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Development of 1-Day Rest/Stress Cardiac PET Perfusion Imaging Protocol of BMS747158

Primary Purpose

Ischemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
BMS747158
Sponsored by
Lantheus Medical Imaging
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Ischemia focused on measuring Myocardial Perfusion, PET imaging, SPECT imaging, Coronary artery disease, Subjects that are male and nonpregnant female patients, presenting with reversible ischemia as characterized by a, rest/stress SPECT imaging study using, Technetium(99mTc)-labeled tracers

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provide signed IC prior to undergoing any study procedures
  • Be male or nonpregnant female, between the ages of 18 to 75 years, inclusive
  • Have:A rest/stress SPECT imaging study (either exercise or pharmacologic stress) within 21 days of enrollment, using 99mTc-labeled tracers and showing reversible ischemia

  • Female patients must:

    • be nonlactating,
    • no longer have child-bearing potential, either because they are post-menopausal (defined as amenorrhea ≥ 12 consecutive months, or because they have undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy)

Exclusion Criteria:

  • Presence of any condition that may disrupt and/or increase permeability of the BBB, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, acute central nervous system (CNS) infection, CNS tumor, autoimmune disease affecting the CNS, or CNS inflammatory
  • Current significant illness, pathology or physical examination or vital signs measurement-findings that could potentiate any adverse pharmacological event associated with a vasodilatory drug or any pathology that, in the opinion of the investigator, might confound the interpretation of the results of the study
  • Known hypersensitivity to adenosine, dipyridamole or aminophylline
  • Presence of any contraindications to exercise stress testing
  • History of New York Heart Association Class III or IV Congestive Heart Failure (CHF)
  • Any major surgery within 4 weeks prior to enrollment or planned within 2 weeks following completion of the 2-week telephone follow-up assessment
  • Inability to tolerate IV medication.
  • History of drug or alcohol abuse within the last year
  • Participation in any investigational drug, device, or placebo study within 6 months prior to study enrollment

Sites / Locations

  • Silicon Valley Medical Imaging
  • Scripps Memorial Hospital
  • Cedars-Sinai Medical Center
  • UCLA Medical Plaza
  • Radiological Associates of Sacramento
  • VA Healthcare System San Diego
  • Hartford Hospital
  • Yale University
  • Emory University Hospital
  • Primary Care Cardiology Research, Inc
  • Massachusetts General Hospital
  • Brigham & Women's Hospital
  • University of Michigan
  • Cardiovascular Consultants
  • Saint Louis University
  • Washington University School of Medicine
  • University of Medicine and Dentistry of New Jersey
  • Holy Name Hospital
  • Columbia University Medical Center
  • St. Francis Hospital
  • University Hospital Case Medical Center
  • Midwest Cardiology Research Foundation
  • Mountain States Health Alliance
  • East Tennessee Clinical Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1: dose range and dose interval

Cohort 2: Pharm&exercise stress Efficacy

Arm Description

Patients to receive either 2 or 3 IV bolus injections of BMS747158: 1 at rest and 1 or 2 during pharmacological or exercise stress, over a 1-day or 2-day period.

Patients to receive 2 IV bolus injections of BMS747158:1 at rest and 1 at stress For the Pharmacologic (Adenosine) Stress: Doses at rest to range between 2.9 and 3.4 mCi. Doses under stress to be a factor of 2.0 to 2.4 greater than the rest dose, resulting in a range of stress doses between 5.8 and 8.2 mCi. For the Exercise Stress: Doses at rest were to range between 1.7 and 2.0 mCi. Doses under stress were to be a factor of 3.0 to 3.6 greater than the rest dose, resulting in a range between 5.1 and 7.2 mCi.

