<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03236311</url>
  </required_header>
  <id_info>
    <org_study_id>ACT14656</org_study_id>
    <secondary_id>2016-000629-38</secondary_id>
    <secondary_id>U1111-1182-1709</secondary_id>
    <nct_id>NCT03236311</nct_id>
  </id_info>
  <brief_title>A Dose Titration Study to Assess the Effects of SAR407899 in Patients With MVA and/or Persistent Stable Angina Despite Angiographically Successful PCI</brief_title>
  <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 Percutaneous Coronary Intervention (PCI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow&#xD;
      reserve (CFR) in participants with microvascular angina (MVA) and/or persistent stable angina&#xD;
      despite angiographically successful percutaneous coronary intervention (PCI).&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire&#xD;
           physical limitation scale (SAQ-PL) in participants with MVA and/or persistent stable&#xD;
           angina despite angiographically successful PCI.&#xD;
&#xD;
        -  To assess the safety of SAR407899 in participants with MVA and/or persistent stable&#xD;
           angina despite angiographically successful PCI with a focus on identified risks such as&#xD;
           hypotension and orthostatic hypotension.&#xD;
&#xD;
        -  To assess SAR407899 plasma concentrations in MVA participants and/or persistent stable&#xD;
           angina despite angiographically successful PCI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The total duration of study per participant was:&#xD;
&#xD;
      - up to 9 weeks for participants with previous coronary artery angiography or coronary&#xD;
      computed tomography angiography (CCTA) within 24 months prior to screening with up to 4 weeks&#xD;
      screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up&#xD;
      after the last investigational medicinal product administration.&#xD;
&#xD;
      or&#xD;
&#xD;
      - up to 11 weeks for participants with previous coronary artery angiography or CCTA between&#xD;
      24 months and 5 years prior to screening who need CCTA during screening period with up to 6&#xD;
      weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week&#xD;
      follow-up after the last investigational medicinal product administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    (Recruitment was early terminated due to slow recruitment. Not linked to any safety concern.)&#xD;
  </why_stopped>
  <start_date type="Actual">October 12, 2017</start_date>
  <completion_date type="Actual">July 23, 2018</completion_date>
  <primary_completion_date type="Actual">July 23, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>Absolute change from baseline to Week 4 in uncorrected global CFR, as assessed by the central core laboratory. The global CFR is the ratio of absolute myocardial blood flow (MBF) at stress over that at rest. The MBF was assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Angina-induced Physical Limitation Assessed Using Seattle Angina Questionnaire Physical Limitation Scale (SAQ-PL) at Week 4</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>The SAQ-PL measures how common daily activities representing low, medium, and high exertional requirements were limited by angina (9 items). It was scored by assigning each response an ordinal value, beginning with 1 for the response that implied the 'lowest level of functioning' to 5 for 'not at all limited', and summing across the 9 items. The score of 9 items was then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range of the scale and multiplying by 100. The range of scores was 0 to 100, with higher scores indicates better functioning. A change of 10 points was considered to be clinically important.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Parameter: SAR407899 Plasma Concentration</measure>
    <time_frame>Day 1, 8, 15, 22, and Day 29</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Microvascular Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR407899</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAR407899</intervention_name>
    <description>Pharmaceutical form: Capsule Route of administration: Oral</description>
    <arm_group_label>SAR407899</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Pharmaceutical form: Capsule Route of administration: Oral</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adenosine</intervention_name>
    <description>Pharmaceutical form: Solution for injection Route of administration: Intravenous</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>SAR407899</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Regadenoson</intervention_name>
    <description>Pharmaceutical form: Solution for injection Route of administration: Intravenous</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>SAR407899</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>13N-ammonia</intervention_name>
    <description>Pharmaceutical form: Solution for injection Route of administration: Intravenous</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>SAR407899</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>82Rubidium</intervention_name>
    <description>Pharmaceutical form: Solution for injection Route of administration: Intravenous</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>SAR407899</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Male or female participants not at childbearing potential &gt;=18 year-old or legal age&#xD;
             of majority.&#xD;
&#xD;
          -  Female participant if she has undergone sterilization at least 3 months earlier or was&#xD;
             post-menopausal.&#xD;
&#xD;
          -  Post-menopausal status was defined by having no menses for 12 months without an&#xD;
             alternative medical cause.&#xD;
&#xD;
          -  In females not treated with hormonal replacement therapy (HRT), menopausal status was&#xD;
