Status:
TERMINATED
A Dose Titration Study to Assess the Effects of SAR407899 in Patients With MVA and/or Persistent Stable Angina Despite Angiographically Successful PCI
Lead Sponsor:
Sanofi
Conditions:
Microvascular Coronary Artery Disease
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
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 ang...
Detailed Description
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 ...
Eligibility Criteria
Inclusion
- 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.
Exclusion
Key Trial Info
Start Date :
October 12 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 23 2018
Estimated Enrollment :
10 Patients enrolled
Trial Details
Trial ID
NCT03236311
Start Date
October 12 2017
End Date
July 23 2018
Last Update
March 24 2022
Active Locations (10)
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1
Investigational Site Number 8400003
Los Angeles, California, United States, 90048
2
Investigational Site Number 8400001
Jacksonville, Florida, United States, 32209
3
Investigational Site Number 8400013
Wellington, Florida, United States, 33449
4
Investigational Site Number 8400008
Baltimore, Maryland, United States, 21287