Microvascular coronary artery disease MedDRA version: 20.0 Level: PT Classification code 10072685 Term: Microvascular coronary artery disease System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Code: SAR407899A
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: RHO-KINASE INHIBITOR
CAS Number: 923262-96-8
Current Sponsor code: SAR407899A
Concentration unit: mg milligram(s)
Conce
Sponsors
SANOFI-AVENTIS RECHERCHE ET DEVELOPPEMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female patient not at childbearing potential =18 year-old or legal age of majority. - Female patient if she has undergone sterilization at least 3 months earlier or is postmenopausal. - Post-menopausal status is defined by having no menses for 12 months without an alternative medical cause. - In females not treated with hormonal replacement therapy (HRT), menopausal status is confirmed by a high follicle stimulating hormone (FSH) level greater than 40 IU/L. - In females on HRT and whose menopausal status is in doubt (ie, in women aged less than 45 years), a highly effective contraception methods will be required. Contraception should be 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 biweekly episodes over the past month). - Patients with non-obstructive (0.80 or instantaneous wave-free ratio (iFR) >0.89 on angiogram, documented within the previous 24 months*. In patients with stenting, a minimum diameter stenosis of =65 years) yes F.1.3.1 Number of subjects for this age range 77
Exclusion criteria
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. - Patients 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. - Patients with history of coronary artery bypass grafting (CABG). - Recent (=3 months) major surgery (ie, 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 coronary computed tomography angiography (CCTA) demonstrates non-obstructive coronary arteries or if the regional local flow abnormal perfusion defect on PET scan is consistent with previous studies then patient qualifies for the study. - Patients with cardiac conduction abnormalities (second or third degree atrioventricular [AV] block, sick sinus syndrome, symptomatic bradycardia, sinus node disease) except in patients fitted with a functioning pacemaker. - History or known carotid stenosis: - Carotid stenosis (>50%) or - History of carotid stenosis in patients 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. - Patient unable to read, understand and fill a questionnaire without any help (eg, partially visually impaired or blind). - Systolic blood pressure (SBP) 3 times the upper limit of normal (ULN).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in patients with microvascular angina (MVA) and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI).;Secondary Objective: -To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire physical limitation domain (SAQ-PL) in patients with MVA and/or persistent stable angina despite angiographically successful PCI. -To assess the safety of SAR407899 in patients 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 patients and/or persistent stable angina despite angiographically successful PCI. ;Primary end point(s): Change in uncorrected global coronary flow reserve (CFR): Absolute change from baseline to Week 4 in uncorrected global CFR assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.;Timepoint(s) of evaluation of this end point: From baseline to Week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in angina-induced physical limitation: Absolute change from baseline to Week 4 on angina-induced physical limitation using Seattle Angina Questionnaire physical limitation (SAQ-PL) scale (disease-specific health-related quality of life). 2. Safety: Adverse events (AEs) / treatment-emergent adverse events (TEAEs): Percentage of patients with TEAEs, treatment emergent serious adverse events, TEAEs leading to treatment discontinuation, and treatment emergent adverse events of specific interest (AESIs). 3. Safety: Blood pressure (BP) and orthostatic blood pressure: Description of BP and orthostatic BP during the course of the study, and percentage of patients with hypotension, orthostatic hypotension. 4. Pharmacokinetics: SAR407899 plasma concentration level SAR407899 concentrations at specific time points.;Timepoint(s) of evaluation of this end point: 1. From baseline to Week 4 2. Up to 9 weeks 3. From Day 1 to Week 5 4. From Day 1 to Week 4 | — |
Countries
Denmark, Korea, Republic of, Netherlands, Spain, Sweden, United States
Contacts
Public ContactCountry Team Manager Sweden
Sanofi AB
Outcome results
None listed