MYOVIEW Kit, Powder for solution for injection Ref.[10234] Active ingredients: Technetium ⁹⁹ᵐTc tetrofosmin

The relationship between Tc99m tetrofosmin plasma concentrations and successful imaging has not been explored in clinical trials.

Uptake in the myocardium is dependent on coronary flow and reaches a maximum of 1.2% of the injected dose (i.d.) at 5 minutes and 1% of the i.d. at 2 hours, respectively. Background activities in the blood, liver and lung were less than 5% of the administered activity in whole blood at 10 minutes post-injection, less than 4.5% i.d., after 60 minutes, and less than 2% i.d. after 30 minutes.

Elimination

Approximately 66% of the injected activity is excreted within 48 hours post-injection, with approximately 40% excreted in the urine and 26% in the feces.

Studies have not been conducted to evaluate carcinogenic potential or effects on fertility. Tetrofosmin sulphosalicylate was not mutagenic in vitro in the Ames test, mouse lymphoma, or human lymphocyte tests, nor was it clastogenic in vivo in the mouse micronucleus test.

14.1 Exercise/Resting Myocardial Perfusion Imaging Studies

A total of 252 subjects with ischemic heart disease or atypical chest pain were studied in two open-label, multi-center, clinical studies (study a and study b). Of these 252 subjects there were 212 (84%) males and 40 (16%) females with a mean age of 60.5 years (range 33.7 to 82.4 years).

All subjects had exercise and rest planar imaging with MYOVIEW and thallium-201; 191 (76%) subjects also had single photon emission computed tomography (SPECT) imaging. At peak exercise, maximum heart rate achieved and peak systolic blood pressure were comparable after MYOVIEW and thallium-201 exercise studies. The MYOVIEW and thallium-201 images were separated by a mean of 5.1 days (1-14 days before or 2-14 days after MYOVIEW). For MYOVIEW imaging, each subject received 185-296 MBq (5-8 mCi) Tc99m tetrofosmin at peak exercise and 555-888 MBq (15-24 mCi) Tc99m tetrofosmin at rest approximately 4 hours later. For thallium-201 imaging, subjects received thallium-201 55.5-74 MBq (1.5-2 mCi) at peak exercise.

The images were evaluated for the quality of the image (excellent, good or poor) and the diagnosis (with scores of 0 = normal, 1 = ischemia, 2 = infarct, 3 = mixed infarct and ischemia). The primary outcome variable was the percentage of correct diagnoses in comparison to the final clinical diagnosis. All planar images were blindly read; SPECT images were evaluated by the unblinded investigator. The results for each blinded reader are noted in Table 5.

Table 5. Overall Diagnostic Outcome:

14.2 Pharmacological Stress Myocardial Perfusion Imaging Studies

MYOVIEW imaging after pharmacologic stress was evaluated in two studies in subjects with known or suspected coronary artery disease (CAD). Three blinded reads were obtained for 57 subjects (45 male [79%], 12 female [21%]; mean age 60.1 years) all of whom had angiography. Subject level analyses were based on the finding of SPECT myocardial perfusion abnormalities in patients with angiographically confirmed disease. Subject level sensitivities for MYOVIEW ranged from 68-83% and subject level specificities ranged from 45-82% across readers and studies.

14.3 Ventricular Function Stress Myocardial Perfusion Imaging Studies

Two open-label, multicenter, identically designed, blinded image read studies were conducted to assess left ventricular function using MYOVIEW ECG gated SPECT (GSPECT) myocardial perfusion imaging. A total of 329 subjects (216 male [65.7%], 113 female [34.3%]); mean age of 60.4 years) with known or suspected heart disease or requiring ventricular function assessments were dosed with MYOVIEW. Of these, 297 were considered evaluable. MYOVIEW was administered at rest and at peak stress using either a one-day or a 2-day dosing protocol.

For both studies, all subjects' stress GSPECT exams were compared to the reference exam of radionuclide ventriculography with Tc99m labeled RBCs (multiple gated acquisition [MUGA]), performed 1 to 5 days after the second MYOVIEW injection. All subjects' GSPECT exams were assessed by 3 independent blinded readers per study. The MUGA exams were evaluated by an independent consensus panel composed of 3 blinded readers. Subject level assessments were based upon discrimination between normal and abnormal values for LVEF (LVEF ≥50% was considered normal) and normal and abnormal wall motion as judged visually. Sensitivity and specificity of LVEF determinations ranged from 81%-88% and 76%-85% respectively across studies and readers. Sensitivity and specificity of wall motion determinations ranged from 80%-92% and 68%-86% respectively across studies and readers.