest Investigative Site 319
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Rio de Janeiro - RJ, Brazil
Forest Investigative Site 315
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Rio de Janeiro, Brazil
Forest Investigative Site 132
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Hartford, Connecticut, United States
Forest Investigative Site 201
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Naples, Florida, United States
Forest Investigative Site 172
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Simpsonville, South Carolina, United States
Forest Investigative Site 126
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Jacksonville Beach, Florida, United States
Forest Investigative Site 180
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Melbourne, Florida, United States
Forest Investigative Site 313
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Curitiba, Brazil
Forest Investigative Site 301
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Salvador - BA, Brazil
Forest Investigative Site 190
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Bend, Oregon, United States
Forest Investigative Site 192
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Johnson City, Tennessee, United States
Forest Investigative Site 137
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Boise, Idaho, United States
Forest Investigative Site 311
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Campinas, Brazil
Forest Investigative Site 309
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Passo Fundo - RS, Brazil
Forest Investigative Site 304
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Rio de Janeiro - RJ, Brazil
Forest Investigative Site 193
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Baltimore, Maryland, United States
Forest Investigative Site 120
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Jacksonville, Florida, United States
Forest Investigative Site 198
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Jacksonville, Florida, United States
Forest Investigative Site 167
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Johnson City, Tennessee, United States
Forest Investigative Site 118
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Jacksonville, Florida, United States
Forest Investigative Site 124
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Jacksonville, Florida, United States
Forest Investigative Site 307
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Curitiba, Parana, Brazil
Forest Investigative Site 317
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Brasília - DF, Brazil
Forest Investigative Site 149
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Charleston, South Carolina, United States
Forest Investigative Site 231
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Tomball, Texas, United States
Forest Investigative Site 232
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Tomball, Texas, United States
Forest Investigative Site 250
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Mobile, Alabama, United States
Forest Investigative Site 173
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Winfield, Illinois, United States
Forest Investigative Site 109
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South Portland, Maine, United States
Forest investigative Site 197
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Westminster, Maryland, United States
Forest Investigative Site 171
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West Des Moines, Iowa, United States
Forest Investigative Site 107
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Scarborough, Maine, United States
Forest Investigative Site 159
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St. Louis, Missouri, United States
Forest Investigative Site 176
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Kansas City, Missouri, United States
Forest Investigative Site 207
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Petoskey, Michigan, United States
Forest Investigative Site 165
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Kingston, New York, United States
Forest Investigative Site 139
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Massapequa, New York, United States
Forest Investigative Site 208
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Raleigh, North Carolina, United States
Forest Investigative Site 249
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Sanford, North Carolina, United States
Forest Investigative Site163
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Columbus, Ohio, United States
Forest Investigative Site 161
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Columbus, Ohio, United States
Forest Investigative Site 101
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Westlake, Ohio, United States
Forest Investigative Site 213
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Camp Hill, Pennsylvania, United States
Forest Investigative Site 218
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Philadelphia, Pennsylvania, United States
Forest Investigative Site 160
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Pittsburgh, Pennsylvania, United States
Forest Investigative Site 252
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Grapevine, Texas, United States
Forest Investigative Site 308
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Belo Horizonte - MG, Brazil
Forest Investigative Site 200
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McKinney, Texas, United States
Forest Investigative Site 181
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Plano, Texas, United States
Forest Investigative Site 253
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San Antonio, Texas, United States
Forest Investigative Site 236
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Provo, Utah, United States
Forest Investigative Site 151
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Seattle, Washington, United States
Forest Investigative Site 142
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Spokane, Washington, United States
Forest Investigative Site 144
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Madison, Wisconsin, United States
Forest Investigative Site 314
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Curitiba - PR, Brazil
Forest Investigative Site 305
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Curitiba, Brazil
Forest Investigative Site 310
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Porto Alegre - RS, Brazil
Forest Investigative Site 303
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São José, Brazil
Forest Investigative Site 302
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São Paulo - SP, Brazil
Forest Investigative Site 312
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São Paulo - SP, Brazil
Forest Investigative Site 152
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Birmingham, 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 225
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Sacramento, California, United States
Forest Investigative Site 122
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Sacramento, California, United States
Forest Investigative Site 240
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Tampa, Florida, United States
Forest Investigative Site 143
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Detroit, Michigan, United States
Forest Investigative Site 182
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Oklahoma City, Oklahoma, United States
Forest Investigative Site 217
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Portland, Oregon, United States
Forest Investigative Site 138
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Boise, Idaho, United States
Forest Investigative Site 185
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Sandusky, Ohio, United States
Forest Investigative Site 212
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Buffalo, New York, United States
Forest Investigative Site 248
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Crestview Hills, Kentucky, United States
Forest Investigative Site 115
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Albany, New York, United States
Forest Investigative Site 186
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Sugar Land, Texas, United States
Forest Investigative Site 156
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Lorain, Ohio, United States
Forest Investigative Site 187
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Sellersville, Pennsylvania, United States
Forest Investigative Site 128
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Amarillo, Texas, United States
Forest Investigative Site 210
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Charlottesville, Virginia, United States
Forest Investigative Site 154
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Philadelphia, Pennsylvania, United States
Forest Investigative Site 117
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Wyomissing, Pennsylvania, 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 105
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Santa Rosa, California, United States
Forest Investigative Site 146
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Roseville, California, United States
Forest Investigative Site 196
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Walnut Creek, California, United States
Forest Investigative Site 102
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Newark, Delaware, United States
Forest Investigative Site 205
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Daytona Beach, Florida, United States
Forest Investigative Site 125
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Jacksonville, Florida, United States
Forest Investigative Site 155
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Augusta, Georgia, United States
Forest Investigative Site 238
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Wellington, Florida, United States
Forest Investigative Site 199
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Cumming, Georgia, United States
Forest Investigative Site 204
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Tucker, Georgia, United States
Forest Investigative Site 228
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Joliet, Illinois, United States
Forest Investigative Site 168
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Valparaiso, Indiana, United States
Forest Investigative Site 241
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Owensboro, Kentucky, United States
Forest Investigative Site 257
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Covington, Louisiana, United States
Forest Investigative Site 114
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Auburn, Maine, United States
Forest Investigative Site 202
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Alexandria, Louisiana, United States
Forest Investigative Site 131
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Tupelo, Mississippi, United States
Forest Investigative Site 224
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Manhasset, New York, United States
Forest Investigative Site 188
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Missoula, Montana, United States
Forest Investigative Site 134
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Philadelphia, Pennsylvania, United States
Forest Investigative Site 110
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Roanoke, Virginia, United States