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

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

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.

Study Overview

• Status: Completed
• Conditions: Ischemia
• Intervention / Treatment: Drug: BMS747158

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

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fremont, California, United States, 94538
      • Silicon Valley Medical Imaging
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital
    • Los Angeles, California, United States, 90095
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Medical Plaza
    • Sacramento, California, United States, 95816
      • Radiological Associates of Sacramento
    • San Diego, California, United States, 92161
      • VA Healthcare System San Diego
  • Connecticut
    • Hartford, Connecticut, United States, 05102-5037
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Massachusetts
    • Ayer, Massachusetts, United States, 01432
      • Primary Care Cardiology Research, Inc
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women'S Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Kansas City, Missouri, United States, 64101
      • Cardiovascular Consultants
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St. Louis, Missouri, United States, 63110
      • Saint Louis University
  • New Jersey
    • Newark, New Jersey, United States, 07107
      • University of Medicine and Dentistry of New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital Case Medical Center
    • Columbus, Ohio, United States, 43214
      • MidWest Cardiology Research Foundation
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • Mountain States Health Alliance
    • Knoxville, Tennessee, United States, 27934
      • East Tennessee Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: dose range and dose interval; 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.	Drug: BMS747158; 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.; Other Names: There are no other names
Experimental: Cohort 2: Pharm&exercise stress Efficacy; 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.	Drug: BMS747158; 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.; Other Names: There are no other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Dosing visit
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.	Dosing visit
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.	Dosing visit
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.	Dosing Visit

Collaborators and Investigators

• Sponsor: Lantheus Medical Imaging
• Investigators: Study Director: Cesare Orlandi, MD, Lantheus Medical Imaging

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 5, 2009
• First Submitted That Met QC Criteria: February 20, 2009
• First Posted (Estimate): February 23, 2009

Study Record Updates

• Last Update Posted (Estimate): October 14, 2015
• Last Update Submitted That Met QC Criteria: October 12, 2015
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Coronary artery disease; PET imaging; Myocardial Perfusion; SPECT imaging; 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
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: BMS747158-201