<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/NCT04478266</url>
  </required_header>
  <id_info>
    <org_study_id>EFC15935</org_study_id>
    <secondary_id>2020-001824-33</secondary_id>
    <secondary_id>U1111-1233-0486</secondary_id>
    <nct_id>NCT04478266</nct_id>
  </id_info>
  <brief_title>Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer</brief_title>
  <acronym>AMEERA-5</acronym>
  <official_title>A Randomized, Multicenter, Double-blind Phase 3 Study of Amcenestrant (SAR439859) Plus Palbociclib Versus Letrozole Plus Palbociclib for the Treatment of Patients With ER (+), HER2 (-) Breast Cancer Who Have Not Received Prior Systemic Anti-cancer Treatment for Advanced Disease</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To determine whether Amcenestrant (SAR439859) in combination with palbociclib improves&#xD;
      progression free survival (PFS) when compared with letrozole in combination with palbociclib&#xD;
      in participants with estrogen receptor positive (ER+), human epidermal growth factor receptor&#xD;
      2 negative (HER2-) advanced breast cancer who have not received any prior systemic anticancer&#xD;
      therapies for advanced disease.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        -  To compare the overall survival in both treatment arms.&#xD;
&#xD;
        -  To evaluate the objective response rate in both treatment arms.&#xD;
&#xD;
        -  To evaluate the duration of response in both treatment arms.&#xD;
&#xD;
        -  To evaluate the clinical benefit rate in both treatment arms.&#xD;
&#xD;
        -  To evaluate progression-free survival on next line of therapy.&#xD;
&#xD;
        -  To evaluate the pharmacokinetics of amcenestrant, and palbociclib.&#xD;
&#xD;
        -  To evaluate health-related quality of life in both treatment arms.&#xD;
&#xD;
        -  To evaluate the time to first chemotherapy in both treatment arms.&#xD;
&#xD;
        -  To evaluate safety in both treatment arms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study duration per participant is approximately 59 months, which includes a 33- month&#xD;
      treatment period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was terminated based on the review by an independent data monitoring committee of the&#xD;
    prespecified interim analysis of the Phase 3 AMEERA-5 efficacy data. No new safety signals were&#xD;
    observed.&#xD;
  </why_stopped>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Actual">May 26, 2023</completion_date>
  <primary_completion_date type="Actual">June 28, 2022</primary_completion_date>
  <phase>Phase 3</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>Progression-free Survival (PFS)</measure>
    <time_frame>From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first (maximum exposure: 81 weeks)</time_frame>
    <description>PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From randomization to the death due to any cause or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
    <description>OS was defined as the interval (in months) from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant was known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-month Progression-free Survival (PFS) Rate</measure>
    <time_frame>Month 12</time_frame>
    <description>Percentage of participants who were disease progression-free at Month 12 after randomization were reported in this outcome measure. PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The PFS rate at Month 12 was estimated using the Kaplan-Meier method and provided an estimation of the percentage of participants who were disease progression-free at Month 12 after randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Objective Response</measure>
    <time_frame>From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum exposure: 81 weeks)</time_frame>
    <description>Objective response was defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by investigator. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;) 10 millimeters (mm). PR was defined as at least a 30%decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>From the date of first response of CR or PR until disease progression or death, or start of any anti-cancer therapy or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
    <description>DOR was defined as time (in months) from first documented evidence of CR or PR until disease progression determined by investigator as per RECIST 1.1, or start of any anti-cancer therapy, or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinical Benefit</measure>
    <time_frame>From randomization until disease progression, or death, or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
    <description>Clinical Benefit was defined as the percentage of participants having a confirmed CR, PR, or stable disease (SD) for at least 24 weeks determined by investigator as per RECIST 1.1, from date of randomization until disease progression, or death, or data cut-off date, or initiation of post treatment anti-cancer therapy, whichever occurs first. As per RECIST 1.1; CR was defined as disappearance of all target, non-target lesions &amp; normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival on Next Line of Therapy (PFS2)</measure>
    <time_frame>From randomization to date first documented disease progression on the next systemic anti-cancer therapy, or death due to any cause, or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
    <description>PFS2 was defined as the time interval (in months) from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator, or death due to any cause in the absence of documented PD on the next systemic anti-cancer therapy, whichever occurs first. PD was defined as at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Plasma Concentrations of Amcenestrant</measure>
    <time_frame>Cycle 1 Day 1: 3 hours (hr) post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose</time_frame>
    <description>Amcenestrant plasma concentrations at specified time points were reported. Data for this outcome measure was not planned to be collected and analyzed for Letrozole+Palbociclib arm as pre-specified in protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Plasma Concentrations of Palbociclib</measure>
    <time_frame>Cycle 1 Day 1: 3 hr post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose</time_frame>
    <description>Palbociclib plasma concentrations at specified time points were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores</measure>
    <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
    <description>EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy &amp; assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, &amp; Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) &amp; GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional &amp; GHS/QoL=higher level of functioning, &amp; higher score for symptoms scales=higher symptom burden. Least Square (LS) mean and Standard Error (SE) were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported in this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores</measure>
    <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
    <description>QLQ-BR23: disease-specific Health-related QOL assesses breast cancer impact &amp; side effects of treatment. EORTCQLQ- BR23 contains 23 items: multi-item scales &amp; single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) &amp; 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, &amp; upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0-100. Higher score for functional scales=better outcome; higher score for symptoms scales=higher symptom burden. LS mean &amp; SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value &amp; stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC QLQ-BR45) Domain Scores</measure>
    <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
    <description>EORTC QLQ-BR45: comprised of all 23 items from the QLQ-BR23 plus an additional 22 items assessing endocrine therapy symptoms (10 items), endocrine sexual symptoms (4 items), breast satisfaction (2 items), and skin mucosis symptoms (6 items). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from Mixed Model Repeated Measures (MMRM) model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain (endocrine therapy symptoms, endocrine sexual symptoms, breast satisfaction and skin mucosis symptoms) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score</measure>
    <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
    <description>EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for VAS was reported in this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value Score</measure>
    <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
    <description>EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) &amp; VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort &amp; anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, &amp; extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state &amp; lower score indicate worse health state. LS mean and SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for health utility index value score was reported in this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Chemotherapy</measure>
    <time_frame>From randomization to the start date of the first chemotherapy (maximum exposure duration: 81 weeks)</time_frame>
    <description>Time to chemotherapy was defined as the time interval (in months) from the date of randomization to the start date of the first chemotherapy after disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Hematological Abnormalities During the Treatment Period</measure>
    <time_frame>From first dose of study treatment up to 30 days after last dose of study treatment (maximum exposure: 81 weeks)</time_frame>
    <description>Hematological parameters assessed were anemia, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, platelet count decreased. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 5.0 (NCI-CTCAE v 5.0), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Liver Function Abnormalities of Grade 3 and 4 During the Treatment Period</measure>
    <time_frame>From first dose of study treatment up to 30 days after last dose of study treatment (maximum exposure: 81 weeks)</time_frame>
    <description>Liver Function parameters assessed were aspartate aminotransferase increased, alanine aminotransferase increased, alkaline phosphatase increased, total bilirubin increased, gamma-glutamyl transferase increased. Parameters were assessed as per the NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment. Participants with Grade 3 and 4 liver function abnormalities were reported in this outcome measure.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1068</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Amcenestrant with Letrozole-matching placebo Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in Amcenestrant with Letrozole-matching placebo Arm will be administered: Amcenestrant dose, once daily, continuously. Letrozole-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle. Goserelin once every 4 weeks in pre/peri menopausal women and men</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Letrozole with Amcenestrant matching placebo Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in Letrozole with Amcenestrant-matching placebo Arm will be administered: Letrozole dose, once daily, continuously. Amcenestrant-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle Goserelin once every 4 weeks in pre/peri menopausal women and men</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amcenestrant-matching placebo</intervention_name>
    <description>Pharmaceutical form: Tablets Route of Administration: Oral</description>
    <arm_group_label>Letrozole with Amcenestrant matching placebo Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAR439859</intervention_name>
    <description>Pharmaceutical form: Tablets Route of Administration: Oral</description>
    <arm_group_label>Amcenestrant with Letrozole-matching placebo Arm</arm_group_label>
    <other_name>Amcenestrant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib</intervention_name>
    <description>Pharmaceutical form: Capsules/Tablets Route of Administration: Oral</description>
    <arm_group_label>Amcenestrant with Letrozole-matching placebo Arm</arm_group_label>
    <arm_group_label>Letrozole with Amcenestrant matching placebo Arm</arm_group_label>
    <other_name>Ibrance</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>Pharmaceutical form: Capsules Route of Administration: Orally</description>
    <arm_group_label>Letrozole with Amcenestrant matching placebo Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Goserelin</intervention_name>
    <description>Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous</description>
    <arm_group_label>Amcenestrant with Letrozole-matching placebo Arm</arm_group_label>
    <arm_group_label>Letrozole with Amcenestrant matching placebo Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole-matching placebo</intervention_name>
    <description>Pharmaceutical form: Capsules Route of Administration: Orally</description>
    <arm_group_label>Amcenestrant with Letrozole-matching placebo Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Adult participants with loco-regional recurrent or metastatic disease not amenable to&#xD;
             curative treatment.&#xD;
&#xD;
          -  Confirmed diagnosis of ER+/HER2- breast cancer.&#xD;
&#xD;
          -  No prior systemic treatment for loco-regional recurrent or metastatic disease.&#xD;
&#xD;
          -  Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors&#xD;
             (RECIST) v.1.1 or non-measurable bone-only disease.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.&#xD;
&#xD;
          -  Participants should be willing to provide tumor tissue.&#xD;
&#xD;
          -  Capable of giving informed consent.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Known active brain metastases.&#xD;
&#xD;
          -  Prior neo (adjuvant) treatment with any selective estrogen receptor degrader (SERD).&#xD;
&#xD;
          -  Inadequate organ and marrow function.&#xD;
