<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/NCT03798054</url>
  </required_header>
  <id_info>
    <org_study_id>EFC14943</org_study_id>
    <secondary_id>U1111-1190-7669</secondary_id>
    <nct_id>NCT03798054</nct_id>
  </id_info>
  <brief_title>Evaluation of Insulin Glargine/Lixisenatide Fixed Ratio Combination in Patients With Type 2 Diabetes Insufficiently Controlled With Oral Antidiabetic Drug(s)</brief_title>
  <acronym>Lixilan-O-AP</acronym>
  <official_title>A Randomized, 24 Week, Active-controlled, Open-label, 3-arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of iGlarLixi to Insulin Glargine and Lixisenatide in Type 2 Diabetes Mellitus Patients Insufficiently Controlled With Oral Antidiabetic Drug(s)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      The co-primary objective of this study is:&#xD;
&#xD;
        -  To demonstrate the superiority of iGlarLixi (fixed ratio combination of insulin glargine&#xD;
           and lixisenatide) versus lixisenatide on glycemic control as assessed by glycated&#xD;
           hemoglobin A1c (HbA1c) change.&#xD;
&#xD;
        -  To demonstrate the non-inferiority of iGlarLixi versus insulin glargine on glycemic&#xD;
           control as assessed by HbA1c change.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To assess the effects of iGlarLixi in comparison with insulin glargine alone and&#xD;
           lixisenatide alone.&#xD;
&#xD;
        -  To assess the safety in each treatment group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The maximum study duration per patient will be approximately 31 weeks: an up-to 6-week&#xD;
      screening and run-in period (with an up-to 2-week screening phase and a 4-week run-in phase),&#xD;
      followed by a 24-week randomized treatment period and a 3-day post-treatment safety follow up&#xD;
      period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2019</start_date>
  <completion_date type="Actual">March 1, 2021</completion_date>
  <primary_completion_date type="Actual">March 1, 2021</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Change in glycated hemoglobin (HbA1c) from baseline to Week 24</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in postprandial plasma glucose (PPG)</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Absolute change in 2-hour blood glucose excursion and PPG during meal test from baseline to Week 24 (for all patients in iGlarLixi or insulin glargine group and patients who receive morning injection in the lixisenatide group)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting plasma glucose (FPG)</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Absolute change in FPG from baseline to Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in self-monitored plasma glucose (SMPG) profile</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Absolute change in 7-point SMPG profiles from baseline to Week 24 (each time point and average daily value)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients with HbA1c &lt;7.0%</measure>
    <time_frame>At Week 24</time_frame>
    <description>Percentage of patients reaching HbA1c &lt;7% at Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients with HbA1c ≤ 6.5%</measure>
    <time_frame>At Week 24</time_frame>
    <description>Percentage of patients reaching HbA1c ≤ 6.5% at Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body weight</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Absolute change in body weight from baseline to Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients with HbA1c &lt;7.0% with no body weight gain</measure>
    <time_frame>At Week 24</time_frame>
    <description>Percentage of patients reaching HbA1c &lt;7% with no body weight gain at Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients with HbA1c &lt;7.0% with no body weight gain and no documented symptomatic hypoglycemia</measure>
    <time_frame>At Week 24</time_frame>
    <description>Percentage of patients reaching HbA1c &lt;7% with no body weight gain at Week 24 and no documented (plasma glucose [PG] ≤70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia during the 24 week treatment period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Confirmed hypoglycemia</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Including severe hypoglycemia and episodes of hypoglycemia documented with PG ≤70 mg/dL (3.9 mmol/L) regardless of symptoms from baseline to Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AEs)</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Number of AEs, serious AEs, AEs of Special Interest, and AEs requiring specific monitoring from baseline to Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity (antibody variables)</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Anti-lixisenatide antibodies and anti-insulin antibodies (depending on the treatment group) from baseline to Week 24</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">878</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Soliqua (insulin glargine/lixisenatide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>iGlarLixi (insulin glargine/lixisenatide) will be self-administered subcutaneously once daily in the morning on top of metformin for 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lantus (insulin glargine)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Insulin glargine will be self-administered subcutaneously once daily at any time of the day on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lyxumia (lixisenatide)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lixisenatide will be self-administered subcutaneously once daily according to the locally approved label on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin glargine/Lixisenatide (HOE901/AVE0010)</intervention_name>
