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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00584818
• Other study ID #: 127-013
• Status: Completed
• Phase: Phase 2
• First received: December 20, 2007
• Last updated: April 23, 2008
• Start date: November 2006
• Est. completion date: March 2008

Study information

• Verified date: April 2008
• Source: Point Biomedical
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Healthy
• Myocardial Ischemia

Intervention

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.

Locations

Country	Name	City	State
United States	Androscoggin Cardiovascular Associates	Auburn	Maine
United States	Austin Heart	Austin	Texas
United States	Seton Healthcare Network Brackenridge Hospital	Austin	Texas
United States	University of Chicago Medical Center	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Cardiovascular Consultants	Kansas City	Missouri
United States	Long Beach VA Medical Center Cardiology Division	Long Beach	California
United States	Alfieri Cardiology	Newark	Delaware
United States	Midwest Cardiology Associates	Overland Park	Kansas
United States	University of Pittsburgh Cardiovascular Institute	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	University of California San Diego Division of Cardiology	San Diego	California
United States	The Center for Cardiovascular Studies Kramer and Crouse Cardiology	Shawnee Mission	Kansas
United States	Inland Cardiology	Spokane	Washington
United States	Northwest Cardiovascular Research Institute Spokane Cardiology	Spokane	Washington
United States	St. Louis University Medical Center	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Point Biomedical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To identify the minimum effective dose of PB127		24 hours	Yes
Primary	To identify the optimal stress infusion rate of PB127		24 hours	Yes
Secondary	To assess the efficacy of PB127 MPE using the dose and stress infusion rate identified in Stages 1 and 2		24 hours	No
Secondary	To evaluate the safety of PB127		24 hours	Yes