&#xD;
          -  Disease recurrence while on, or within 12 months of completion of (neo)adjuvant&#xD;
             endocrine therapy.&#xD;
&#xD;
          -  Pregnant, breastfeeding, or woman of childbearing potential unwilling to use&#xD;
             recommended contraception methods.&#xD;
&#xD;
          -  Male participants who disagree to follow contraception.&#xD;
&#xD;
          -  Participants with advanced, symptomatic visceral spread, that are at risk of&#xD;
             life-threatening complications in the short term.&#xD;
&#xD;
          -  Participants with significant concomitant illness.&#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 :8400075</name>
      <address>
        <city>Daphne</city>
        <state>Alabama</state>
        <zip>36526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400083</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400066</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400038</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400056</name>
      <address>
        <city>Los Alamitos</city>
        <state>California</state>
        <zip>90720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400029</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400025</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400059</name>
      <address>
        <city>Lakeland</city>
        <state>Florida</state>
        <zip>33805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400053</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400081</name>
      <address>
        <city>Palm Bay</city>
        <state>Florida</state>
        <zip>32901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400055</name>
      <address>
        <city>Athens</city>
        <state>Georgia</state>
        <zip>30607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400016</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400034</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400035</name>
      <address>
        <city>Thomasville</city>
        <state>Georgia</state>
        <zip>31792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400039</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400008</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400006</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400013</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205-2003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400028</name>
      <address>
        <city>Scarborough</city>
        <state>Maine</state>
        <zip>04074-9308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400017</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400076</name>
      <address>
        <city>Danvers</city>
        <state>Massachusetts</state>
        <zip>01923</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400077</name>
      <address>
        <city>Newton</city>
        <state>Massachusetts</state>
        <zip>02463</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400002</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400005</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400004</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400058</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400015</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901-1914</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400024</name>
      <address>
        <city>Paramus</city>
        <state>New Jersey</state>
        <zip>00000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400010</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400023</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794-8121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400009</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400067</name>
      <address>
        <city>Tigard</city>
        <state>Oregon</state>
        <zip>97223</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400001</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400073</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78745</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400072</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400070</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400080</name>
      <address>
        <city>Denton</city>
        <state>Texas</state>
        <zip>76021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400061</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400068</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400084</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400086</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400078</name>
      <address>
        <city>Waco</city>
        <state>Texas</state>
        <zip>76712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400082</name>
      <address>
        <city>Webster</city>
        <state>Texas</state>
        <zip>77598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400085</name>
      <address>
        <city>Blacksburg</city>
        <state>Virginia</state>
        <zip>24060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8400069</name>
      <address>
        <city>Winchester</city>
        <state>Virginia</state>
        <zip>22601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320001</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1012AAR</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320005</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1019ABS</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320008</name>
      <address>
        <city>Capital Federal</city>
        <state>Buenos Aires</state>
        <zip>C1417DTB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320006</name>
      <address>
        <city>Pergamino</city>
        <state>Buenos Aires</state>
        <zip>B2700CPM</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320010</name>
      <address>
        <city>Cordoba</city>
        <state>Córdoba</state>
        <zip>5000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320002</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>2000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320004</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1125ABD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320003</name>
      <address>
        <city>La Rioja</city>
        <zip>5300</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320009</name>
      <address>
        <city>Mar del Plata</city>
        <zip>B7600FYK</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320007</name>
      <address>
        <city>Salta</city>
        <zip>4400</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360004</name>
      <address>
        <city>Macquarie Park</city>
        <state>New South Wales</state>
        <zip>2109</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360005</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360003</name>
      <address>
        <city>Wahroonga</city>
        <state>New South Wales</state>
        <zip>2076</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360002</name>
      <address>
        <city>Richmond</city>
        <state>Victoria</state>
        <zip>3121</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360001</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0400001</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0560003</name>
      <address>
        <city>Bruxelles</city>
        <zip>BE-1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0560004</name>
      <address>
        <city>Charleroi</city>
        <zip>B-6000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0560001</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0560002</name>
      <address>
        <city>Namur</city>
        <zip>5000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0760005</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90035 003</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0760006</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>91350-250</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0760007</name>
      <address>
        <city>Sao Paulo</city>
        <state>São Paulo</state>
        <zip>01509-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0760003</name>
      <address>
        <city>Sao Paulo</city>
        <state>São Paulo</state>
        <zip>04014-002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0760004</name>
      <address>
        <city>Rio De Janeiro</city>
        <zip>20230-130</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0760008</name>
      <address>
        <city>São Paulo</city>
        <zip>04321-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000004</name>
      <address>
        <city>Burgas</city>
        <zip>8000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000005</name>
      <address>
        <city>Dobrich</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000008</name>
      <address>
        <city>Russe</city>
        <zip>7002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000001</name>
      <address>
        <city>Sofia</city>
        <zip>1797</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1240004</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 2V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1240002</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1240007</name>
      <address>
        <city>Greenfield Park</city>
        <state>Quebec</state>
        <zip>J4V 2H1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1240014</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1S6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1240005</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520005</name>
      <address>
        <city>La Serena</city>
        <state>Coquimbo</state>
        <zip>1720430</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520004</name>
      <address>
        <city>Temuco</city>
        <state>La Araucanía</state>
        <zip>4810561</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520009</name>
      <address>
        <city>Talca</city>
        <state>Maule</state>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520011</name>
      <address>
        <city>Santaigo</city>
        <state>Reg Metropolitana De Santiago</state>
        <zip>8241470</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520006</name>
      <address>
        <city>Santiago</city>
        <state>Reg Metropolitana De Santiago</state>
        <zip>7650568</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520002</name>
      <address>
        <city>Santiago</city>
        <state>Reg Metropolitana De Santiago</state>
        <zip>8420383</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520001</name>
      <address>
        <city>Viña del Mar</city>
        <state>Valparaíso</state>
        <zip>2520598</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520003</name>
      <address>
        <city>Santiago de Chile</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520007</name>
      <address>
        <city>Santiago</city>
        <zip>7500921</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560038</name>
      <address>
        <city>Baoding</city>
        <zip>071000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560008</name>
      <address>
        <city>Beijing</city>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560035</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560003</name>
      <address>
        <city>Changchun</city>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560036</name>
      <address>
        <city>Changchun</city>
        <zip>130041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560013</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560019</name>
      <address>
        <city>Chongqing</city>
        <zip>400030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560031</name>
      <address>
        <city>Dalian</city>
        <zip>116011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560021</name>
      <address>
        <city>Dalian</city>
        <zip>116027</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560054</name>
      <address>
        <city>Deyang</city>
        <zip>618000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560043</name>
      <address>
        <city>Fuzhou</city>
        <zip>354200</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560025</name>
      <address>
        <city>Guangzhou</city>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560006</name>
      <address>
        <city>Hangzhou</city>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560007</name>
      <address>
        <city>Hangzhou</city>
        <zip>310009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560002</name>
      <address>
        <city>Hangzhou</city>
        <zip>310016</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560005</name>
      <address>
        <city>Hangzhou</city>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560011</name>
      <address>
        <city>Harbin</city>
        <zip>150081</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560041</name>
      <address>
        <city>Hefei</city>
        <zip>233004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560018</name>
      <address>
        <city>Jinan</city>
        <zip>250013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560046</name>
      <address>
        <city>Jinan</city>
        <zip>250117</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560051</name>
      <address>
        <city>Jining</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560017</name>
      <address>
        <city>Linyi</city>
        <zip>276000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560055</name>
      <address>
        <city>Luoyang</city>
        <zip>471003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560048</name>
      <address>
        <city>Neijiang</city>
        <zip>641003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560001</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560037</name>
      <address>
        <city>Shaoguan</city>
        <zip>512025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560028</name>
      <address>