Outcomes

Primary Outcome Measures

Cohort 1: Determination of Rest Dose: Dose Acquistion Time Product
The rest flurpiridaz dose to be used for subsequent efficacy studies was determined by a modeling method that simulated a range of injected doses using a single fixed injected dose at rest in each subject and a range of acquisition durations. From this, a dose acquisition time product (DATP was determined for each subject that specified the minimal dose for a given acquisition duration that yielded an image in that subject that was negligibly affected by photon counting statistics. Descriptive statistics were used to identify an appropriate rest dose for the population. No other statistical tests were performed
Cohort 2: Diagnostic Efficacy of One-day Rest/Stress BMS747158 PET MPI Sensitivity (SN) vs SPECT MPI Sensitivity
Diagnostic efficacy of one-day rest/stress BMS747158 PET MPI is measured by sensitivity as compared to single photon emission computed tomography (SPECT)MPI in the detection of coronary artery disease (CAD)using angiography or three-month cardiac events as the truth standard.
Cohort 1: Determination of Ratio of Stress Dose to Rest Dose
The stress flurpiridaz dose for subsequent same-day rest-stress efficacy studies was determined as a multiple of the rest dose by computer modeling. Images derived only from rest flurpiridaz administration were blended using image analysis with images derived only from administration of flurpiridaz following exercise or adenosine stress. The blending fraction that resulted in negligible change in reader interpretation of defect severity was determined for each subject. The minimum value that met this criterion for all subjects was used to calculate the ratio of the stress dose to the rest dose as a function of the delay between administration of the two doses for both adenosine stress and exercise stress separately. No statistical analysis was performed.
Cohort 2: Diagnostic Efficacy of One-day Rest/Stress BMS747158 PET MPI Specificity (SP) vs SPECT MPI Specificity
Diagnostic efficacy of one-day rest/stress BMS747158 PET MPI is measured by specificity as compared to single photon emission computed tomography (SPECT)MPI in the detection of coronary artery disease (CAD)using angiography or three-month cardiac events as the truth standard.

Secondary Outcome Measures

Full Information

First Posted
January 5, 2009
Last Updated
October 12, 2015
Sponsor
Lantheus Medical Imaging
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1. Study Identification

Unique Protocol Identification Number
NCT00849108
Brief Title
Development of 1-Day Rest/Stress Cardiac PET Perfusion Imaging Protocol of BMS747158
Official Title
A Phase 2, Open-Label, Randomized Multicenter Study for the Development of One-Day Rest/Stress Cardiac Positron Emission Tomography (PET) Perfusion Imaging Protocols of BMS747158
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lantheus Medical Imaging

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of this study is to get more information on using BMS747158 (the study drug),a drug with small amounts of radioactivity to allow for heart imaging, during a PET scan which can then be compared to other images such as SPECT. The safety and quality of images will be studied.
Detailed Description
The primary objectives of this study are: To acquire data for the development of one-day rest/stress cardiac PET perfusion imaging protocols for BMS747158 with comparable diagnostic image quality to a two-day rest/stress PET protocol To assess the safety of multiple doses of BMS747158 The secondary objectives of this study are: To assess PET imaging parameters and image quality following administration of BMS747158 at rest and at stress (pharmacologic or exercise) same day (at different time intervals) and 16-48 hours after the rest injection To assess feasibility of gated cardiac PET imaging with BMS747158 for left ventricular function assessment To assess agreement of one and two day rest/stress PET imaging with BMS747158 in patients with reversible ischemia with rest/stress single photon emission computed tomography (SPECT) imaging To perform a preliminary assessment of the diagnostic accuracy of one-day and two-day rest/stress PET perfusion imaging with BMS747158 as compared with invasive coronary angiography or computed tomography angiography (CTA) for detection of

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemia
Keywords
Myocardial Perfusion, PET imaging, SPECT imaging, Coronary artery disease, Subjects that are male and nonpregnant female patients, presenting with reversible ischemia as characterized by a, rest/stress SPECT imaging study using, Technetium(99mTc)-labeled tracers