             confirmed by a high follicle stimulating hormone (FSH) level greater than 40&#xD;
             international units per litre (IU/L).&#xD;
&#xD;
          -  In females on HRT and whose menopausal status was in doubt (i.e. in women aged less&#xD;
             than 45 years), a highly effective contraception methods was required. Contraception&#xD;
             was used during the whole study and for at least seven days corresponding to time&#xD;
             needed to eliminate study treatment.&#xD;
&#xD;
          -  Symptomatic stable angina pectoris (typical or atypical symptoms with an average of at&#xD;
             least bi-weekly episodes over the past month).&#xD;
&#xD;
          -  Participants with non-obstructive (&lt;50% stenosis) coronary arteries or intermediate&#xD;
             stenosis (between 50 and 70%) should have fractional flow reserve (FFR) &gt;0.80 or&#xD;
             instantaneous wave-free ratio (iFR) &gt;0.89 on angiogram, documented within the previous&#xD;
             24 months*. In participants with stenting, a minimum diameter stenosis of &lt;10% is&#xD;
             required.&#xD;
&#xD;
        or Coronary computed tomography angiography (CCTA) with finding of non-obstructive coronary&#xD;
        arteries within the past 24 months* in participants without previous percutaneous coronary&#xD;
        intervention (PCI).&#xD;
&#xD;
        *Note: in cases of clinically suspected progression of atherosclerosis as per the&#xD;
        Investigator, a more contemporary (i.e., 6 months) evidence should be provided.&#xD;
&#xD;
        or CCTA performed during screening period, with finding of non-obstructive coronary&#xD;
        arteries, in participants diagnosed with microvascular angina (MVA) and stable angina&#xD;
        without previous PCI who did not have a coronary angiogram or CCTA in the previous 24&#xD;
        months but between 24 months to 5 years.&#xD;
&#xD;
        - Baseline global coronary flow reserve (CFR) (measured during the study) assessed by&#xD;
        13N-ammonia or 82Rubidium positron emission tomography (PET) scan &lt;2.0.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Any use of nitrates (except short-acting nitrates) and/or dipyridamole and/or&#xD;
             phosphodiesterase type 5 (PDE 5) inhibitors within one week prior to baseline PET scan&#xD;
             or anticipated to be used during the study.&#xD;
&#xD;
          -  Esophageal dysmotility or esophagitis.&#xD;
&#xD;
          -  Participants with acute coronary syndrome (ACS) (myocardial infarction [MI] and/or&#xD;
             unstable angina) in previous 3 months.&#xD;
&#xD;
          -  Unsuccessful or incomplete coronary revascularization with residual obstructive&#xD;
             stenosis or coronary artery disease (CAD) progression in native vessels as documented&#xD;
             on invasive coronary angiography (&gt;=50% stenosis) within 24 months of enrollment.&#xD;
&#xD;
          -  Percutaneous coronary intervention performed at the time of an ACS (MI or unstable&#xD;
             angina) in the previous 12 months.&#xD;
&#xD;
          -  Recent PCI within the past 3 months.&#xD;
&#xD;
          -  Participants with history of coronary artery bypass grafting (CABG).&#xD;
&#xD;
          -  Recent (&lt;=3 months) major surgery (i.e. valvular surgery, surgery for congenital heart&#xD;
             disease), stroke, transient ischemic attack [TIA], sustained ventricular arrhythmia,&#xD;
             clinically significant structural heart disease (moderate-severe valvular disease,&#xD;
             hypertrophic cardiomyopathy, congenital heart disease, pulmonary hypertension).&#xD;
&#xD;
          -  Regional local flow abnormal perfusion defects at baseline PET scan*.&#xD;
&#xD;
             *Note: if contemporary evidence with invasive coronary angiography or CCTA&#xD;
             demonstrates non-obstructive coronary arteries or if the regional local flow abnormal&#xD;
             perfusion defect on PET scan is consistent with previous studies then participant&#xD;
             qualifies for the study.&#xD;
&#xD;
          -  Participants with cardiac conduction abnormalities (second or third degree&#xD;
             atrioventricular [AV] block, sick sinus syndrome, symptomatic bradycardia, sinus node&#xD;
             disease) except in participants fitted with a functioning pacemaker.&#xD;
&#xD;
          -  History or known carotid stenosis:&#xD;
&#xD;
          -  Carotid stenosis (&gt;50%) or&#xD;
&#xD;
          -  History of carotid stenosis in participants with previous symptoms.&#xD;
&#xD;
          -  Contraindication or known hypersensitivity to adenosine or regadenoson.&#xD;
&#xD;
          -  Contraindication to aminophylline.&#xD;
&#xD;
          -  Contraindication to vasodilator stress PET scan and/or CCTA if CCTA needed during&#xD;
             screening.&#xD;
&#xD;
          -  Inability to discontinue treatment with methylxanthines treatment within 24 hours&#xD;
             prior to PET scan.&#xD;
&#xD;
          -  Participant unable to read, understand and fill a questionnaire without any help (eg,&#xD;
             partially visually impaired or blind).&#xD;
&#xD;
          -  Systolic blood pressure (SBP) &lt;110 millimeter of mercury (mmHg) at baseline.&#xD;
&#xD;
          -  Presence at baseline of symptomatic orthostatic hypotension (SBP decrease of 20 mmHg&#xD;
             or more at Minute 3 or Minute 5 between seated and standing position), or asymptomatic&#xD;
             orthostatic hypotension with a decrease in SBP equal or greater than 30 mmHg at Minute&#xD;
             3 or Minute 5 when changing from the seated to the standing position.&#xD;
&#xD;
          -  Renal impairment with estimated glomerular filtration rate (eGFR) &lt;50&#xD;
             milliliter/minute/1.73 square meter (mL/min/1.73 m^2) at screening and baseline.&#xD;
&#xD;
          -  Drug-induced liver injury related criteria:&#xD;
