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

Launched by SANOFI · Jul 31, 2017

Keywords

ClinConnect Summary

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 perio...

Gender

ALL

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 (\<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.