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

Ischemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00849108
• Other study ID #: BMS747158-201
• Status: Completed
• Phase: Phase 2
• First received: January 5, 2009
• Last updated: October 12, 2015
• Start date: January 2009
• Est. completion date: June 2010

Study information

• Verified date: April 2012
• Source: Lantheus Medical Imaging
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Ischemia

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Primary Care Cardiology Research, Inc	Ayer	Massachusetts
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University Hospital Case Medical Center	Cleveland	Ohio
United States	Midwest Cardiology Research Foundation	Columbus	Ohio
United States	Silicon Valley Medical Imaging	Fremont	California
United States	Hartford Hospital	Hartford	Connecticut
United States	Mountain States Health Alliance	Johnson City	Tennessee
United States	Cardiovascular Consultants	Kansas City	Missouri
United States	East Tennessee Clinical Research Institute	Knoxville	Tennessee
United States	Scripps Memorial Hospital	La Jolla	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA Medical Plaza	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	St. Francis Hospital	Roslyn	New York
United States	Radiological Associates of Sacramento	Sacramento	California
United States	VA Healthcare System San Diego	San Diego	California
United States	Saint Louis University	St. Louis	Missouri
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Holy Name Hospital	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Lantheus Medical Imaging

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. Review. — View Citation

Beller GA, Bergmann SR. Myocardial perfusion imaging agents: SPECT and PET. J Nucl Cardiol. 2004 Jan-Feb;11(1):71-86. Review. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Review. Erratum in: J Nucl Cardiol. 2007Jul;14(4):628. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No