14 CLINICAL STUDIES

Agreement between Regadenoson injection and ADENOSCAN
The efficacy and safety of Regadenoson injection were determined relative to ADENOSCAN in two randomized, double-blind studies (Studies 1 and 2) in 2,015 patients with known or suspected coronary artery disease who were indicated for pharmacologic stress MPI. A total of 1,871 of these patients had images considered valid for the primary efficacy evaluation, including 1,294 (69%) men and 577 (31%) women with a median age of 66 years (range 26–93 years of age). Each patient received an initial stress scan using ADENOSCAN (6-minute infusion using a dose of 0.14 mg/kg/min, without exercise) with a radionuclide gated SPECT imaging protocol. After the initial scan, patients were randomized to either Regadenoson injection or ADENOSCAN, and received a second stress scan with the same radionuclide imaging protocol as that used for the initial scan. The median time between scans was 7 days (range of 1–104 days).

The most common cardiovascular histories included hypertension (81%), CABG, PTCA or stenting (51%), angina (63%), and history of myocardial infarction (41%) or arrhythmia (33%); other medical history included diabetes (32%) and COPD (5%). Patients with a recent history of serious uncontrolled ventricular arrhythmia, myocardial infarction, or unstable angina, a history of greater than first-degree AV block, or with symptomatic bradycardia, sick sinus syndrome, or a heart transplant were excluded. A number of patients took cardioactive medications on the day of the scan, including β-blockers (18%), calcium channel blockers (9%), and nitrates (6%). In the pooled study population, 68% of patients had 0–1 segments showing reversible defects on the initial scan, 24% had 2–4 segments, and 9% had ≥ 5 segments.

Comparison of the images obtained with Regadenoson injection to those obtained with ADENOSCAN was performed as follows. Using the 17-segment model, the number of segments showing a reversible perfusion defect was calculated for the initial ADENOSCAN study and for the randomized study obtained using Regadenoson injection or ADENOSCAN. The agreement rate for the image obtained with Regadenoson injection or ADENOSCAN relative to the initial ADENOSCAN image was calculated by determining how frequently the patients assigned to each initial ADENOSCAN category (0–1, 2–4, 5–17 reversible segments) were placed in the same category with the randomized scan. The agreement rates for Regadenoson injection and ADENOSCAN were calculated as the average of the agreement rates across the three categories determined by the initial scan. Studies 1 and 2 each demonstrated that Regadenoson injection is similar to ADENOSCAN in assessing the extent of reversible perfusion abnormalities (Table 7).

Table 7 Agreement Rates in Studies 1 and 2

Use of Regadenoson injection in Patients with Inadequate Exercise Stress

The efficacy and safety of Regadenoson injection administered 3 minutes (Group

1. or 1 hour (Group 2) following inadequate exercise stress were evaluated in an open-label randomized, multi-center, non-inferiority study. Adequate exercise was defined as ≥ 85% maximum predicted heart rate and ≥ 5 METS. SPECT MPI was performed 60-90 minutes after Regadenoson injection administration in each group (MPI 1). Patients returned 1-14 days later to undergo a second stress MPI with Regadenoson injection without exercise (MPI 2).

All patients were referred for evaluation of coronary artery disease. Of the 1,147 patients randomized, a total of 1,073 patients received Regadenoson injection and had interpretable SPECT scans at all visits; 538 in Group 1 and 535 in Group 2. The median age of the patients was 62 years (range 28 to 90 years) and included 633 (59%) men and 440 (41%) women.

Images from MPI 1 and MPI 2 for the two groups were compared for presence or absence of perfusion defects. The level of agreement between the MPI 1 and the MPI 2 reads in Group 1 was similar to the level of agreement between MPI 1 and MPI 2 reads in Group 2. However, two patients receiving Regadenoson injection 3 minutes following inadequate exercise experienced a serious cardiac adverse reaction. No serious cardiac adverse reactions occurred in patients receiving Regadenoson injection 1 hour following inadequate exercise stress [see Adverse Reactions (6.1), Clinical Pharmacology (12.2)].