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

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ClinicalTrials.gov Identifier: NCT03236311
Recruitment Status : Terminated ((Recruitment was early terminated due to slow recruitment. Not linked to any safety concern.))
First Posted : August 1, 2017
Last Update Posted : January 14, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary 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 Objectives:

  • 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.

Condition or disease Intervention/treatment Phase
Microvascular Coronary Artery Disease Drug: SAR407899 Drug: Placebo Drug: Adenosine Drug: Regadenoson Drug: 13N-ammonia Drug: 82Rubidium Phase 2

Detailed Description:

The total duration of study per subject is:

- up to 9 weeks for patients 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 patients 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 period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Parallel Arm Dose Titration Study to Assess the Effects of SAR407899 in Patients With Microvascular Angina (MVA) and/or Persistent Stable Angina Despite Angiographically Successful Elective Percutaneous Coronary Intervention (PCI)
Actual Study Start Date : October 12, 2017
Actual Primary Completion Date : July 23, 2018
Actual Study Completion Date : July 23, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angina

Arm Intervention/treatment
Experimental: SAR407899
SAR407899 with dose titration over 4 weeks administration
Drug: SAR407899
Pharmaceutical form: Capsule Route of administration: Oral

Drug: Adenosine
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Regadenoson
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: 13N-ammonia
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: 82Rubidium
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Placebo Comparator: Placebo
Matching placebo for 4 weeks
Drug: Placebo
Pharmaceutical form: Capsule Route of administration: Oral

Drug: Adenosine
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Regadenoson
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: 13N-ammonia
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: 82Rubidium
Pharmaceutical form: Solution for injection Route of administration: Intravenous




Primary Outcome Measures :
  1. Change in uncorrected global coronary flow reserve (CFR) [ Time Frame: From baseline to Week 4 ]
    Absolute change from baseline to Week 4 in uncorrected global CFR assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan


Secondary Outcome Measures :
  1. Change in angina-induced physical limitation [ Time Frame: From baseline to Week 4 ]
    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) [ Time Frame: Up to 9 weeks ]
    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 [ Time Frame: From Day 1 to Week 5 ]
    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 [ Time Frame: From Day 1 to Week 4 ]
    SAR407899 concentrations at specific time points



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 post-menopausal.
  • 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 bi-weekly episodes over the past month).
  • Patients 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 patients 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 patients 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 patients 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.
  • 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) <110 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 mL/min/1.73 m2 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 patient's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03236311


Locations
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United States, California
Investigational Site Number 8400003
Los Angeles, California, United States, 90048
United States, Florida
Investigational Site Number 8400001
Jacksonville, Florida, United States, 32209
Investigational Site Number 8400013
Wellington, Florida, United States, 33449
United States, Maryland
Investigational Site Number 8400008
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Investigational Site Number 8400006
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
Investigational Site Number 8400010
Philadelphia, Pennsylvania, United States, 19104
Denmark
Investigational Site Number 2080001
København Nv, Denmark, 2400
Korea, Republic of
Investigational Site Number 4100002
Seoul, Korea, Republic of, 03722
Netherlands
Investigational Site Number 5280001
Nijmegen, Netherlands, 6525 GA
Sweden
Investigational Site Number 7520001
Lund, Sweden, 221 85
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03236311     History of Changes
Other Study ID Numbers: ACT14656
2016-000629-38
U1111-1182-1709 ( Other Identifier: UTN )
First Posted: August 1, 2017    Key Record Dates
Last Update Posted: January 14, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Angina, Stable
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Adenosine
Regadenoson
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adenosine A2 Receptor Agonists