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

Stopped early · Phase 2 · Has a placebo group

Conditions studied: Microvascular Coronary Artery Disease

In brief

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.

Key facts

Study ID

NCT03236311

Run by

Sanofi

People needed

10

Starts

2017-10-12

Expected to finish

2018-07-23

Last updated by the study team

2022-03-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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).

Where it is running

• Investigational Site Number 8400003 — Los Angeles, California, United States
• Investigational Site Number 8400001 — Jacksonville, Florida, United States
• Investigational Site Number 8400013 — Wellington, Florida, United States
• Investigational Site Number 8400008 — Baltimore, Maryland, United States
• Investigational Site Number 8400006 — Boston, Massachusetts, United States
• Investigational Site Number 8400010 — Philadelphia, Pennsylvania, United States
• Investigational Site Number 2080001 — København NV, Denmark
• Investigational Site Number 5280001 — Nijmegen, Netherlands
• Investigational Site Number 4100002 — Seoul, South Korea
• Investigational Site Number 7520001 — Lund, Sweden

Full record on ClinicalTrials.gov

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