Dose Finding Study of PB127 Ultrasound Contrast Agent in Healthy Volunteers and Patients With Coronary Artery Disease

Inclusion criteria

Stages 1 and 2

• Men and women
• Ages 18 30
• Normal volunteers
• No history (or suspicion) of CAD

Stage 3

• Men and women with known or suspected CAD
• Ages 18 years and older
• Scheduled for or undergone clinically indicated coronary angiography within 28 days prior to or following Study Day 1

• Coronary angiography within 28 days prior to Study Day 1 and/or SPECT must have been non-interventional
• Coronary angiography images available in digital format (non cine) for transmission to core laboratory
• Scheduled for or undergone SPECT within 28 days prior to or following Study Day 1

Exclusion criteria

• Unable to provide written informed consent
• Women who are pregnant or lactating
• Known hypersensitivity or known contraindication to:

• Dipyridamole
• Ultrasound contrast agents (including PB127 and excipients)
• Blood, blood products, albumin, egg whites, or protein
• Use of caffeine or xanthine containing products within the 24 hours prior to PB127 administration on Study Day 1 (Stages 2 and 3)
• Previous exposure to PB127
• Inadequate echocardiographic windows
• Heart transplant
• Known right to left shunt, including atrial septal defect
• History of CABG
• Current uncontrolled ventricular tachycardia, atrial fibrillation, atrial tachycardia, or atrial flutter
• Pacemaker or defibrillator
• Unstable angina grade CCS Class IV severity with ongoing symptoms and/or ongoing infusion of IV nitroglycerin
• Second degree or greater heart block
• Hypertension (SPB >200 and/or DBP >110 mmHg on two consecutive readings within 1 hour prior to PB127 administration)
• Hypotension (SPB <90 mmHg on two consecutive readings within 1 hour prior to PB127 administration)
• Severe aortic stenosis (>100 mmHg peak transvalvar gradient or <0.6 cm2 estimated valve area)
• Pulmonary edema within the 7 days prior to Study Day 1
• Resting oxygen saturation of less than 90%
• Q wave MI or major surgery within the 7 days prior to Study Day 1
• PTCA within the 28 days prior to Study Day 1
• Chronic obstructive pulmonary disease or bronchospastic airway disease which, in the opinion of the Investigator, is significant enough to contraindicate dipyridamole
• Known history of severe pulmonary hypertension characterized by estimated pulmonary artery systolic pressure of >50 mmHg
• Liver disease, characterized by or including one or more of the following

• Elevated total bilirubin > upper limit of normal
• Currently elevated hepatic enzymes >3X upper limit of normal
• Medical conditions or other circumstances that would significantly decrease the chances of obtaining reliable data or achieving the study objectives (i.e., drug dependence, psychiatric disorder, dementia, or associated illness); extenuating circumstances or medical conditions that make it unlikely that a patient can complete the clinical trial or follow up evaluations; or other reasons for expected poor compliance with the clinical investigator's instructions