Clinical trial NCT00584818: Dose Finding Study of PB127 Ultrasound Contrast Agent in Healthy Volunteers and Patients With Coronary Artery Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Coronary Artery Disease
Keywords: coronary artery disease
chest pain
healthy volunteers
SPECT
angiogram
ultrasound
echocardiogram
perfusion
Lead sponsor: Point Biomedical
Sponsor class: INDUSTRY
First posted: 2008-01-02
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: To identify the minimum effective dose of PB127
timeFrame: 24 hours
measure: To identify the optimal stress infusion rate of PB127
timeFrame: 24 hours
Secondary outcomes:
measure: To assess the efficacy of PB127 MPE using the dose and stress infusion rate identified in Stages 1 and 2
timeFrame: 24 hours
measure: To evaluate the safety of PB127
timeFrame: 24 hours
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach VA Medical Center Cardiology Division
state: California
city: San Diego
country: United States
facility: University of California San Diego Division of Cardiology
state: California
city: Newark
country: United States
facility: Alfieri Cardiology
state: Delaware
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Overland Park
country: United States
facility: Midwest Cardiology Associates
state: Kansas
city: Shawnee Mission
country: United States
facility: The Center for Cardiovascular Studies Kramer and Crouse Cardiology
state: Kansas
city: Auburn
country: United States
facility: Androscoggin Cardiovascular Associates
state: Maine
city: Kansas City
country: United States
facility: Cardiovascular Consultants
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University Medical Center
state: Missouri
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cardiovascular Institute
state: Pennsylvania
city: Austin
country: United States
facility: Seton Healthcare Network Brackenridge Hospital
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Spokane
country: United States
facility: Inland Cardiology
state: Washington
city: Spokane
country: United States
facility: Northwest Cardiovascular Research Institute Spokane Cardiology
state: Washington
Study officials:
affiliation: POINT Biomedical Corp.
name: Alexander Ehlgen, MD, PhD
role: STUDY_DIRECTOR
References: