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