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

Study Overview
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Brief Summary
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The purpose of this study is to determine the dose of PB127 for detection and/or exclusion of coronary artery disease when used with cardiac ultrasound. This study also evaluates the safety of PB127.

Official Title
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A Phase 2 Dose-Finding Clinical Trial of CARDIOsphere® (PB127) in Normal Volunteers and in Patients With Known or Suspected Coronary Artery Disease

Conditions
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Healthy, Coronary Artery Disease

Intervention / Treatment
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* Drug: PB127 for Injectable Suspension


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: PB127 for Injectable Suspension|Stages 1 & 2 0.009 - 0.204 mg/kg continuous IV during rest and stress conditions. Infusion rate of 50 - 125 mL/hr will be adjusted for image quality and diagnostic quality. Infusion limited to 60 minutes or less. Stage 3 - will utilize infusion rate and dose established in Stages 1 & 2. 0.062 mg/kg continuous IV infusion at 150 mL/hr during rest and 100 mL/hr during stress conditions.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify the minimum effective dose of PB127 |  | 24 hours | 
| To identify the optimal stress infusion rate of PB127 |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of PB127 MPE using the dose and stress infusion rate identified in Stages 1 and 2 |  | 24 hours | 
| To evaluate the safety of PB127 |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SPECT, coronary artery disease, chest pain, healthy volunteers, angiogram, ultrasound, echocardiogram, perfusion