        <city>Tianjin</city>
        <zip>300060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560033</name>
      <address>
        <city>Wuhan</city>
        <zip>430060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560024</name>
      <address>
        <city>Wuhan</city>
        <zip>430079</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560045</name>
      <address>
        <city>Xi'an</city>
        <zip>710004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560044</name>
      <address>
        <city>Xi'An</city>
        <zip>710061</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560027</name>
      <address>
        <city>Xuzhou</city>
        <zip>221009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560049</name>
      <address>
        <city>Yantai</city>
        <zip>264000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1560022</name>
      <address>
        <city>Zhengzhou</city>
        <zip>450008</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2030001</name>
      <address>
        <city>Brno</city>
        <zip>65653</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2030002</name>
      <address>
        <city>Praha 2</city>
        <zip>12808</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2460001</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2460002</name>
      <address>
        <city>Tampere</city>
        <zip>33520</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2460003</name>
      <address>
        <city>Turku</city>
        <zip>FIN-20520</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500009</name>
      <address>
        <city>Nice</city>
        <zip>06189</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500003</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500001</name>
      <address>
        <city>Paris</city>
        <zip>75248</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500006</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500007</name>
      <address>
        <city>Saint Cloud</city>
        <zip>92210</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500002</name>
      <address>
        <city>Saint-Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500010</name>
      <address>
        <city>Strasbourg</city>
        <zip>67033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500005</name>
      <address>
        <city>TOULOUSE Cedex 9</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500004</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2680005</name>
      <address>
        <city>Batumi</city>
        <zip>6000</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2680006</name>
      <address>
        <city>Kutaisi</city>
        <zip>4600</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2680001</name>
      <address>
        <city>Tbilisi</city>
        <zip>0112</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2680002</name>
      <address>
        <city>Tbilisi</city>
        <zip>0144</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2680004</name>
      <address>
        <city>Tbilisi</city>
        <zip>0159</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2680007</name>
      <address>
        <city>Tbilisi</city>
        <zip>0159</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2680003</name>
      <address>
        <city>Tbilisi</city>
        <zip>0168</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2760006</name>
      <address>
        <city>Bottrop</city>
        <zip>46236</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2760003</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2760007</name>
      <address>
        <city>Oldenburg in Holstein</city>
        <zip>23758</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2760001</name>
      <address>
        <city>Ulm</city>
        <zip>89075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3480008</name>
      <address>
        <city>Budapest</city>
        <zip>1115</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3480011</name>
      <address>
        <city>Gyula</city>
        <zip>5700</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3480005</name>
      <address>
        <city>Győr</city>
        <zip>9023</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3480003</name>
      <address>
        <city>Kaposvár</city>
        <zip>7400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3480009</name>
      <address>
        <city>Kecskemét</city>
        <zip>6000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3480010</name>
      <address>
        <city>Miskolc</city>
        <zip>3526</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3480001</name>
      <address>
        <city>Nyíregyháza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800008</name>
      <address>
        <city>Meldola (FC)</city>
        <state>Emilia-Romagna</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800003</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800007</name>
      <address>
        <city>Monza</city>
        <state>Monza E Brianza</state>
        <zip>20052</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800010</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800004</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800002</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800006</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800005</name>
      <address>
        <city>Prato</city>
        <zip>59100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920016</name>
      <address>
        <city>Nagoya-shi</city>
        <state>Aichi</state>
        <zip>460-0001</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920007</name>
      <address>
        <city>Nagoya-shi</city>
        <state>Aichi</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920002</name>
      <address>
        <city>Kashiwa-shi</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920009</name>
      <address>
        <city>Matsuyama-shi</city>
        <state>Ehime</state>
        <zip>791-0280</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920019</name>
      <address>
        <city>Kurume-shi</city>
        <state>Fukuoka</state>
        <zip>830-0013</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920017</name>
      <address>
        <city>Takasaki-shi</city>
        <state>Gunma</state>
        <zip>370-0829</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920010</name>
      <address>
        <city>Hiroshima-shi</city>
        <state>Hiroshima</state>
        <zip>730-8518</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920001</name>
      <address>
        <city>Sapporo-shi</city>
        <state>Hokkaido</state>
        <zip>003-0804</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920012</name>
      <address>
        <city>Kagoshima-shi</city>
        <state>Kagoshima</state>
        <zip>892-0833</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920014</name>
      <address>
        <city>Yokohama-shi</city>
        <state>Kanagawa</state>
        <zip>222-0036</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920006</name>
      <address>
        <city>Yokohama-shi</city>
        <state>Kanagawa</state>
        <zip>241-8515</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920020</name>
      <address>
        <city>Sendai-shi</city>
        <state>Miyagi</state>
        <zip>980-0803</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920022</name>
      <address>
        <city>Miyazaki-shi</city>
        <state>Miyazaki</state>
        <zip>880-8510</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920008</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka</state>
        <zip>540-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920018</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka</state>
        <zip>553-0003</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920013</name>
      <address>
        <city>Hidaka-shi</city>
        <state>Saitama</state>
        <zip>350-1241</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920021</name>
      <address>
        <city>Shizuoka-shi</city>
        <state>Shizuoka</state>
        <zip>420-8527</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920003</name>
      <address>
        <city>Koto-ku</city>
        <state>Tokyo</state>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920015</name>
      <address>
        <city>Meguro-ku</city>
        <state>Tokyo</state>
        <zip>152-8902</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3920005</name>
      <address>
        <city>Shinagawa-ku</city>
        <state>Tokyo</state>
        <zip>142-8666</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100006</name>
      <address>
        <city>Goyang-si</city>
        <state>Gyeonggi-do</state>
        <zip>10408</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100005</name>
      <address>
        <city>Seongnam</city>
        <state>Gyeonggi-do</state>
        <zip>463-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100007</name>
      <address>
        <city>Seoul</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100004</name>
      <address>
        <city>Seoul</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100003</name>
      <address>
        <city>Seoul</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100002</name>
      <address>
        <city>Seoul</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100001</name>
      <address>
        <city>Seoul</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>138-878</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100009</name>
      <address>
        <city>Seochogu</city>
        <zip>6591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100008</name>
      <address>
        <city>Seongnam-si, Gyeonggi-do</city>
        <zip>13496</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :5280006</name>
      <address>
        <city>Arnhem</city>
        <zip>6815 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :5280005</name>
      <address>
        <city>Delft</city>
        <zip>2625 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :5280001</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6160002</name>
      <address>
        <city>Tomaszow Mazowiecki</city>
        <state>Lódzkie</state>
        <zip>97-200</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6160007</name>
      <address>
        <city>Poznan</city>
        <state>Wielkopolskie</state>
        <zip>61-866</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200005</name>
      <address>
        <city>Almada</city>
        <zip>2801-951</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200001</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200002</name>
      <address>
        <city>Porto</city>
        <zip>4200-319</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430007</name>
      <address>
        <city>Arkhangelsk</city>
        <zip>163045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430004</name>
      <address>
        <city>Krasnogorskiy District</city>
        <zip>143423</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430009</name>
      <address>
        <city>Moscow Region</city>
        <zip>143442</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430008</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430003</name>
      <address>
        <city>Moscow</city>
        <zip>117186</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430005</name>
      <address>
        <city>Moscow</city>
        <zip>117997</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430006</name>
      <address>
        <city>Moscow</city>
        <zip>129090</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430001</name>
      <address>
        <city>Saint -Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6430010</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>199034</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7020002</name>
      <address>
        <city>Singapore</city>
        <zip>119228</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7020004</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7020001</name>
      <address>
        <city>Singapore</city>
        <zip>329563</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7100004</name>
      <address>
        <city>Cape Town</city>
        <zip>7570</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7100006</name>
      <address>
        <city>Johannesburg</city>
        <zip>1709</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240011</name>
      <address>
        <city>Barcelona</city>
        <state>Barcelona [Barcelona]</state>
        <zip>08017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240008</name>
      <address>
        <city>Barcelona / Sabadell</city>
        <state>Castilla Y León</state>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240003</name>
      <address>
        <city>Santiago de Compostela</city>
        <state>Galicia [Galicia]</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240006</name>
      <address>
        <city>Madrid / Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240002</name>
      <address>
        <city>Madrid / Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240004</name>
      <address>
        <city>Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240005</name>
      <address>
        <city>Valencia</city>
        <state>Valenciana, Comunidad</state>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240001</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240007</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240009</name>
      <address>
        <city>Valencia</city>
        <zip>46015</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580007</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580002</name>
      <address>
        <city>Tainan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580001</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580003</name>
      <address>
        <city>Taipei</city>
        <zip>10449</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920006</name>
      <address>
