A Phase 3, Multicenter, Open Label Study to Confirm the Diagnostic Potential of Intravenously Administered 15O- H2O to Identify Coronary Artery Disease During Pharmacological Stress and Resting Conditions Using PET Imaging

Prior treatment

• Subjects with a known history of cardiac disease including: a. myocardial infarction, previous coronary revascularization, or chronic ischemic cardiomyopathy b. primary myocardial disease such as cardiac amyloidosis or hypertrophic cardiomyopathy c. known left ventricular dysfunction d. moderate or severe aortic or mitral stenosis or regurgitation
• Subjects with claustrophobia to an extent that would limit their ability to undergo PET imaging (subjects whose claustrophobia is known to be readily controlled with drugs or psychological support may be enrolled).
• Subjects who are on sildenafil (Viagra), oral dipyridamole (Persantine, Aggrenox) therapy or subjects on any PDE5 inhibitor (i.e. tadalafil, avanafil, vardenafil), and for whom its use cannot be terminated or suspended for at least 5 half-lives prior to treatment of study drug..
• Subjects who have participated in another research study using investigational drugs within the 30 days prior to enrollment or through the duration of the trial (subjects in observational studies with approved agents and subjects known to be on placebo may be enrolled).
• Subjects who have previously participated in this study.

Other illness

• Subjects scheduled for, or planning to undergo, any interventional cardiac procedures between enrollment and ICA (pathway 1) or signing of informed consent and 15O-H2O PET MPI (pathway 2 and 3)

Other

• Subjects are unable to undergo (even partially) any of the imaging procedures;
• Subjects in whom adenosine stress testing is contraindicated, including but not limited to: a. Subjects with severe COPD or chronic asthma. b. Subjects with second- or third-degree atrioventricular block without a pacemaker.
• Subjects with significant co-morbidities that would prevent appropriate completion of the protocol procedures.

• Male and female subjects ≥18 years;
• Informed consent form (ICF) read, signed, and dated prior to any study procedures being performed;
• Subjects who fall into any one of the following categories: a. Have been referred for an ICA directly or after non-invasive testing (e.g., SPECT or PET MPI, stress echo, CCTA, ETT). b. Had an ICA with no intervention. However, if any stenosis ≥40% but ≤70% was observed, an FFR or iFR assessment must have been performed. c. Had a CCTA with normal coronaries or minimal CAD (< 25% stenosis).
• Women of Child Bearing Potential (WOCBP) must be non-pregnant, and non-lactating. For women of childbearing potential, the results of a urine human chorionic gonadotropin (HCG) pregnancy test (with the result known prior to drug administration) must be negative; these subjects must be practicing appropriate birth control from time of the screening until end of the follow-up period. For women who are either surgically sterile (have a documented bilateral tubal ligation or oophorectomy and/or hysterectomy) or are post-menopausal (cessation of menses for more than 1 year), enrollment in the study without a pregnancy test at screening is allowed.
• Male study subjects must use contraceptive methods until end of the follow-up period.
• Subjects are able to comply with all study procedures as described in the protocol.