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Sponsor: Sanofi
Conditions: Microvascular Coronary Artery Disease
Interventions: SAR407899, Placebo, Adenosine, Regadenoson, 13N-ammonia
Countries: United States, Denmark, Netherlands, South Korea, Sweden
Primary Objective: To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in participants with microvascular angina (MVA) and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI). Secondary Objectives: * To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire physical limitation scale (SAQ-PL) in participants with MVA and/or persistent stable angina despite angiographically successful PCI. * To assess the safety of SAR407899 in participants with MVA and/or persistent stable angina despite angiographically successful PCI with a focus on identified risks such as hypotension and orthostatic hypotension. * To assess SAR407899 plasma concentrations in MVA participants and/or persistent stable angina despite angiographically successful PCI.
Sex: ALL
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
Inclusion criteria: * Male or female participants not at childbearing potential \>=18 year-old or legal age of majority. * Female participant if she has undergone sterilization at least 3 months earlier or was post-menopausal. * Post-menopausal status was defined by having no menses for 12 months without an alternative medical cause. * In females not treated with hormonal replacement therapy (HRT), menopausal status was confirmed by a high follicle stimulating hormone (FSH) level greater than 40 international units per litre (IU/L). * In females on HRT and whose menopausal status was in doubt (i.e. in women aged less than 45 years), a highly effective contraception methods was required. Contraception was 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 an average of at least bi-weekly episodes over the past month). * Participants with non-obstructive (\<50% stenosis) coronary arteries or intermediate stenosis (between 50 and 70%) should have fractional flow reserve (FFR) \>0.80 or instantaneous wave-free ratio (iFR) \>0.89 on angiogram, documented within the previous 24 months\*. In participants with stenting, a minimum diameter stenosis of \<10% is required. or Coronary computed tomography angiography (CCTA) with finding of non-obstructive coronary arteries within the past 24 months\* in participants without previous percutaneous coronary intervention (PCI). \*Note: in cases of clinically suspected progression of atherosclerosis as per the Investigator, a more contemporary (i.e., 6 months) evidence should be provided. or CCTA performed during screening period, with finding of non-obstructive coronary arteries, in participants diagnosed with microvascular angina (MVA) and stable angina without previous PCI who did not have a coronary angiogram or CCTA in the previous 24 months but between 24 months to 5 years. \- Baseline global coronary flow reserve (CFR) (measured during the study) assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan \<2.0. Exclusion criteria: * Any use of nitrates (except short-acting nitrates) and/or dipyridamole and/or phosphodiesterase type 5 (PDE 5) inhibitors within one week prior to baseline PET scan or anticipated to be used during the study. * Esophageal dysmotility or esophagitis. * Participants 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 24 months of enrollment. * Percutaneous coronary intervention performed at the time of an ACS (MI or unstable angina) in the previous 12 months. * Recent PCI within the past 3 months. * Participants with history of coronary artery bypass grafting (CABG). * Recent (\<=3 months) major surgery (i.e. 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). * Regional local flow abnormal perfusion defects at baseline PET scan\*. \*Note: if contemporary evidence with invasive coronary angiography or CCTA demonstrates non-obstructive coronary arteries or if the regional local flow abnormal perfusion defect on PET scan is consistent with previous studies then participant qualifies for the study. * Participants with cardiac conduction abnormalities (second or third degree atrioventricular \[AV\] block, sick sinus syndrome, symptomatic bradycardia, sinus node disease) except in participants fitted with a functioning pacemaker. * History or known carotid stenosis: * Carotid stenosis (\>50%) or * History of carotid stenosis in participants with previous symptoms. * Contraindication or known hypersensitivity to adenosine or regadenoson. * Contraindication to aminophylline. * Contraindication to vasodilator stress PET scan and/or CCTA if CCTA needed during screening. * Inability to discontinue treatment with methylxanthines treatment within 24 hours prior to PET scan. * Participant unable to read, understand and fill a questionnaire without any help (eg, partially visually impaired or blind). * Systolic blood pressure (SBP) \<110 millimeter of mercury (mmHg) at baseline. * Presence at baseline of symptomatic orthostatic hypotension (SBP decrease of 20 mmHg or more at Minute 3 or 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 or Minute 5 when changing from the seated to the standing position. * Renal impairment with estimated glomerular filtration rate (eGFR) \<50 milliliter/minute/1.73 square meter (mL/min/1.73 m\^2) at screening and baseline. * Drug-induced liver injury related criteria: * Underlying hepatobiliary disease. * Alanine Aminotransferase (ALT) \>3 times the upper limit of normal (ULN). The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
- Los Angeles, California, United States
- Jacksonville, Florida, United States
- Wellington, Florida, United States
- Baltimore, Maryland, United States
- Boston, Massachusetts, United States
- Philadelphia, Pennsylvania, United States
- København NV, Denmark
- Nijmegen, Netherlands
- Seoul, South Korea
- Lund, Sweden