        <city>Adana</city>
        <zip>01120</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920008</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920009</name>
      <address>
        <city>Ankara</city>
        <zip>06200</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920007</name>
      <address>
        <city>Antalya</city>
        <zip>07070</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920005</name>
      <address>
        <city>Bornova</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920013</name>
      <address>
        <city>Diyarbakır</city>
        <zip>21100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920003</name>
      <address>
        <city>Edirne</city>
        <zip>22030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920001</name>
      <address>
        <city>Istanbul</city>
        <zip>34214</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920011</name>
      <address>
        <city>Istanbul</city>
        <zip>34457</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920004</name>
      <address>
        <city>Istanbul</city>
        <zip>34722</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920012</name>
      <address>
        <city>İzmir</city>
        <zip>0000</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920010</name>
      <address>
        <city>Kocaeli</city>
        <zip>41380</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7920002</name>
      <address>
        <city>Malatya</city>
        <zip>44280</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040004</name>
      <address>
        <city>Kharkiv</city>
        <zip>61103</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040010</name>
      <address>
        <city>Kharkiv</city>
        <zip>61166</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040001</name>
      <address>
        <city>Kryvyi Rih</city>
        <zip>50048</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040002</name>
      <address>
        <city>Odesa</city>
        <zip>65025</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040007</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21029</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8260001</name>
      <address>
        <city>Glasgow</city>
        <state>Central Bedfordshire</state>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8260002</name>
      <address>
        <city>Edinburgh</city>
        <state>Edinburgh, City Of</state>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8260005</name>
      <address>
        <city>Blackburn</city>
        <state>Lancashire</state>
        <zip>BB2 3HH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>China</country>
    <country>Czechia</country>
    <country>Finland</country>
    <country>France</country>
    <country>Georgia</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Singapore</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Estonia</country>
    <country>Puerto Rico</country>
  </removed_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <results_first_submitted>June 13, 2023</results_first_submitted>
  <results_first_submitted_qc>June 13, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 6, 2023</results_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2023</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>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Palbociclib</mesh_term>
    <mesh_term>Goserelin</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>September 2, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT04478266/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>May 11, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT04478266/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 249 active sites in 30 countries. A total of 1277 participants were screened between 14 October 2020 and 11 November 2021, of which 209 were screen failures. Screen failures were mainly due to not meeting selection criteria.</recruitment_details>
      <pre_assignment_details>A total of 1068 participants were randomized, of which 2 participants were randomized but not exposed to study treatment. Randomization was stratified by De-novo metastatic disease (Yes or No); postmenopausal women (Yes or No); visceral metastasis defined by at least 1 liver, lung, brain metastasis, pleural, or peritoneal involvement (Yes or No). Results are based on primary completion date of 28 June 2022.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Letrozole + Palbociclib</title>
          <description>Participants received letrozole 2.5 milligram (mg) capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg orally (PO), once daily (QD) from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
        </group>
        <group group_id="P2">
          <title>Amcenestrant + Palbociclib</title>
          <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death, or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="534"/>
                <participants group_id="P2" count="534"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="533"/>
                <participants group_id="P2" count="533"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="534"/>
                <participants group_id="P2" count="534"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="99"/>
                <participants group_id="P2" count="118"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Poor compliance to protocol</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other: unspecified</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Randomized not treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing</title>
              <participants_list>
                <participants group_id="P1" count="397"/>
                <participants group_id="P2" count="377"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis was performed on safety population which included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention, analyzed according to the treatment arm they actually received.</population>
      <group_list>
        <group group_id="B1">
          <title>Letrozole + Palbociclib</title>
          <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg, PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
        </group>
        <group group_id="B2">
          <title>Amcenestrant + Palbociclib</title>
          <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</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="533"/>
            <count group_id="B2" value="533"/>
            <count group_id="B3" value="1066"/>
          </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="57.3" spread="12.3"/>
                    <measurement group_id="B2" value="57.8" spread="12.1"/>
                    <measurement group_id="B3" value="57.6" spread="12.2"/>
                  </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="529"/>
                    <measurement group_id="B2" value="524"/>
                    <measurement group_id="B3" value="1053"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="13"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="179"/>
                    <measurement group_id="B2" value="175"/>
                    <measurement group_id="B3" value="354"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="306"/>
                    <measurement group_id="B2" value="304"/>
                    <measurement group_id="B3" value="610"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
        <time_frame>From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on the ITT population which included all enrolled participants (i.e., who signed the informed consent form and for whom there was a confirmation of successful allocation of a randomization number by Interactive Response Technology [IRT].</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
          <population>Analysis was performed on the ITT population which included all enrolled participants (i.e., who signed the informed consent form and for whom there was a confirmation of successful allocation of a randomization number by Interactive Response Technology [IRT].</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="534"/>
                <count group_id="O2" value="534"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.6" lower_limit="14.1" upper_limit="NA">Upper limit of 95% confidence interval (CI) was not estimable due to the smaller number of participants with events.</measurement>
                    <measurement group_id="O2" value="14.1" lower_limit="13.9" upper_limit="NA">Upper limit of 95% confidence interval (CI) was not estimable due to the smaller number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A hierarchical testing procedure was used to ensure a strong control of the overall Type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at one-sided 2.5% for the primary and the first secondary outcome.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9304</p_value>
            <p_value_desc>One-sided p-value based on Stratified log-rank test. Threshold for statistical significance at 0.025 level.</p_value_desc>
            <method>Stratified Log-Rank test</method>
            <method_desc>Stratified on presence of De-novo metastatic disease, Postmenopausal women and Visceral metastasis according to IRT.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.209</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.939</ci_lower_limit>
            <ci_upper_limit>1.557</ci_upper_limit>
            <estimate_desc>Letrozole + Palbociclib versus Amcenestrant + Palbociclib</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS was defined as the interval (in months) from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant was known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.</description>
        <time_frame>From randomization to the death due to any cause or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS was defined as the interval (in months) from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant was known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.</description>
          <population>Analysis was performed on the ITT population.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="534"/>
                <count group_id="O2" value="534"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median, upper limit and lower limit of 95% CI were not estimable due to the smaller number of participants with events.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Median, upper limit and lower limit of 95% CI were not estimable due to the smaller number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>12-month Progression-free Survival (PFS) Rate</title>
        <description>Percentage of participants who were disease progression-free at Month 12 after randomization were reported in this outcome measure. PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The PFS rate at Month 12 was estimated using the Kaplan-Meier method and provided an estimation of the percentage of participants who were disease progression-free at Month 12 after randomization.</description>
        <time_frame>Month 12</time_frame>
        <population>Analysis was performed on the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>12-month Progression-free Survival (PFS) Rate</title>
          <description>Percentage of participants who were disease progression-free at Month 12 after randomization were reported in this outcome measure. PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The PFS rate at Month 12 was estimated using the Kaplan-Meier method and provided an estimation of the percentage of participants who were disease progression-free at Month 12 after randomization.</description>
          <population>Analysis was performed on the ITT population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="534"/>
                <count group_id="O2" value="534"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.2" lower_limit="61.2" upper_limit="74.2"/>
                    <measurement group_id="O2" value="65.5" lower_limit="59.1" upper_limit="71.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Objective Response</title>
        <description>Objective response was defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by investigator. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;) 10 millimeters (mm). PR was defined as at least a 30%decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.</description>
        <time_frame>From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Objective Response</title>
          <description>Objective response was defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by investigator. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;) 10 millimeters (mm). PR was defined as at least a 30%decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.</description>
          <population>Analysis was performed on the ITT population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="534"/>
                <count group_id="O2" value="534"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.3" lower_limit="38.1" upper_limit="46.6"/>
                    <measurement group_id="O2" value="32.2" lower_limit="28.3" upper_limit="36.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>DOR was defined as time (in months) from first documented evidence of CR or PR until disease progression determined by investigator as per RECIST 1.1, or start of any anti-cancer therapy, or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
        <time_frame>From the date of first response of CR or PR until disease progression or death, or start of any anti-cancer therapy or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on a subset of participants who had objective response.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>DOR was defined as time (in months) from first documented evidence of CR or PR until disease progression determined by investigator as per RECIST 1.1, or start of any anti-cancer therapy, or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
          <population>Analysis was performed on a subset of participants who had objective response.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="226"/>
