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

Phase 2

Completed

• Conditions: Ischemia
• Interventions: Drug: BMS747158

• Registration Number: NCT00849108
• Lead Sponsor: Lantheus Medical Imaging

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-01-05
• Study First Submitted QC: 2009-02-20
• Study First Posted: 2009-02-23
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Status Verified: 2012-04
• Results First Submitted: 2014-10-30
• Results First Submitted QC: 2015-01-09
• Results First Posted: 2015-01-19
• Last Update Submitted: 2015-10-12
• Last Update Posted: 2015-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 176

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: dose range and dose interval	BMS747158	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.
Cohort 2: Pharm&exercise stress Efficacy	BMS747158	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.

Primary Outcome Measures

Name	Time	Method
Cohort 1: Determination of Rest Dose: Dose Acquistion Time Product	Dosing visit	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	Dosing visit	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	Dosing visit	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	Dosing Visit	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.

Trial Locations

Locations (24)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Brigham & Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University Hospital Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

VA Healthcare System San Diego; 🇺🇸 San Diego, California, United States

Primary Care Cardiology Research, Inc; 🇺🇸 Ayer, Massachusetts, United States

Midwest Cardiology Research Foundation; 🇺🇸 Columbus, Ohio, United States

Radiological Associates of Sacramento; 🇺🇸 Sacramento, California, United States

University of Medicine and Dentistry of New Jersey; 🇺🇸 Newark, New Jersey, United States

Mountain States Health Alliance; 🇺🇸 Johnson City, Tennessee, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Holy Name Hospital; 🇺🇸 Teaneck, New Jersey, United States

St. Francis Hospital; 🇺🇸 Roslyn, New York, United States

Cardiovascular Consultants; 🇺🇸 Kansas City, Missouri, United States

East Tennessee Clinical Research Institute; 🇺🇸 Knoxville, Tennessee, United States

Silicon Valley Medical Imaging; 🇺🇸 Fremont, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Scripps Memorial Hospital; 🇺🇸 La Jolla, California, United States

UCLA Medical Plaza; 🇺🇸 Los Angeles, California, United States

Saint Louis University; 🇺🇸 St. Louis, Missouri, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States