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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lantheus Medical Imaging
ClinicalTrials.gov Identifier:
NCT00849108
First received: January 5, 2009
Last updated: January 9, 2015
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Ischemia
Drug: BMS747158
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Lantheus Medical Imaging:

Primary Outcome Measures:
  • Cohort 1: Determination of Rest Dose: Dose Acquistion Time Product [ Time Frame: Dosing visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: Dosing visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: Dosing visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: Dosing Visit ] [ Designated as safety issue: No ]
    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.


Enrollment: 176
Study Start Date: January 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: There are no other names

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
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00849108

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

Publications:

Responsible Party: Lantheus Medical Imaging
ClinicalTrials.gov Identifier: NCT00849108     History of Changes
Other Study ID Numbers: BMS747158-201
Study First Received: January 5, 2009
Results First Received: October 30, 2014
Last Updated: January 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Lantheus Medical Imaging:
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

ClinicalTrials.gov processed this record on June 30, 2015