                <count group_id="O2" value="172"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.0" lower_limit="11.1" upper_limit="NA">Upper limit of 95% CI was not estimable due to small number of progression events or death.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="11.4" upper_limit="NA">Median and upper limit of 95% CI was not estimable due to the small number of progression events or death.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Clinical Benefit</title>
        <description>Clinical Benefit was defined as the percentage of participants having a confirmed CR, PR, or stable disease (SD) for at least 24 weeks determined by investigator as per RECIST 1.1, from date of randomization until disease progression, or death, or data cut-off date, or initiation of post treatment anti-cancer therapy, whichever occurs first. As per RECIST 1.1; CR was defined as disappearance of all target, non-target lesions &amp; normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.</description>
        <time_frame>From randomization until disease progression, or death, or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Clinical Benefit</title>
          <description>Clinical Benefit was defined as the percentage of participants having a confirmed CR, PR, or stable disease (SD) for at least 24 weeks determined by investigator as per RECIST 1.1, from date of randomization until disease progression, or death, or data cut-off date, or initiation of post treatment anti-cancer therapy, whichever occurs first. As per RECIST 1.1; CR was defined as disappearance of all target, non-target lesions &amp; normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.</description>
          <population>Analysis was performed on the ITT population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="534"/>
                <count group_id="O2" value="534"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.4" lower_limit="78.9" upper_limit="85.5"/>
                    <measurement group_id="O2" value="76.0" lower_limit="72.2" upper_limit="79.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival on Next Line of Therapy (PFS2)</title>
        <description>PFS2 was defined as the time interval (in months) from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator, or death due to any cause in the absence of documented PD on the next systemic anti-cancer therapy, whichever occurs first. PD was defined as at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
        <time_frame>From randomization to date first documented disease progression on the next systemic anti-cancer therapy, or death due to any cause, or data cut-off date, whichever comes first (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival on Next Line of Therapy (PFS2)</title>
          <description>PFS2 was defined as the time interval (in months) from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator, or death due to any cause in the absence of documented PD on the next systemic anti-cancer therapy, whichever occurs first. PD was defined as at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.</description>
          <population>Analysis was performed on the ITT population.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="534"/>
                <count group_id="O2" value="534"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median, upper and lower limit of 95% CI was not estimable due to the smaller number of participants with events.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Median, upper and lower limit of 95% CI was not estimable due to the smaller number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics: Plasma Concentrations of Amcenestrant</title>
        <description>Amcenestrant plasma concentrations at specified time points were reported. Data for this outcome measure was not planned to be collected and analyzed for Letrozole+Palbociclib arm as pre-specified in protocol.</description>
        <time_frame>Cycle 1 Day 1: 3 hours (hr) post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose</time_frame>
        <population>Analysis was performed on the Pharmacokinetic-evaluable (amcenestrant) population that included all participants who took at least 1 dose of study intervention, and with at least one evaluable plasma concentration of amcenestrant post-treatment. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'Number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics: Plasma Concentrations of Amcenestrant</title>
          <description>Amcenestrant plasma concentrations at specified time points were reported. Data for this outcome measure was not planned to be collected and analyzed for Letrozole+Palbociclib arm as pre-specified in protocol.</description>
          <population>Analysis was performed on the Pharmacokinetic-evaluable (amcenestrant) population that included all participants who took at least 1 dose of study intervention, and with at least one evaluable plasma concentration of amcenestrant post-treatment. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'Number analyzed' = participants with available data for each specified category.</population>
          <units>nanograms per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="531"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1: 3 hr post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="473"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2890.0" spread="1783.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="283"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="399.5" spread="575.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="255"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="387.5" spread="685.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1: 3 hr post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="441"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2729.3" spread="1604.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 15: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="253"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="361.3" spread="572.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="215"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="303.4" spread="315.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="169"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="349.3" spread="385.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 7 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="162"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="337.5" spread="432.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 10 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="310.9" spread="253.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics: Plasma Concentrations of Palbociclib</title>
        <description>Palbociclib plasma concentrations at specified time points were reported.</description>
        <time_frame>Cycle 1 Day 1: 3 hr post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose</time_frame>
        <population>Analysis was performed on the Pharmacokinetic-evaluable (palbociclib) population that included all participants who took at least 1 dose of study intervention, and with at least one evaluable plasma concentration of palbociclib post-treatment. Here, 'Number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics: Plasma Concentrations of Palbociclib</title>
          <description>Palbociclib plasma concentrations at specified time points were reported.</description>
          <population>Analysis was performed on the Pharmacokinetic-evaluable (palbociclib) population that included all participants who took at least 1 dose of study intervention, and with at least one evaluable plasma concentration of palbociclib post-treatment. Here, 'Number analyzed' = participants with available data for each specified category.</population>
          <units>nanograms per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="532"/>
                <count group_id="O2" value="532"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1: 3 hr post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="479"/>
                    <count group_id="O2" value="472"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.265" spread="31.110"/>
                    <measurement group_id="O2" value="37.780" spread="31.005"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="264"/>
                    <count group_id="O2" value="274"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.541" spread="38.671"/>
                    <measurement group_id="O2" value="45.903" spread="20.086"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="201"/>
                    <count group_id="O2" value="227"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.409" spread="8.498"/>
                    <measurement group_id="O2" value="2.159" spread="7.368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1: 3 hr post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="316"/>
                    <count group_id="O2" value="385"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.234" spread="26.967"/>
                    <measurement group_id="O2" value="27.144" spread="24.667"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 15: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="237"/>
                    <count group_id="O2" value="247"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.176" spread="35.210"/>
                    <measurement group_id="O2" value="42.882" spread="18.081"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="183"/>
                    <count group_id="O2" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.301" spread="11.796"/>
                    <measurement group_id="O2" value="1.615" spread="4.283"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="131"/>
                    <count group_id="O2" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.767" spread="17.787"/>
                    <measurement group_id="O2" value="1.390" spread="3.052"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 7 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="143"/>
                    <count group_id="O2" value="142"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.716" spread="2.058"/>
                    <measurement group_id="O2" value="1.461" spread="1.722"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 10 Day 1: pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.793" spread="7.675"/>
                    <measurement group_id="O2" value="1.489" spread="1.155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores</title>
        <description>EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy &amp; assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, &amp; Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) &amp; GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional &amp; GHS/QoL=higher level of functioning, &amp; higher score for symptoms scales=higher symptom burden. Least Square (LS) mean and Standard Error (SE) were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported in this outcome measure.</description>
        <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
        <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores</title>
          <description>EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy &amp; assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, &amp; Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) &amp; GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional &amp; GHS/QoL=higher level of functioning, &amp; higher score for symptoms scales=higher symptom burden. Least Square (LS) mean and Standard Error (SE) were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported in this outcome measure.</description>
          <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="533"/>
                <count group_id="O2" value="533"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>GHS/QoL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="491"/>
                    <count group_id="O2" value="485"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="0.6"/>
                    <measurement group_id="O2" value="3.1" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="488"/>
                    <count group_id="O2" value="484"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="0.5"/>
                    <measurement group_id="O2" value="2.6" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="490"/>
                    <count group_id="O2" value="482"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="0.7"/>
                    <measurement group_id="O2" value="2.0" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="490"/>
                    <count group_id="O2" value="484"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="0.6"/>
                    <measurement group_id="O2" value="4.1" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="491"/>
                    <count group_id="O2" value="485"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="0.6"/>
                    <measurement group_id="O2" value="-1.2" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="489"/>
                    <count group_id="O2" value="485"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" spread="0.7"/>
                    <measurement group_id="O2" value="4.4" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="490"/>
                    <count group_id="O2" value="484"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="0.7"/>
                    <measurement group_id="O2" value="-2.0" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea and vomiting</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="485"/>
                    <count group_id="O2" value="478"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="0.4"/>
                    <measurement group_id="O2" value="-0.6" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="491"/>
                    <count group_id="O2" value="485"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.8" spread="0.7"/>
                    <measurement group_id="O2" value="-6.8" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnea</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="488"/>