    <description>Pharmaceutical form: solution&#xD;
Route of administration: subcutaneous</description>
    <arm_group_label>Soliqua (insulin glargine/lixisenatide)</arm_group_label>
    <other_name>Soliqua</other_name>
    <other_name>iGlarLixi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin glargine (HOE901)</intervention_name>
    <description>Pharmaceutical form: solution&#xD;
Route of administration: subcutaneous</description>
    <arm_group_label>Lantus (insulin glargine)</arm_group_label>
    <other_name>Lantus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lixisenatide (AVE0010)</intervention_name>
    <description>Pharmaceutical form: solution&#xD;
Route of administration: subcutaneous</description>
    <arm_group_label>Lyxumia (lixisenatide)</arm_group_label>
    <other_name>Lyxumia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Pharmaceutical form: tablet&#xD;
Route of administration: oral</description>
    <arm_group_label>Lantus (insulin glargine)</arm_group_label>
    <arm_group_label>Lyxumia (lixisenatide)</arm_group_label>
    <arm_group_label>Soliqua (insulin glargine/lixisenatide)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SGLT2 inhibitor</intervention_name>
    <description>Pharmaceutical form:tablet&#xD;
Route of administration: oral</description>
    <arm_group_label>Lantus (insulin glargine)</arm_group_label>
    <arm_group_label>Lyxumia (lixisenatide)</arm_group_label>
    <arm_group_label>Soliqua (insulin glargine/lixisenatide)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the&#xD;
             screening visit (V1), treated for at least 3 months prior to the screening visit (V1)&#xD;
             with metformin alone or metformin and a second oral antidiabetic treatment that can be&#xD;
             a sulfonylurea (SU), a glinide, an alpha-glucosidase inhibitor (alpha-GI), a&#xD;
             dipeptidyl peptidase-4 (DPP-4) inhibitor or a sodium-glucose co transporter 2 (SGLT-2)&#xD;
             inhibitor and who are not adequately controlled with this treatment.&#xD;
&#xD;
          -  Signed written informed consent.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Age &lt; legal age of majority at the screening visit (V1).&#xD;
&#xD;
          -  Body mass index (BMI) &gt;40 kg/m² at screening.&#xD;
&#xD;
          -  Glycated hemoglobin A1c (HbA1c) at screening visit:&#xD;
&#xD;
          -  &lt;7.5% or &gt;11% for patients previously treated with metformin alone;&#xD;
&#xD;
          -  &lt;7.0% or &gt;10% for patients previously treated with metformin and a second oral&#xD;
             antidiabetic treatment.&#xD;
&#xD;
          -  History of hypoglycemia unawareness.&#xD;
&#xD;
          -  History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to&#xD;
             screening.&#xD;
&#xD;
          -  Use of oral or injectable glucose-lowering agents other than those stated in the&#xD;
             inclusion criteria within 3 months prior to screening.&#xD;
&#xD;
          -  Previous treatment with insulin (except for short-term treatment due to intercurrent&#xD;
             illness at the discretion of the Investigator) within 1 year prior to screening.&#xD;
&#xD;
          -  History of discontinuation of a previous treatment with glucagon-like-peptide-1&#xD;
             receptor agonists (GLP-1 RAs) due to safety/tolerability reasons or lack of efficacy.&#xD;
&#xD;
          -  Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1&#xD;
             week or more within 3 months prior to screening.&#xD;
&#xD;
          -  Use of weight loss drugs within 3 months prior to screening.&#xD;
&#xD;
          -  Use of any investigational drug other than specified in this protocol within 1 month&#xD;
             or 5 half-lives, whichever is longer, prior to screening.&#xD;
&#xD;
          -  Within 6 months prior to screening: history of myocardial infarction, stroke, or heart&#xD;
             failure requiring hospitalization.&#xD;
&#xD;
          -  Planned coronary, carotid, or peripheral artery revascularization procedures to be&#xD;
             performed during the study period.&#xD;
&#xD;
          -  Known history of drug or alcohol abuse within 6 months prior to screening.&#xD;
&#xD;
          -  Uncontrolled or inadequately controlled hypertension at the time of screening with a&#xD;
             resting systolic blood pressure &gt;180 mmHg or diastolic blood pressure &gt;95 mmHg.&#xD;
&#xD;
          -  Laboratory findings at screening visit (V1):&#xD;
&#xD;
          -  Amylase and/or lipase &gt;3 times the upper limit of normal (ULN) laboratory range.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &gt;3 ULN.&#xD;
&#xD;
          -  Total bilirubin &gt;1.5 ULN (except in case of Gilbert's syndrome).&#xD;
&#xD;
          -  Calcitonin ≥20 pg/mL (5.9 pmol/L).&#xD;
&#xD;
          -  Hemoglobin &lt;10.5 g/dL and/or neutrophils &lt;1500/mm3 and/or platelets &lt;100 000/mm3.&#xD;
&#xD;
          -  Positive urine pregnancy test in female of childbearing potential.&#xD;
&#xD;
          -  Patient who has a severe renal function impairment with an estimated glomerular&#xD;
             filtration rate (eGFR) &lt;30 mL/min/1.73m2 or end-stage renal disease.&#xD;
&#xD;
          -  History of pancreatitis (unless pancreatitis was related to gallstones and&#xD;
             cholecystectomy has been performed), pancreatitis during previous treatment with&#xD;
             incretin therapies, chronic pancreatitis, pancreatectomy.&#xD;
&#xD;
          -  Personal or immediate family history of medullary thyroid cancer (MTC) or genetic&#xD;
             conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).&#xD;
