a dose titration study to assess the effects of sar407899 in patients with mva and/or persistent stable angina despite angiographically successful pci

Conditions: Microvascular Coronary Artery Disease

Summary: 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.

the total duration of study per participant was: - up to 9 weeks for participants with previous coronary artery angiography or coronary computed tomography angiography (ccta) within 24 months prior to screening with up to 4 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration. or - up to 11 weeks for participants with previous coronary artery angiography or ccta between 24 months and 5 years prior to screening who need ccta during screening period with up to 6 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration.

Eligibility criteria:
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 (\ 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.