                    <count group_id="O2" value="480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1" spread="0.7"/>
                    <measurement group_id="O2" value="-0.7" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="490"/>
                    <count group_id="O2" value="483"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.9" spread="0.9"/>
                    <measurement group_id="O2" value="-3.9" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite loss</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="485"/>
                    <count group_id="O2" value="478"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="0.7"/>
                    <measurement group_id="O2" value="-2.7" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="486"/>
                    <count group_id="O2" value="477"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.8"/>
                    <measurement group_id="O2" value="0.0" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="490"/>
                    <count group_id="O2" value="480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.4"/>
                    <measurement group_id="O2" value="0.4" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Financial difficulties</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="488"/>
                    <count group_id="O2" value="485"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.1" spread="0.8"/>
                    <measurement group_id="O2" value="-4.0" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores</title>
        <description>QLQ-BR23: disease-specific Health-related QOL assesses breast cancer impact &amp; side effects of treatment. EORTCQLQ- BR23 contains 23 items: multi-item scales &amp; single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) &amp; 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, &amp; upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0-100. Higher score for functional scales=better outcome; higher score for symptoms scales=higher symptom burden. LS mean &amp; SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value &amp; stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported.</description>
        <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
        <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores</title>
          <description>QLQ-BR23: disease-specific Health-related QOL assesses breast cancer impact &amp; side effects of treatment. EORTCQLQ- BR23 contains 23 items: multi-item scales &amp; single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) &amp; 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, &amp; upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0-100. Higher score for functional scales=better outcome; higher score for symptoms scales=higher symptom burden. LS mean &amp; SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value &amp; stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported.</description>
          <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="533"/>
                <count group_id="O2" value="533"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Body image</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="463"/>
                    <count group_id="O2" value="464"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="0.7"/>
                    <measurement group_id="O2" value="1.1" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sexual functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="451"/>
                    <count group_id="O2" value="450"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" spread="0.6"/>
                    <measurement group_id="O2" value="-1.5" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sexual enjoyment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.4" spread="1.9"/>
                    <measurement group_id="O2" value="-8.7" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Future perspective</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="467"/>
                    <count group_id="O2" value="465"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="1.0"/>
                    <measurement group_id="O2" value="10.8" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systemic therapy side effects</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="466"/>
                    <count group_id="O2" value="466"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="0.5"/>
                    <measurement group_id="O2" value="3.7" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Breast symptoms</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="466"/>
                    <count group_id="O2" value="465"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.6" spread="0.5"/>
                    <measurement group_id="O2" value="-7.0" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Arm symptoms</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="466"/>
                    <count group_id="O2" value="466"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="0.6"/>
                    <measurement group_id="O2" value="-1.8" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Upset by hair loss</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.7" spread="2.2"/>
                    <measurement group_id="O2" value="-0.2" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC QLQ-BR45) Domain Scores</title>
        <description>EORTC QLQ-BR45: comprised of all 23 items from the QLQ-BR23 plus an additional 22 items assessing endocrine therapy symptoms (10 items), endocrine sexual symptoms (4 items), breast satisfaction (2 items), and skin mucosis symptoms (6 items). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from Mixed Model Repeated Measures (MMRM) model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain (endocrine therapy symptoms, endocrine sexual symptoms, breast satisfaction and skin mucosis symptoms) was reported.</description>
        <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
        <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC QLQ-BR45) Domain Scores</title>
          <description>EORTC QLQ-BR45: comprised of all 23 items from the QLQ-BR23 plus an additional 22 items assessing endocrine therapy symptoms (10 items), endocrine sexual symptoms (4 items), breast satisfaction (2 items), and skin mucosis symptoms (6 items). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from Mixed Model Repeated Measures (MMRM) model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain (endocrine therapy symptoms, endocrine sexual symptoms, breast satisfaction and skin mucosis symptoms) was reported.</description>
          <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="533"/>
                <count group_id="O2" value="533"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Breast Satisfaction</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="378"/>
                    <count group_id="O2" value="369"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="1.2"/>
                    <measurement group_id="O2" value="1.0" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Endocrine Sexual Symptoms</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="428"/>
                    <count group_id="O2" value="419"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="0.8"/>
                    <measurement group_id="O2" value="2.3" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Endocrine Therapy Symptoms</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="437"/>
                    <count group_id="O2" value="434"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="0.6"/>
                    <measurement group_id="O2" value="1.2" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin Mucosis Symptoms</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="438"/>
                    <count group_id="O2" value="434"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" spread="0.5"/>
                    <measurement group_id="O2" value="2.5" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score</title>
        <description>EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for VAS was reported in this outcome measure.</description>
        <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
        <population>Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle and were followed until disease progression, death or study cut-off date, whichever comes first (maximum exposure duration: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score</title>
          <description>EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for VAS was reported in this outcome measure.</description>
          <population>Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="492"/>
                <count group_id="O2" value="489"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" spread="0.5"/>
                    <measurement group_id="O2" value="3.8" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value Score</title>
        <description>EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) &amp; VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort &amp; anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, &amp; extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state &amp; lower score indicate worse health state. LS mean and SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for health utility index value score was reported in this outcome measure.</description>
        <time_frame>Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])</time_frame>
        <population>Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value Score</title>
          <description>EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) &amp; VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort &amp; anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, &amp; extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state &amp; lower score indicate worse health state. LS mean and SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for health utility index value score was reported in this outcome measure.</description>
          <population>Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="492"/>
                <count group_id="O2" value="489"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                    <measurement group_id="O2" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Chemotherapy</title>
        <description>Time to chemotherapy was defined as the time interval (in months) from the date of randomization to the start date of the first chemotherapy after disease progression.</description>
        <time_frame>From randomization to the start date of the first chemotherapy (maximum exposure duration: 81 weeks)</time_frame>
        <population>Analysis was performed on the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Chemotherapy</title>
          <description>Time to chemotherapy was defined as the time interval (in months) from the date of randomization to the start date of the first chemotherapy after disease progression.</description>
          <population>Analysis was performed on the ITT population.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="534"/>
                <count group_id="O2" value="534"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median, upper limit and lower limit of 95% CI was not estimable due to lower number of participants with events.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Median, upper limit and lower limit of 95% CI was not estimable due to lower number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Hematological Abnormalities During the Treatment Period</title>
        <description>Hematological parameters assessed were anemia, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, platelet count decreased. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 5.0 (NCI-CTCAE v 5.0), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment.</description>
        <time_frame>From first dose of study treatment up to 30 days after last dose of study treatment (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Hematological Abnormalities During the Treatment Period</title>
          <description>Hematological parameters assessed were anemia, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, platelet count decreased. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 5.0 (NCI-CTCAE v 5.0), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment.</description>
          <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="533"/>
                <count group_id="O2" value="533"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anemia: Grade 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="309"/>
                    <measurement group_id="O2" value="302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia: Grade 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108"/>
                    <measurement group_id="O2" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased: Grade 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98"/>
                    <measurement group_id="O2" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased: Grade 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="138"/>
                    <measurement group_id="O2" value="124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased: Grade 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased: Grade 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="150"/>
                    <measurement group_id="O2" value="217"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="277"/>
                    <measurement group_id="O2" value="199"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cell decreased: Grade 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="532"/>
                    <count group_id="O2" value="531"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81"/>
                    <measurement group_id="O2" value="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cell decreased: Grade 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="532"/>
