A Dose Titration Study to Assess the Effects of SAR407899 in Patients with Microvascular Angina and/or Persistent Stable Angina despite Angiographically Successful Elective Percutaneous Coronary Intervention (PCI)
- Conditions
- Microvascular coronary artery diseaseMedDRA version: 20.0 Level: PT Classification code 10072685 Term: Microvascular coronary artery disease System Organ Class: 10007541 - Cardiac disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-000629-38-NL
- Lead Sponsor
- SANOFI-AVENTIS RECHERCHE ET DEVELOPPEMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
- 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 183
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 77
- 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).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method