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
176 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: dose range and dose interval
Arm Type
Experimental
Arm Description
Patients to receive either 2 or 3 IV bolus injections of BMS747158: 1 at rest and 1 or 2 during pharmacological or exercise stress, over a 1-day or 2-day period.
Arm Title
Cohort 2: Pharm&exercise stress Efficacy
Arm Type
Experimental
Arm Description
Patients to receive 2 IV bolus injections of BMS747158:1 at rest and 1 at stress For the Pharmacologic (Adenosine) Stress: Doses at rest to range between 2.9 and 3.4 mCi. Doses under stress to be a factor of 2.0 to 2.4 greater than the rest dose, resulting in a range of stress doses between 5.8 and 8.2 mCi. For the Exercise Stress: Doses at rest were to range between 1.7 and 2.0 mCi. Doses under stress were to be a factor of 3.0 to 3.6 greater than the rest dose, resulting in a range between 5.1 and 7.2 mCi.
Intervention Type
Drug
Intervention Name(s)
BMS747158
Other Intervention Name(s)
There are no other names
Intervention Description
dosages at rest and at stress were not to exceed a total of 14 mCi. Cohort 1: Patients received either 2 or 3 IV bolus injections of BMS747158: 1 at rest and 1 or 2 during stress, over a 1-day or 2-day period. Cohort 2: Patients to recieve IV bolus injections of BMS747158: For the Pharmacologic (Adenosine) Stress: Doses at rest were to range between 2.9 and 3.4 mCi. Doses under stress were to be a factor of 2.0 to 2.4 greater than the rest dose, resulting in a range of stress doses between 5.8 and 8.2 mCi. For the Exercise Stress: Doses at rest were to range between 1.7 and 2.0 mCi. Doses under stress were to be a factor of 3.0 to 3.6 greater than the rest dose, resulting in a range between 5.1 and 7.2 mCi.
Primary Outcome Measure Information:
Title
Cohort 1: Determination of Rest Dose: Dose Acquistion Time Product
Description
The rest flurpiridaz dose to be used for subsequent efficacy studies was determined by a modeling method that simulated a range of injected doses using a single fixed injected dose at rest in each subject and a range of acquisition durations. From this, a dose acquisition time product (DATP was determined for each subject that specified the minimal dose for a given acquisition duration that yielded an image in that subject that was negligibly affected by photon counting statistics. Descriptive statistics were used to identify an appropriate rest dose for the population. No other statistical tests were performed
Time Frame
Dosing visit
Title
Cohort 2: Diagnostic Efficacy of One-day Rest/Stress BMS747158 PET MPI Sensitivity (SN) vs SPECT MPI Sensitivity
Description
Diagnostic efficacy of one-day rest/stress BMS747158 PET MPI is measured by sensitivity as compared to single photon emission computed tomography (SPECT)MPI in the detection of coronary artery disease (CAD)using angiography or three-month cardiac events as the truth standard.
Time Frame
Dosing visit
Title
Cohort 1: Determination of Ratio of Stress Dose to Rest Dose
Description
The stress flurpiridaz dose for subsequent same-day rest-stress efficacy studies was determined as a multiple of the rest dose by computer modeling. Images derived only from rest flurpiridaz administration were blended using image analysis with images derived only from administration of flurpiridaz following exercise or adenosine stress. The blending fraction that resulted in negligible change in reader interpretation of defect severity was determined for each subject. The minimum value that met this criterion for all subjects was used to calculate the ratio of the stress dose to the rest dose as a function of the delay between administration of the two doses for both adenosine stress and exercise stress separately. No statistical analysis was performed.
Time Frame
Dosing visit
Title
Cohort 2: Diagnostic Efficacy of One-day Rest/Stress BMS747158 PET MPI Specificity (SP) vs SPECT MPI Specificity
Description
Diagnostic efficacy of one-day rest/stress BMS747158 PET MPI is measured by specificity as compared to single photon emission computed tomography (SPECT)MPI in the detection of coronary artery disease (CAD)using angiography or three-month cardiac events as the truth standard.
Time Frame
Dosing Visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provide signed IC prior to undergoing any study procedures Be male or nonpregnant female, between the ages of 18 to 75 years, inclusive Have:A rest/stress SPECT imaging study (either exercise or pharmacologic stress) within 21 days of enrollment, using 99mTc-labeled tracers and showing reversible ischemia Female patients must: be nonlactating, no longer have child-bearing potential, either because they are post-menopausal (defined as amenorrhea ≥ 12 consecutive months, or because they have undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) Exclusion Criteria: Presence of any condition that may disrupt and/or increase permeability of the BBB, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, acute central nervous system (CNS) infection, CNS tumor, autoimmune disease affecting the CNS, or CNS inflammatory Current significant illness, pathology or physical examination or vital signs measurement-findings that could potentiate any adverse pharmacological event associated with a vasodilatory drug or any pathology that, in the opinion of the investigator, might confound the interpretation of the results of the study Known hypersensitivity to adenosine, dipyridamole or aminophylline Presence of any contraindications to exercise stress testing History of New York Heart Association Class III or IV Congestive Heart Failure (CHF) Any major surgery within 4 weeks prior to enrollment or planned within 2 weeks following completion of the 2-week telephone follow-up assessment Inability to tolerate IV medication. History of drug or alcohol abuse within the last year Participation in any investigational drug, device, or placebo study within 6 months prior to study enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cesare Orlandi, MD