                    <count group_id="O2" value="531"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="279"/>
                    <measurement group_id="O2" value="267"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cell decreased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="532"/>
                    <count group_id="O2" value="531"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="163"/>
                    <measurement group_id="O2" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cell decreased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="532"/>
                    <count group_id="O2" value="531"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased: Grade 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="285"/>
                    <measurement group_id="O2" value="220"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased: Grade 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Liver Function Abnormalities of Grade 3 and 4 During the Treatment Period</title>
        <description>Liver Function parameters assessed were aspartate aminotransferase increased, alanine aminotransferase increased, alkaline phosphatase increased, total bilirubin increased, gamma-glutamyl transferase increased. Parameters were assessed as per the NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment. Participants with Grade 3 and 4 liver function abnormalities were reported in this outcome measure.</description>
        <time_frame>From first dose of study treatment up to 30 days after last dose of study treatment (maximum exposure: 81 weeks)</time_frame>
        <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Letrozole + Palbociclib</title>
            <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
          <group group_id="O2">
            <title>Amcenestrant + Palbociclib</title>
            <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Liver Function Abnormalities of Grade 3 and 4 During the Treatment Period</title>
          <description>Liver Function parameters assessed were aspartate aminotransferase increased, alanine aminotransferase increased, alkaline phosphatase increased, total bilirubin increased, gamma-glutamyl transferase increased. Parameters were assessed as per the NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment. Participants with Grade 3 and 4 liver function abnormalities were reported in this outcome measure.</description>
          <population>Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="533"/>
                <count group_id="O2" value="533"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Aspartate aminotransferase increased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate aminotransferase increased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine aminotransferase increased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine aminotransferase increased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline phosphatase increased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="532"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline phosphatase increased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="532"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total bilirubin increased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total bilirubin increased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gamma-GT increased: Grade 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gamma-GT increased: Grade 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="533"/>
                    <count group_id="O2" value="532"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events (AE) data was collected from Baseline up to 30 days after last dose of study treatment (maximum exposure duration: 81 weeks), deaths were collected from baseline up to the cut-off date (28 June 2022)</time_frame>
      <desc>Reported AEs were assessed for safety population. All-Cause Mortality data collected during study was assessed for all randomized participants. Disease progression related death were not reported as AE.</desc>
      <group_list>
        <group group_id="E1">
          <title>Letrozole + Palbociclib</title>
          <description>Participants received letrozole 2.5 mg capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg, PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
        </group>
        <group group_id="E2">
          <title>Amcenestrant + Palbociclib</title>
          <description>Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 81 weeks).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 25.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="534"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="534"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="533"/>
                <counts group_id="E2" subjects_affected="63" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Anaemia Of Malignant Disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Left Ventricular Failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Acute Myocardial Infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Atrioventricular Block Complete</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Cardiac Failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Lower</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Intestinal Obstruction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Lower Gastrointestinal Haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Upper Gastrointestinal Haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Disease Progression</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile Duct Stone</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hepatic Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hepatic Function Abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hepatotoxicity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Bronchitis Bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Covid-19</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Covid-19 Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Device Related Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Focal Peritonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Neutropenic Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Paracancerous Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Procedural Complication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Stoma Complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Subdural Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Tibia Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Blood Follicle Stimulating Hormone Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Flank Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pathological Fracture</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Spinal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenocarcinoma Of Colon</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Cancer Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Colon Cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Diffuse Large B-Cell Lymphoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Gallbladder Cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Rectal Adenocarcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral Infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Cerebrovascular Accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Ischaemic Stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Psychomotor Hyperactivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Psychotic Disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Schizophrenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pyelocaliectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian Cyst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hydrothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Interstitial Lung Disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pulmonary Embolism</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pulmonary Oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep Vein Thrombosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="533"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="533"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Vena Cava Thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="533"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 25.0</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="428" subjects_at_risk="533"/>
                <counts group_id="E2" subjects_affected="396" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="437" subjects_affected="188" subjects_at_risk="533"/>
                <counts group_id="E2" events="188" subjects_affected="104" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" events="28" subjects_affected="27" subjects_at_risk="533"/>
                <counts group_id="E2" events="21" subjects_affected="21" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="79" subjects_affected="65" subjects_at_risk="533"/>
                <counts group_id="E2" events="69" subjects_affected="65" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="98" subjects_affected="71" subjects_at_risk="533"/>
                <counts group_id="E2" events="60" subjects_affected="53" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="99" subjects_affected="87" subjects_at_risk="533"/>
                <counts group_id="E2" events="85" subjects_affected="74" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="115" subjects_affected="86" subjects_at_risk="533"/>
                <counts group_id="E2" events="80" subjects_affected="60" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="54" subjects_affected="46" subjects_at_risk="533"/>
                <counts group_id="E2" events="43" subjects_affected="35" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="47" subjects_affected="42" subjects_at_risk="533"/>
                <counts group_id="E2" events="48" subjects_affected="42" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="92" subjects_affected="90" subjects_at_risk="533"/>
                <counts group_id="E2" events="96" subjects_affected="86" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Covid-19</sub_title>
                <counts group_id="E1" events="39" subjects_affected="39" subjects_at_risk="533"/>
                <counts group_id="E2" events="39" subjects_affected="39" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="35" subjects_affected="27" subjects_at_risk="533"/>
                <counts group_id="E2" events="46" subjects_affected="32" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="17" subjects_affected="15" subjects_at_risk="533"/>
                <counts group_id="E2" events="43" subjects_affected="38" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" events="210" subjects_affected="104" subjects_at_risk="533"/>
                <counts group_id="E2" events="106" subjects_affected="67" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Decreased</sub_title>
                <counts group_id="E1" events="64" subjects_affected="31" subjects_at_risk="533"/>
                <counts group_id="E2" events="16" subjects_affected="16" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" events="43" subjects_affected="39" subjects_at_risk="533"/>
                <counts group_id="E2" events="40" subjects_affected="36" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="109" subjects_affected="91" subjects_at_risk="533"/>
                <counts group_id="E2" events="115" subjects_affected="98" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="47" subjects_affected="40" subjects_at_risk="533"/>
                <counts group_id="E2" events="38" subjects_affected="35" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" events="20" subjects_affected="18" subjects_at_risk="533"/>
                <counts group_id="E2" events="46" subjects_affected="39" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="35" subjects_affected="30" subjects_at_risk="533"/>
                <counts group_id="E2" events="30" subjects_affected="24" subjects_at_risk="533"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="70" subjects_affected="58" subjects_at_risk="533"/>
                <counts group_id="E2" events="66" subjects_affected="52" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="31" subjects_affected="30" subjects_at_risk="533"/>
                <counts group_id="E2" events="43" subjects_affected="37" subjects_at_risk="533"/>
              </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="32" subjects_affected="30" subjects_at_risk="533"/>
                <counts group_id="E2" events="29" subjects_affected="27" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="65" subjects_affected="65" subjects_at_risk="533"/>
                <counts group_id="E2" events="41" subjects_affected="40" subjects_at_risk="533"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot Flush</sub_title>
                <counts group_id="E1" events="78" subjects_affected="78" subjects_at_risk="533"/>
                <counts group_id="E2" events="87" subjects_affected="84" subjects_at_risk="533"/>
              </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 terminated based on the review by an independent data monitoring committee of the prespecified interim analysis of the Phase 3 AMEERA-5 efficacy data.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Trial Transparency Team</name_or_title>
      <organization>Sanofi aventis recherche &amp; développement</organization>
      <phone>800-633-1610 ext 6#</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/NCT04478266
org study id: EFC15935
secondary id: 2020-001824-33
secondary id: U1111-1233-0486
nct id: NCT04478266
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Primary Objective:

      To determine whether Amcenestrant (SAR439859) in combination with palbociclib improves
      progression free survival (PFS) when compared with letrozole in combination with palbociclib
      in participants with estrogen receptor positive (ER+), human epidermal growth factor receptor
      2 negative (HER2-) advanced breast cancer who have not received any prior systemic anticancer
      therapies for advanced disease.