&#xD;
          -  Underlying hepatobiliary disease.&#xD;
&#xD;
          -  Alanine Aminotransferase (ALT) &gt;3 times the upper limit of normal (ULN).&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a&#xD;
        participant's potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number 8400003</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 8400001</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 8400013</name>
      <address>
        <city>Wellington</city>
        <state>Florida</state>
        <zip>33449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 8400008</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 8400006</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 8400010</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 2080001</name>
      <address>
        <city>København Nv</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100002</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 5280001</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 7520001</name>
      <address>
        <city>Lund</city>
        <zip>221 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Sweden</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <results_first_submitted>June 17, 2019</results_first_submitted>
  <results_first_submitted_qc>June 17, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 11, 2019</results_first_posted>
  <last_update_submitted>March 15, 2022</last_update_submitted>
  <last_update_submitted_qc>March 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Angina, Stable</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenosine</mesh_term>
    <mesh_term>Regadenoson</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03236311/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 3, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03236311/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted in United States, South Korea, Sweden, Netherlands and Denmark from 12 Oct 2017 to 23 Jul 2018.</recruitment_details>
      <pre_assignment_details>A total of 10 participants who met all of the inclusion criteria and none of the exclusion criteria were randomized and enrolled in the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Matching placebo for 4 weeks.</description>
        </group>
        <group group_id="P2">
          <title>SAR407899</title>
          <description>SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis was performed on Randomized population.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Matching placebo for 4 weeks.</description>
        </group>
        <group group_id="B2">
          <title>SAR407899</title>
          <description>SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.8" spread="9.3"/>
                    <measurement group_id="B2" value="57.2" spread="8.5"/>
                    <measurement group_id="B3" value="61.0" spread="9.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4</title>
        <description>Absolute change from baseline to Week 4 in uncorrected global CFR, as assessed by the central core laboratory. The global CFR is the ratio of absolute myocardial blood flow (MBF) at stress over that at rest. The MBF was assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <population>Analysis was performed on modified intent-to-treat (mITT) population that included all randomized participants analyzed according to the treatment group allocated by randomization; who received at least 1 dose or part of a dose of the investigational medicinal product (IMP) and with an evaluable primary efficacy endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Matching placebo for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>SAR407899</title>
            <description>SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4</title>
          <description>Absolute change from baseline to Week 4 in uncorrected global CFR, as assessed by the central core laboratory. The global CFR is the ratio of absolute myocardial blood flow (MBF) at stress over that at rest. The MBF was assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.</description>
          <population>Analysis was performed on modified intent-to-treat (mITT) population that included all randomized participants analyzed according to the treatment group allocated by randomization; who received at least 1 dose or part of a dose of the investigational medicinal product (IMP) and with an evaluable primary efficacy endpoint.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="0.6"/>
                    <measurement group_id="O2" value="0.2" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Angina-induced Physical Limitation Assessed Using Seattle Angina Questionnaire Physical Limitation Scale (SAQ-PL) at Week 4</title>
        <description>The SAQ-PL measures how common daily activities representing low, medium, and high exertional requirements were limited by angina (9 items). It was scored by assigning each response an ordinal value, beginning with 1 for the response that implied the 'lowest level of functioning' to 5 for 'not at all limited', and summing across the 9 items. The score of 9 items was then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range of the scale and multiplying by 100. The range of scores was 0 to 100, with higher scores indicates better functioning. A change of 10 points was considered to be clinically important.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <population>As the number of participants randomized fell well below target (10 vs. 78), hence no data was collected and no analysis was performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Matching placebo for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>SAR407899</title>
            <description>SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Angina-induced Physical Limitation Assessed Using Seattle Angina Questionnaire Physical Limitation Scale (SAQ-PL) at Week 4</title>