&#xD;
          -  Use of SU, glinide, alpha-GI, DPP-4 inhibitor, and SGLT-2 inhibitor after start of&#xD;
             run-in (from V2 [Week -4]).&#xD;
&#xD;
          -  HbA1c at V4 (Week -1) : &lt;7.0% or &gt;10%.&#xD;
&#xD;
          -  Fasting plasma glucose &gt;250 mg/dL (13.9 mmol/L) at V4 (Week-1) (can be repeated once&#xD;
             to confirm).&#xD;
&#xD;
          -  Metformin maximal tolerated dose &lt;1500 mg/day.&#xD;
&#xD;
          -  Amylase and/or lipase &gt;3 ULN at V4 (Week-1).&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a patient's&#xD;
        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 1560001</name>
      <address>
        <city>Beijing</city>
        <zip>1000029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560006</name>
      <address>
        <city>Beijing</city>
        <zip>101200</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560049</name>
      <address>
        <city>Beijing</city>
        <zip>102218</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560039</name>
      <address>
        <city>Cangzhou</city>
        <zip>061000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560009</name>
      <address>
        <city>Changchun</city>
        <zip>130033</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560027</name>
      <address>
        <city>Changchun</city>
        <zip>130041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560016</name>
      <address>
        <city>Changsha</city>
        <zip>410013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560053</name>
      <address>
        <city>Chengdu</city>
        <zip>610081</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560056</name>
      <address>
        <city>Chengdu</city>
        <zip>611130</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560010</name>
      <address>
        <city>Chenzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560037</name>
      <address>
        <city>Chongqing</city>
        <zip>400010</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560050</name>
      <address>
        <city>Chongqing</city>
        <zip>400013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560044</name>
      <address>
        <city>Dongguan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560033</name>
      <address>
        <city>Guangzhou</city>
        <zip>510120</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560028</name>
      <address>
        <city>Guangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560012</name>
      <address>
        <city>Handan</city>
        <zip>056002</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560023</name>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560035</name>
      <address>
        <city>Harbin</city>
        <zip>150001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560036</name>
      <address>
        <city>Harbin</city>
        <zip>150001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560011</name>
      <address>
        <city>Hengshui</city>
        <zip>053000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560024</name>
      <address>
        <city>Hohhot</city>
        <zip>010017</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560047</name>
      <address>
        <city>Hohhot</city>
        <zip>010050</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 3440001</name>
      <address>
        <city>Hong Kong</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560025</name>
      <address>
        <city>Huang Shi</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560026</name>
      <address>
        <city>Huanggang</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560048</name>
      <address>
        <city>Huizhou</city>
        <zip>516001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560034</name>
      <address>
        <city>Huzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560005</name>
      <address>
        <city>Jinan</city>
        <zip>250013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560052</name>
      <address>
        <city>Jinhua</city>
        <zip>321000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560031</name>
      <address>
        <city>Jinzhou</city>
        <zip>121000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560022</name>
      <address>
        <city>Nanjing</city>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560014</name>
      <address>
        <city>Nanjing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560043</name>
      <address>
        <city>Nanjing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560041</name>
      <address>
        <city>Nanning</city>
        <zip>530021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560032</name>
      <address>
        <city>Qingdao</city>
        <zip>266042</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560038</name>
      <address>
        <city>Qinhuangdao</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560013</name>
      <address>
        <city>Shanghai</city>
        <zip>200072</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560007</name>
      <address>
        <city>Shanghai</city>
        <zip>200240</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560004</name>
      <address>
        <city>Shanghai</city>
        <zip>201700</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560029</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560003</name>
      <address>
        <city>Shenyang</city>
        <zip>110022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560054</name>
      <address>
        <city>Shenzhen</city>
        <zip>518000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560019</name>