      Secondary Objective:

        -  To compare the overall survival in both treatment arms.

        -  To evaluate the objective response rate in both treatment arms.

        -  To evaluate the duration of response in both treatment arms.

        -  To evaluate the clinical benefit rate in both treatment arms.

        -  To evaluate progression-free survival on next line of therapy.

        -  To evaluate the pharmacokinetics of amcenestrant, and palbociclib.

        -  To evaluate health-related quality of life in both treatment arms.

        -  To evaluate the time to first chemotherapy in both treatment arms.

        -  To evaluate safety in both treatment arms.
Study duration per participant is approximately 59 months, which includes a 33- month
      treatment period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Progression-free Survival (PFS)
time frame: From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first (maximum exposure: 81 weeks)
description: PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
measure: Overall Survival (OS)
time frame: From randomization to the death due to any cause or data cut-off date, whichever comes first (maximum exposure: 81 weeks)
description: OS was defined as the interval (in months) from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant was known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.
measure: 12-month Progression-free Survival (PFS) Rate
time frame: Month 12
description: Percentage of participants who were disease progression-free at Month 12 after randomization were reported in this outcome measure. PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The PFS rate at Month 12 was estimated using the Kaplan-Meier method and provided an estimation of the percentage of participants who were disease progression-free at Month 12 after randomization.
measure: Percentage of Participants With Objective Response
time frame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum exposure: 81 weeks)
description: Objective response was defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by investigator. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30%decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
measure: Duration of Response (DOR)
time frame: From the date of first response of CR or PR until disease progression or death, or start of any anti-cancer therapy or data cut-off date, whichever comes first (maximum exposure: 81 weeks)
description: DOR was defined as time (in months) from first documented evidence of CR or PR until disease progression determined by investigator as per RECIST 1.1, or start of any anti-cancer therapy, or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
measure: Percentage of Participants With Clinical Benefit
time frame: From randomization until disease progression, or death, or data cut-off date, whichever comes first (maximum exposure: 81 weeks)
description: Clinical Benefit was defined as the percentage of participants having a confirmed CR, PR, or stable disease (SD) for at least 24 weeks determined by investigator as per RECIST 1.1, from date of randomization until disease progression, or death, or data cut-off date, or initiation of post treatment anti-cancer therapy, whichever occurs first. As per RECIST 1.1; CR was defined as disappearance of all target, non-target lesions & normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
measure: Progression-free Survival on Next Line of Therapy (PFS2)
time frame: From randomization to date first documented disease progression on the next systemic anti-cancer therapy, or death due to any cause, or data cut-off date, whichever comes first (maximum exposure: 81 weeks)
description: PFS2 was defined as the time interval (in months) from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator, or death due to any cause in the absence of documented PD on the next systemic anti-cancer therapy, whichever occurs first. PD was defined as at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
measure: Pharmacokinetics: Plasma Concentrations of Amcenestrant
time frame: Cycle 1 Day 1: 3 hours (hr) post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose
description: Amcenestrant plasma concentrations at specified time points were reported. Data for this outcome measure was not planned to be collected and analyzed for Letrozole+Palbociclib arm as pre-specified in protocol.
measure: Pharmacokinetics: Plasma Concentrations of Palbociclib
time frame: Cycle 1 Day 1: 3 hr post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose
description: Palbociclib plasma concentrations at specified time points were reported.
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores
time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
description: EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy & assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, & Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) & GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional & GHS/QoL=higher level of functioning, & higher score for symptoms scales=higher symptom burden. Least Square (LS) mean and Standard Error (SE) were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported in this outcome measure.
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores
time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
description: QLQ-BR23: disease-specific Health-related QOL assesses breast cancer impact & side effects of treatment. EORTCQLQ- BR23 contains 23 items: multi-item scales & single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) & 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, & upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0-100. Higher score for functional scales=better outcome; higher score for symptoms scales=higher symptom burden. LS mean & SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value & stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported.
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC QLQ-BR45) Domain Scores
time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
description: EORTC QLQ-BR45: comprised of all 23 items from the QLQ-BR23 plus an additional 22 items assessing endocrine therapy symptoms (10 items), endocrine sexual symptoms (4 items), breast satisfaction (2 items), and skin mucosis symptoms (6 items). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from Mixed Model Repeated Measures (MMRM) model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain (endocrine therapy symptoms, endocrine sexual symptoms, breast satisfaction and skin mucosis symptoms) was reported.
measure: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score
time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
description: EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for VAS was reported in this outcome measure.
measure: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value Score
time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
description: EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) & VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, & extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state & lower score indicate worse health state. LS mean and SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for health utility index value score was reported in this outcome measure.
measure: Time to First Chemotherapy
time frame: From randomization to the start date of the first chemotherapy (maximum exposure duration: 81 weeks)
description: Time to chemotherapy was defined as the time interval (in months) from the date of randomization to the start date of the first chemotherapy after disease progression.
measure: Number of Participants With Hematological Abnormalities During the Treatment Period
time frame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum exposure: 81 weeks)
description: Hematological parameters assessed were anemia, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, platelet count decreased. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 5.0 (NCI-CTCAE v 5.0), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment.
measure: Number of Participants With Liver Function Abnormalities of Grade 3 and 4 During the Treatment Period
time frame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum exposure: 81 weeks)
description: Liver Function parameters assessed were aspartate aminotransferase increased, alanine aminotransferase increased, alkaline phosphatase increased, total bilirubin increased, gamma-glutamyl transferase increased. Parameters were assessed as per the NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment. Participants with Grade 3 and 4 liver function abnormalities were reported in this outcome measure.
arm group label: Amcenestrant with Letrozole-matching placebo Arm
arm group type: Experimental
description: Participants in Amcenestrant with Letrozole-matching placebo Arm will be administered: Amcenestrant dose, once daily, continuously. Letrozole-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle. Goserelin once every 4 weeks in pre/peri menopausal women and men
arm group label: Letrozole with Amcenestrant matching placebo Arm
arm group type: Active Comparator
description: Participants in Letrozole with Amcenestrant-matching placebo Arm will be administered: Letrozole dose, once daily, continuously. Amcenestrant-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle Goserelin once every 4 weeks in pre/peri menopausal women and men
intervention type: Drug
intervention name: Amcenestrant-matching placebo
description: Pharmaceutical form: Tablets Route of Administration: Oral
arm group label: Letrozole with Amcenestrant matching placebo Arm
intervention type: Drug
intervention name: SAR439859
description: Pharmaceutical form: Tablets Route of Administration: Oral
arm group label: Amcenestrant with Letrozole-matching placebo Arm
other name: Amcenestrant
intervention type: Drug
intervention name: Palbociclib
description: Pharmaceutical form: Capsules/Tablets Route of Administration: Oral
arm group label: Amcenestrant with Letrozole-matching placebo Arm
arm group label: Letrozole with Amcenestrant matching placebo Arm
other name: Ibrance
intervention type: Drug
intervention name: Letrozole
description: Pharmaceutical form: Capsules Route of Administration: Orally
arm group label: Letrozole with Amcenestrant matching placebo Arm
intervention type: Drug
intervention name: Goserelin
description: Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous
arm group label: Amcenestrant with Letrozole-matching placebo Arm
arm group label: Letrozole with Amcenestrant matching placebo Arm
intervention type: Drug
intervention name: Letrozole-matching placebo
description: Pharmaceutical form: Capsules Route of Administration: Orally
arm group label: Amcenestrant with Letrozole-matching placebo Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
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country: Argentina
country: Australia
country: Austria
country: Belgium
country: Brazil
country: Bulgaria
country: Canada
country: Chile
country: China
country: Czechia
country: Finland
country: France
country: Georgia
country: Germany
country: Hungary
country: Italy
country: Japan
country: Korea, Republic of
country: Netherlands
country: Poland
country: Portugal
country: Russian Federation
country: Singapore
country: South Africa
country: Spain
country: Taiwan
country: Turkey
country: Ukraine
country: United Kingdom
country: United States
country: Estonia
country: Puerto Rico
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Letrozole
mesh term: Palbociclib
mesh term: Goserelin
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 terminated based on the review by an independent data monitoring committee of the prespecified interim analysis of the Phase 3 AMEERA-5 efficacy data.
point of contact: 