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

NCT00849108 | Completed Phase 2 Results DMC

• 1 other identifier: BMS747158-201
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 24

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

Cohort 1: dose range and dose interval

EXPERIMENTAL

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

Cohort 2: Pharm&exercise stress Efficacy

EXPERIMENTAL

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

Interventions

BMS747158 DRUG

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.

Also known as: There are no other names

Cohort 1: dose range and dose interval; Cohort 2: Pharm&exercise stress Efficacy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Lantheus Medical Imaging: lead

Study Sites (24)

Silicon Valley Medical Imaging

Fremont, California, 94538, United States

Location

Scripps Memorial Hospital

La Jolla, California, 92037, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Medical Plaza

Los Angeles, California, 90095, United States

Location

Radiological Associates of Sacramento

Sacramento, California, 95816, United States

Location

VA Healthcare System San Diego

San Diego, California, 92161, United States

Location

Hartford Hospital

Hartford, Connecticut, 05102-5037, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Primary Care Cardiology Research, Inc

Ayer, Massachusetts, 01432, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Cardiovascular Consultants

Kansas City, Missouri, 64101, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Medicine and Dentistry of New Jersey

Newark, New Jersey, 07107, United States

Location

Holy Name Hospital

Teaneck, New Jersey, 07666, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

St. Francis Hospital

Roslyn, New York, 11576, United States

Location

University Hospital Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Midwest Cardiology Research Foundation

Columbus, Ohio, 43214, United States

Location

Mountain States Health Alliance

Johnson City, Tennessee, 37604, United States

Location

East Tennessee Clinical Research Institute

Knoxville, Tennessee, 27934, United States

Location

Related 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. doi: 10.1016/j.amjcard.2004.04.013.

  PMID: 15261128 BACKGROUND

• 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.

  PMID: 14569247 BACKGROUND

• 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.

  PMID: 14752475 BACKGROUND

• 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.

  PMID: 10736294 BACKGROUND

• 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.

  PMID: 8294691 BACKGROUND

• 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.

  PMID: 7744540 BACKGROUND

• 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.

  PMID: 18022101 BACKGROUND

• 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.

  PMID: 17174798 BACKGROUND

• 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.

  PMID: 17386388 BACKGROUND

MeSH Terms

Conditions

Ischemia; Coronary Artery Disease

Interventions

BMS 747158-02

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Cesare Orlandi, MD, Chief Medical Officer
• Organization: Lantheus Medical Imaging

cesare.orlandi@lantheus.com

978-671-8686

Study Officials

• Cesare Orlandi, MD

  Lantheus Medical Imaging

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2009
• First Posted: February 23, 2009
• Study Start: January 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: October 14, 2015
• Results First Posted: January 19, 2015

Record last verified: 2012-04

Locations

US (24)