Organizational Affiliation
Lantheus Medical Imaging
Official's Role
Study Director
Facility Information:
Facility Name
Silicon Valley Medical Imaging
City
Fremont
State/Province
California
ZIP/Postal Code
94538
Country
United States
Facility Name
Scripps Memorial Hospital
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA Medical Plaza
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Radiological Associates of Sacramento
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
VA Healthcare System San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Facility Name
Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
05102-5037
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Primary Care Cardiology Research, Inc
City
Ayer
State/Province
Massachusetts
ZIP/Postal Code
01432
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Cardiovascular Consultants
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64101
Country
United States
Facility Name
Saint Louis University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Medicine and Dentistry of New Jersey
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07107
Country
United States
Facility Name
Holy Name Hospital
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
St. Francis Hospital
City
Roslyn
State/Province
New York
ZIP/Postal Code
11576
Country
United States
Facility Name
University Hospital Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Midwest Cardiology Research Foundation
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
Facility Name
Mountain States Health Alliance
City
Johnson City
State/Province
Tennessee
ZIP/Postal Code
37604
Country
United States
Facility Name
East Tennessee Clinical Research Institute
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
27934
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15261128
Citation
Bateman TM. Cardiac positron emission tomography and the role of adenosine pharmacologic stress. Am J Cardiol. 2004 Jul 22;94(2A):19D-24D; discussion 24D-25D. doi: 10.1016/j.amjcard.2004.04.013.
Results Reference
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PubMed Identifier
14569247
Citation
Beller GA. First annual Mario S. Verani, MD, Memorial lecture: clinical value of myocardial perfusion imaging in coronary artery disease. J Nucl Cardiol. 2003 Sep-Oct;10(5):529-42. doi: 10.1016/s1071-3581(03)00655-x.
Results Reference
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PubMed Identifier
14752475
Citation
Beller GA, Bergmann SR. Myocardial perfusion imaging agents: SPECT and PET. J Nucl Cardiol. 2004 Jan-Feb;11(1):71-86. doi: 10.1016/j.nuclcard.2003.12.002. No abstract available.
Results Reference
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PubMed Identifier
10736294
Citation
Beller GA, Zaret BL. Contributions of nuclear cardiology to diagnosis and prognosis of patients with coronary artery disease. Circulation. 2000 Mar 28;101(12):1465-78. doi: 10.1161/01.cir.101.12.1465. No abstract available.
Results Reference
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PubMed Identifier
8294691
Citation
Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging: results from the Adenoscan Multicenter Trial Registry. J Am Coll Cardiol. 1994 Feb;23(2):384-9. doi: 10.1016/0735-1097(94)90424-3.
Results Reference
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PubMed Identifier
7744540
Citation
Guideri F, Ferber D, Galgano G, Isidori S, Blardi P, Pasini FL, Di Perri T. QTc interval prolongation during infusion with dipyridamole or adenosine. Int J Cardiol. 1995 Jan 27;48(1):67-73. doi: 10.1016/0167-5273(94)02209-2.
Results Reference
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PubMed Identifier
18022101
Citation
Glover DK, Gropler RJ. Journey to find the ideal PET flow tracer for clinical use: are we there yet? J Nucl Cardiol. 2007 Nov-Dec;14(6):765-8. doi: 10.1016/j.nuclcard.2007.09.019. No abstract available.
Results Reference
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PubMed Identifier
17174798
Citation
Henzlova MJ, Cerqueira MD, Mahmarian JJ, Yao SS; Quality Assurance Committee of the American Society of Nuclear Cardiology. Stress protocols and tracers. J Nucl Cardiol. 2006 Nov;13(6):e80-90. doi: 10.1016/j.nuclcard.2006.08.011. No abstract available.
Results Reference
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PubMed Identifier
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Citation
Miyamoto MI, Vernotico SL, Majmundar H, Thomas GS. Pharmacologic stress myocardial perfusion imaging: a practical approach. J Nucl Cardiol. 2007 Apr;14(2):250-5. doi: 10.1016/j.nuclcard.2007.01.006. No abstract available. Erratum In: J Nucl Cardiol. 2007Jul;14(4):628.
Results Reference
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Development of 1-Day Rest/Stress Cardiac PET Perfusion Imaging Protocol of BMS747158

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