          <description>The SAQ-PL measures how common daily activities representing low, medium, and high exertional requirements were limited by angina (9 items). It was scored by assigning each response an ordinal value, beginning with 1 for the response that implied the 'lowest level of functioning' to 5 for 'not at all limited', and summing across the 9 items. The score of 9 items was then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range of the scale and multiplying by 100. The range of scores was 0 to 100, with higher scores indicates better functioning. A change of 10 points was considered to be clinically important.</description>
          <population>As the number of participants randomized fell well below target (10 vs. 78), hence no data was collected and no analysis was performed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Parameter: SAR407899 Plasma Concentration</title>
        <time_frame>Day 1, 8, 15, 22, and Day 29</time_frame>
        <population>As the number of participants randomized fell well below target (10 vs. 78), hence no data was collected and no analysis was performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Matching placebo for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>SAR407899</title>
            <description>SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Parameter: SAR407899 Plasma Concentration</title>
          <population>As the number of participants randomized fell well below target (10 vs. 78), hence no data was collected and no analysis was performed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit)</time_frame>
      <desc>Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Matching placebo for 4 weeks.</description>
        </group>
        <group group_id="E2">
          <title>SAR407899</title>
          <description>SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDra 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina Pectoris</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Lower</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Sports Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dizziness Postural</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis Allergic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was prematurely terminated due to small number of participants entering randomization.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Trial Transparency Team</name_or_title>
      <organization>Sanofi</organization>
      <phone>800-633-1610 ext 1#</phone>
      <email>Contact-US@sanofi.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03236311
org study id: ACT14656
secondary id: 2016-000629-38
secondary id: U1111-1182-1709
nct id: NCT03236311
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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 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 participants 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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4
time frame: Baseline, Week 4
description: Absolute change from baseline to Week 4 in uncorrected global CFR, as assessed by the central core laboratory. The global CFR is the ratio of absolute myocardial blood flow (MBF) at stress over that at rest. The MBF was assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.
measure: Change From Baseline in Angina-induced Physical Limitation Assessed Using Seattle Angina Questionnaire Physical Limitation Scale (SAQ-PL) at Week 4
time frame: Baseline, Week 4
description: The SAQ-PL measures how common daily activities representing low, medium, and high exertional requirements were limited by angina (9 items). It was scored by assigning each response an ordinal value, beginning with 1 for the response that implied the 'lowest level of functioning' to 5 for 'not at all limited', and summing across the 9 items. The score of 9 items was then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range of the scale and multiplying by 100. The range of scores was 0 to 100, with higher scores indicates better functioning. A change of 10 points was considered to be clinically important.
measure: Pharmacokinetic Parameter: SAR407899 Plasma Concentration
time frame: Day 1, 8, 15, 22, and Day 29
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo for 4 weeks.
arm group label: SAR407899
arm group type: Experimental
description: SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
intervention type: Drug
intervention name: SAR407899
description: Pharmaceutical form: Capsule Route of administration: Oral
arm group label: SAR407899
intervention type: Drug
intervention name: Placebo
description: Pharmaceutical form: Capsule Route of administration: Oral
arm group label: Placebo
intervention type: Drug
intervention name: Adenosine
description: Pharmaceutical form: Solution for injection Route of administration: Intravenous
arm group label: Placebo
arm group label: SAR407899
intervention type: Drug
intervention name: Regadenoson
description: Pharmaceutical form: Solution for injection Route of administration: Intravenous
arm group label: Placebo
arm group label: SAR407899
intervention type: Drug
intervention name: 13N-ammonia
description: Pharmaceutical form: Solution for injection Route of administration: Intravenous
arm group label: Placebo
arm group label: SAR407899
intervention type: Drug
intervention name: 82Rubidium
description: Pharmaceutical form: Solution for injection Route of administration: Intravenous
arm group label: Placebo
arm group label: SAR407899
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Korea, Republic of
country: Netherlands
country: Sweden
country: United States
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Angina, Stable
mesh term: Adenosine
mesh term: Regadenoson
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was prematurely terminated due to small number of participants entering randomization.
point of contact: 