Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging
Condition: Myocardial Perfusion Imaging; Myocardial Ischemia
MeSH terms: Myocardial Ischemia; Ischemia
Intervention: Ranolazine; Placebo to match ranolazine; SPECT MPI; Exercise
Intervention description: One 500 mg tablet in the evening on Day 1 of the period
One 500 mg tablet, twice daily on Days 2-3 of the period
Two 500 mg tablets (1000 mg total), twice daily from Day 4 to the end of the period (Day 15 ± 2 days); Placebo to match ranolazine administered in the same form and frequency as the active drug.; Gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to confirm the presence of reversible exercise-induced left ventricular perfusion defect size (PDS) performed within 12 weeks prior to baseline or at the baseline visit, and at the end-of-period 1 and end-of-period 2 visits.; Treadmill stress test
Intervention MeSH terms: Ranolazine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SPECT MPI

Summary:

      This study enrolled participants with documented exercise-induced myocardial ischemia in
      order to evaluate whether ranolazine, when taken prior to exercise, can improve blood flow to
      the heart (myocardial perfusion), as assessed by exercise-induced myocardial perfusion defect
      size (PDS) and total perfusion deficit (TPD), using gated single photon emission computed
      tomography (SPECT) myocardial perfusion imaging (MPI).

      This was a 2-period crossover study. The last dose of each period must have been taken 3-4
      hours prior to conduct of the exercise SPECT MPI. After the research exercise SPECT MPI was
      performed at the end of Period 1, participants discontinued the treatment they were
      randomized to for that period and began the other treatment in Period 2.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Exercise SPECT MPI study (stress and rest) showing at least 10% reversible myocardial
             ischemia (as confirmed by the core nuclear laboratory using Corridor4DM imaging
             software) performed not more than 12 weeks prior to screening, OR

          -  Exercise SPECT MPI study (stress and rest) conducted during screening (after
             consultation with the Medical Monitor and after informed consent was obtained) showing
             at least 10% reversible myocardial ischemia (as confirmed by the core nuclear
             laboratory)

          -  Stable antianginal medical therapy (excluding short-acting nitroglycerin)

        Key Exclusion Criteria:

          -  Left bundle branch block

          -  Automated implantable defibrillator and/or pacemaker (selected subjects with permanent
             pacemakers who had an intact sinus mechanism may have been included following
             consultation with the Medical Monitor)

          -  Intervening coronary revascularization between the time of qualifying exercise SPECT
             MPI study and randomization

          -  Acute myocardial infarction (MI) within 60 days prior to screening or at any time
             after the qualifying exercise SPECT MPI study, or MI undergoing staged intervention
             during a subject's participation in the trial

          -  Unstable angina within 30 days prior to screening, or at any time after the qualifying
             exercise SPECT MPI study

          -  Coronary artery bypass graft surgery within 60 days prior to screening or at any time
             after the qualifying exercise SPECT MPI study, or percutaneous coronary intervention
             within 30 days prior to screening or at any time after the qualifying exercise SPECT
             MPI study

          -  Anticipated coronary revascularization during the trial period

          -  Cerebrovascular attack or transient ischemic attack within 90 days prior to screening

          -  History of serious arrhythmias

          -  Current atrial fibrillation or atrial flutter

          -  QTc interval > 500 milliseconds

          -  Diagnosed as having New York Heart Association Class III or IV heart failure

          -  Inability to exercise or exercise limitation due to other comorbidities that may have
             interfered with ability to perform required exercise SPECT MPI study

          -  Body mass index greater than or equal to 38 kg/m^2 (may have been up to 40 kg/m^2
             after consultation with the Medical Monitor)

          -  Any absolute contraindications to exercise stress testing