A Dose Titration Study to Assess the Effects of SAR407899 in Patients With Microvascular Angina and/or Persistent Stable Angina Despite Angiographically Successful Elective PCI

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 16-009677
    NCT ID: NCT03236311
    Sponsor Protocol Number: ACT14656

About this study

The Primary Objective of this study: -To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in patients with microvascular angina and/or persistent stable angina despite angiographically successful elective percutaneous coronary intervention (PCI). The Secondary Objectives of this study are: - To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire physical limitation domain (SAQ-PL) in patients with microvascular angina and/or persistent stable angina despite angiographically successful elective PCI. - To assess the safety of SAR407899 in patients with microvascular angina and/or persistent stable angina despite angiographically successful elective PCI with a focus on identified risks such as hypotension and orthostatic hypotension. - To assess SAR407899 plasma concentrations in microvascular angina patients and/or persistent stable angina despite angiographically successful elective PCI.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria :

  • Male or female patient not at childbearing potential ≥18 year-old or legal age of majority.
  • Female patient if she has undergone sterilization at least 3 months earlier or is postmenopausal.
  • Post-menopausal status is defined by having no menses for 12 months without an alternative medical cause.
  • In females not treated with hormonal replacement therapy (HRT), menopausal status is confirmed by a high follicle stimulating hormone (FSH) level greater than 40 IU/L.
  • In females on HRT and whose menopausal status is in doubt (ie, in women aged less than 45 years), a highly effective contraception methods will be required. Contraception should be used during the whole study and for at least seven days corresponding to time needed to eliminate study treatment.
  • Symptomatic stable angina pectoris (typical or atypical symptoms with at least once weekly episodes),
  • Electrocardiogram (ECG) evidence of ischemia with ST-segment depression during a symptom limited exercise test or non-invasive evidence of ischemia [echo, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), positron emission tomography (PET)] within previous 12 months.
  • Patients with "normal" or "subnormal" (<50% stenosis) coronary arteries or intermediate stenosis (between 50 and 70%) should have fractional flow reserve (FFR) >0.80 on angiogram documented within the previous 12 months. In patients with stenting, a minimum diameter stenosis of <10% is required.

or Coronary computed tomography angiography (CCTA) without regional abnormal perfusion defects within 12 months in patients without previous PCI.

- Baseline global CFR (measured during the study) assessed by 13N-ammonia or 82rubidium PET scan <2.0.

Exclusion Criteria:

  • Esophageal dysmotility or esophagitis.
  • Any use of long-acting nitrates and/or calcium channel blockers (CCBs) and/or phosphodiesterase type 5 (PDE5) inhibitors within one week prior to baseline PET scan or anticipated to be used during the study.
  • Patients with acute coronary syndrome (ACS) [myocardial infarction (MI) and/or unstable angina] in previous 3 months.
  • Unsuccessful or incomplete coronary revascularization with residual obstructive stenosis or coronary artery disease (CAD) progression in native vessels as documented on invasive coronary angiography (≥50% stenosis) within 12 months of enrollment.
  • Patients with history of coronary artery bypass grafting (CABG).
  • Percutaneous coronary intervention performed at the time of an ACS (MI or unstable angina).
  • Recent elective PCI within the past 3 months.
  • Contraindication to vasodilator stress PET scan.
  • Regional local flow abnormal perfusion defects at baseline PET scan.
  • Recent (≤3 months) major surgery (ie, valvular surgery, surgery for congenital heart disease), stroke, transient ischemic attack (TIA), sustained ventricular arrhythmia, clinically significant structural heart disease (moderate-severe valvular disease, hypertrophic cardiomyopathy, congenital heart disease, pulmonary hypertension).
  • Patients with cardiac conduction abnormalities (second or third degree atrioventricular [AV] block, sick sinus syndrome, symptomatic bradycardia, sinus node disease).
  • History of known carotid stenosis.
  • Contraindication or known hypersensitivity to adenosine (or regadenoson).
  • Contraindication to aminophylline.
  • Ongoing dipyridamole treatment.
  • Inability to discontinue treatment with methylxanthines treatment within 24 hours prior to PET scan.
  • Patient unable to read, understand and fill a questionnaire without any help (eg, partially visually impaired or blind).
  • Systolic Blood Pressure (SBP) <120 mmHg at baseline.
  • Presence at baseline of symptomatic orthostatic hypotension (SBP decrease of 20 mmHg or more at Minute 3 and Minute 5 between seated and standing position), or asymptomatic orthostatic hypotension with a decrease in SBP equal or greater than 30 mmHg at Minute 3 and Minute 5 when changing from the seated to the standing position.
  • Renal impairment [estimated glomerular filtration rate (eGFR) <50 milliliter (mL)/min/1.73m2 at screening and baseline].
  • Drug-induced liver injury related criteria:
  • Underlying hepatobiliary disease,
  • ALT >3 times the upper limit of normal (ULN).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Amir Lerman, M.D.

Contact us for the latest status

Contact information:

Alysha Bleifus

(507)255-7142

Bleifus.Alysha@mayo.edu

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CLS-20361373

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