Overview

This a Phase 3, prospective, open-label, multicenter study of [15-O]-H2O injection for PET imaging of subjects with suspected CAD. Approximately 182 evaluable participants with suspected CAD referred for testing will be included in the study at approximately 10 study sites in the United States and Europe. Approximately 215 participants will be enrolled to account for an estimated 15% drop-out rate. Screening assessments will occur prior to enrollment to confirm eligibility. All participants will receive two doses of [15-O]-H2O as part of a single PET imaging session (one dose at rest and one during pharmacological stress with adenosine). A safety follow-up phone call will occur 24 ± 8 hrs after completion of the [15-O]-H2O scan.

Eligibility

Inclusion Criteria:

1. Male and female participants ≥18 years;
2. Informed consent form (ICF) read, signed, and dated prior to any study procedures being performed;
3. Participants who fall into any one of the following categories:
   1. Have been referred for an ICA directly of after non-invasive testing (e.g., SPECT or PET MPI, stress echo, CCTA, ETT).
   2. Had an ICA with no intervention. However, if any stenosis >40% but ≤70% was observed, an FFR or iFR assessment was performed.
   3. Had a CCTA with normal coronaries or minimal CAD (no stenosis >25%).

             The SPECT study, PET 15O-H2O study, and ICA or CCTA testing need to be completed
             within a 30-day window, with time 0 defined as the date of the first of these three
             tests.
          4. 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 on the day of drug administration) must be
             negative; these participants must be practicing appropriate birth control from time of
             the screening visit until the 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.
          5. Male will need to use contraceptive methods until end of the follow-up period.
          6. Participants are able to comply with all study procedures as described in the
             protocol.
        Exclusion Criteria:
          1. Participants are unable to undergo (even partially) any of the imaging procedures;
          2. Participants with a known history of cardiac disease including:
               1. myocardial infarction, previous coronary revascularization, or chronic ischemic
                  cardiomyopathy
               2. primary myocardial disease such as cardiac amyloidosis or hypertrophic
                  cardiomyopathy
               3. known left ventricular dysfunction
               4. moderate or severe aortic or mitral stenosis or regurgitation
          3. Participants in whom adenosine stress testing is contraindicated, including but not
             limited to:
               1. Participants with severe COPD or chronic asthma.
               2. Participants with second- or third-degree atrioventricular block without a
                  pacemaker.
          4. Participants with claustrophobia to an extent that would limit their ability to
             undergo SPECT and PET imaging (patients whose claustrophobia is known to be readily
             controlled with drugs or psychological support may be enrolled).
          5. Participants who are on sildenafil (Viagra) or oral dipyridamole (Persantine,
             Aggrenox) therapy or on any PDE5 inhibitor (i.e. tadalafil, avanafil, vardenafil),and
             for whom its use cannot be terminated or suspended for ≥24 hours prior to treatment of
             study drug.
          6. Participants with significant co-morbidities that would prevent appropriate completion
             of the protocol procedures.
          7. Participants who have participated in another research study using investigational
             drugs within the 30 days prior to enrollment or through the duration of the trial
             (patients in observational studies with approved agents and participants known to be
             on placebo may be enrolled).
          8. Participants who have previously participated in this study.
          9. 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)