A randomized, double-blind, placebo-controlled parallel arm dose titration study to assess the effects of SAR407899 in patients with microvascular angina and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI)
- Conditions
- chestpain due to narrowed heart vesselsmicrovascular angina10082206
- Registration Number
- NL-OMON46635
- Lead Sponsor
- Sanofi-aventis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 5
- 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),;- Electrocardiogram (ECG) evidence of ischemia with ;ST-segment depression during a symptom limited exercise test or non-invasive evidence of ischemia [echo, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), positron emission tomography (PET)] within previous 12 months.;- Patients with *normal* or *subnormal* (<50% stenosis) coronary arteries or intermediate stenosis (between 50 and 70%) should have fractional flow reserve (FFR) >0.80 on angiogram documented within the previous 12 months. In patients with stenting, a minimum diameter stenosis of <10% is required.;or;Coronary computed tomography angiography (CCTA) without regional abnormal perfusion defects within 12 months in patients without previous PCI.
Or CCTA performed during screening period, with finding of non-obstructive coronary arteries, in patients diagnosed with 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 CFR (measured during the study) assessed by 13N-ammonia or 82rubidium PET scan <2.0.
- Esophageal dysmotility or esophagitis.;- Any use of long-acting nitrates and/or calcium channel blockers (CCBs) and/or phosphodiesterase type 5 (PDE5) inhibitors within one week prior to baseline PET scan or anticipated to be used during the study.;- 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 12 months of enrollment.;- Patients with history of coronary artery bypass grafting (CABG).;- Percutaneous coronary intervention performed at the time of an ACS (MI or unstable angina) in the previous 12 months.;- Recent elective PCI within the past 3 months.;- Contraindication to vasodilator stress PET scan and or CCTA if CCTA needed during screening.;- Regional local flow abnormal perfusion defects at baseline PET scan.;- 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).;- 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 patient with previous symptoms;- Contraindication or known hypersensitivity to adenosine (or regadenoson).;- Contraindication to aminophylline.;- Ongoing dipyridamole treatment.;- 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) <120 mmHg at baseline.;- Presence at baseline of symptomatic orthostatic hypotension (SBP decrease of 20 mmHg or more at Minute 3 and 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 and Minute 5 when changing from the seated to the standing position.;- Renal impairment [estimated glomerular filtration rate (eGFR) <50 milliliter (mL)/min/1.73m2 at screening and baseline].;- Drug-induced liver injury related criteria: ;- Underlying hepatobiliary disease, ;- ALT >3 times the upper limit of normal (ULN).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change from baseline to Week 4 in uncorrected global CFR assessed by<br /><br>13N-ammonia PET scan.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary efficacy endpoint:<br /><br>* Change from baseline to Week 4 on angina-induced physical limitation using<br /><br>SAQ-PL (disease-specific health-related quality of life).<br /><br><br /><br>Exploratory endpoints:<br /><br>* Rate of diary angina episodes at baseline and Week 4<br /><br>* Rate of diary angina episodes requiring use of short-acting nitrates at<br /><br>baseline and Week 4<br /><br>* Change from baseline to Week 4 in the other dimensions of the SAQ.<br /><br>* Change from baseline to Week 4 in the SAQ-7 score.<br /><br>* Patients* perceptions of treatment and symptoms assessed at baseline and Week<br /><br>4.<br /><br><br /><br>Safety:<br /><br>* Adverse events (AEs) / treatment-emergent adverse events (TEAEs).<br /><br>* Blood pressure and orthostatic blood pressure.<br /><br>* Blood creatinine and cystatin C.<br /><br><br /><br>Pharmacokinetics:<br /><br>* Peak and trough SAR407899 concentrations at specific timepoints.</p><br>