Dose Finding Study of PB127 Ultrasound Contrast Agent in Healthy Volunteers and Patients With Coronary Artery Disease
Primary Purpose
Healthy, Coronary Artery Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PB127 for Injectable Suspension
Sponsored by
About this trial
This is an interventional diagnostic trial for Healthy focused on measuring coronary artery disease, chest pain, healthy volunteers, SPECT, angiogram, ultrasound, echocardiogram, perfusion
Eligibility Criteria
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
Sites / Locations
- Long Beach VA Medical Center Cardiology Division
- University of California San Diego Division of Cardiology
- Alfieri Cardiology
- University of Chicago Medical Center
- Midwest Cardiology Associates
- The Center for Cardiovascular Studies Kramer and Crouse Cardiology
- Androscoggin Cardiovascular Associates
- Cardiovascular Consultants
- St. Louis University Medical Center
- The Cleveland Clinic Foundation
- Oregon Health Sciences University
- University of Pittsburgh Cardiovascular Institute
- Seton Healthcare Network Brackenridge Hospital
- Austin Heart
- Inland Cardiology
- Northwest Cardiovascular Research Institute Spokane Cardiology
Outcomes
Primary Outcome Measures
To identify the minimum effective dose of PB127
To identify the optimal stress infusion rate of PB127
Secondary Outcome Measures
To assess the efficacy of PB127 MPE using the dose and stress infusion rate identified in Stages 1 and 2
To evaluate the safety of PB127
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00584818
Brief Title
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
2. Study Status
Record Verification Date
April 2008
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Point Biomedical
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Coronary Artery Disease
Keywords
coronary artery disease, chest pain, healthy volunteers, SPECT, angiogram, ultrasound, echocardiogram, perfusion
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
205 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
PB127 for Injectable Suspension
Other Intervention Name(s)
CARDIOsphere®
Intervention Description
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.
Primary Outcome Measure Information:
Title
To identify the minimum effective dose of PB127
Time Frame
24 hours
Title
To identify the optimal stress infusion rate of PB127
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
To assess the efficacy of PB127 MPE using the dose and stress infusion rate identified in Stages 1 and 2
Time Frame
24 hours
Title
To evaluate the safety of PB127
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Ehlgen, MD, PhD
Organizational Affiliation
POINT Biomedical Corp.
Official's Role
Study Director
Facility Information:
Facility Name
Long Beach VA Medical Center Cardiology Division
City
Long Beach
State/Province
California
ZIP/Postal Code
90822
Country
United States
Facility Name
University of California San Diego Division of Cardiology
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Alfieri Cardiology
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Midwest Cardiology Associates
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66209
Country
United States
Facility Name
The Center for Cardiovascular Studies Kramer and Crouse Cardiology
City
Shawnee Mission
State/Province
Kansas
ZIP/Postal Code
66204
Country
United States
Facility Name
Androscoggin Cardiovascular Associates
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
Facility Name
Cardiovascular Consultants
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
St. Louis University Medical Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pittsburgh Cardiovascular Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Seton Healthcare Network Brackenridge Hospital
City
Austin
State/Province
Texas
ZIP/Postal Code
78701
Country
United States
Facility Name
Austin Heart
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Inland Cardiology
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Northwest Cardiovascular Research Institute Spokane Cardiology
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
12. IPD Sharing Statement
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Dose Finding Study of PB127 Ultrasound Contrast Agent in Healthy Volunteers and Patients With Coronary Artery Disease
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