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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Healthy
• Intervention / Treatment: Drug: PB127 for Injectable Suspension

• Study Type: Interventional
• Enrollment (Actual): 205
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90822
      • Long Beach VA Medical Center Cardiology Division
    • San Diego, California, United States, 92103
      • University of California San Diego Division of Cardiology
  • Delaware
    • Newark, Delaware, United States, 19713
      • Alfieri Cardiology
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Midwest Cardiology Associates
    • Shawnee Mission, Kansas, United States, 66204
      • The Center for Cardiovascular Studies Kramer and Crouse Cardiology
  • Maine
    • Auburn, Maine, United States, 04210
      • Androscoggin Cardiovascular Associates
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Cardiovascular Consultants
    • St. Louis, Missouri, United States, 63110
      • St. Louis University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Cardiovascular Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Heart
    • Austin, Texas, United States, 78701
      • Seton Healthcare Network Brackenridge Hospital
  • Washington
    • Spokane, Washington, United States, 99204
      • Northwest Cardiovascular Research Institute Spokane Cardiology
    • Spokane, Washington, United States, 99204
      • Inland Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Stages 1 and 2

1. Men and women
2. Ages 18 30
3. Normal volunteers
4. No history (or suspicion) of CAD

Stage 3

1. Men and women with known or suspected CAD
2. Ages 18 years and older

3. Scheduled for or undergone clinically indicated coronary angiography within 28 days prior to or following Study Day 1

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

Exclusion Criteria:

1. Unable to provide written informed consent
2. Women who are pregnant or lactating

3. Known hypersensitivity or known contraindication to:

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

23. Liver disease, characterized by or including one or more of the following

    1. Elevated total bilirubin > upper limit of normal
    2. Currently elevated hepatic enzymes >3X upper limit of normal
24. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Point Biomedical
• Investigators: Study Director: Alexander Ehlgen, MD, PhD, POINT Biomedical Corp.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 20, 2007
• First Posted (Estimate): January 2, 2008

Study Record Updates

• Last Update Posted (Estimate): April 25, 2008
• Last Update Submitted That Met QC Criteria: April 23, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Keywords: chest pain; ultrasound; coronary artery disease; healthy volunteers; SPECT; perfusion; echocardiogram; angiogram
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 127-013