      <address>
        <city>Suzhou</city>
        <zip>215006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560059</name>
      <address>
        <city>Suzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560021</name>
      <address>
        <city>Tianjin</city>
        <zip>300052</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560017</name>
      <address>
        <city>Tianjin</city>
        <zip>300121</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560058</name>
      <address>
        <city>Urumqi</city>
        <zip>830000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560018</name>
      <address>
        <city>Wuhan</city>
        <zip>430014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560008</name>
      <address>
        <city>Xi'An</city>
        <zip>710061</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560055</name>
      <address>
        <city>Xi'An</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560051</name>
      <address>
        <city>Xingtai</city>
        <zip>054031</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560030</name>
      <address>
        <city>Xining</city>
        <zip>810007</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560040</name>
      <address>
        <city>Yanji</city>
        <zip>133000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560060</name>
      <address>
        <city>Yueyang</city>
        <zip>414000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560046</name>
      <address>
        <city>Yueyang</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560045</name>
      <address>
        <city>Zhengzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560002</name>
      <address>
        <city>Zhenjiang</city>
        <zip>212001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560015</name>
      <address>
        <city>Zhuzhou</city>
        <zip>412007</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1560057</name>
      <address>
        <city>Zigong</city>
        <zip>643002</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100009</name>
      <address>
        <city>Ansan-Si</city>
        <zip>15355</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100012</name>
      <address>
        <city>Busan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100010</name>
      <address>
        <city>Guri-Si, Gyeonggi-Do</city>
        <zip>11923</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100004</name>
      <address>
        <city>Gwangju</city>
        <zip>61469</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100003</name>
      <address>
        <city>Seongnam-Si</city>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100016</name>
      <address>
        <city>Seoul</city>
        <zip>01832</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100011</name>
      <address>
        <city>Seoul</city>
        <zip>03181</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100013</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100001</name>
      <address>
        <city>Seoul</city>
        <zip>05278</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100002</name>
      <address>
        <city>Seoul</city>
        <zip>08308</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4100005</name>
      <address>
        <city>Wonju</city>
        <zip>26426</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4580001</name>
      <address>
        <city>Kelantan</city>
        <zip>16150</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4580005</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>56000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4580003</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>59100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4580006</name>
      <address>
        <city>Kuching</city>
        <zip>93586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4580002</name>
      <address>
        <city>Putrajaya</city>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 4580004</name>
      <address>
        <city>Seremban</city>
        <zip>70300</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1580003</name>
      <address>
        <city>Taichung</city>
        <zip>407</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1580005</name>
      <address>
        <city>Tainan Hsien</city>
        <zip>710</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 1580004</name>
      <address>
        <city>Taipei</city>
        <zip>11031</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
    <country>Korea, Republic of</country>
    <country>Malaysia</country>
    <country>Taiwan</country>
  </location_countries>
  <removed_countries>
    <country>Hong Kong</country>
  </removed_countries>
  <reference>
    <citation>Yang W, Dong X, Li Q, Cheng Z, Yuan G, Liu M, Xiao J, Gu S, Niemoeller E, Chen L, Ping L, Souhami E; LixiLan-O-AP trial investigators. Efficacy and safety benefits of iGlarLixi versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with suboptimally controlled type 2 diabetes on oral agents: The LixiLan-O-AP randomized controlled trial. Diabetes Obes Metab. 2022 Aug;24(8):1522-1533. doi: 10.1111/dom.14722. Epub 2022 May 12.</citation>
    <PMID>35441412</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>July 14, 2022</last_update_submitted>
  <last_update_submitted_qc>July 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Insulin Glargine</mesh_term>
    <mesh_term>Lixisenatide</mesh_term>
    <mesh_term>Sodium-Glucose Transporter 2 Inhibitors</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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03798054
org study id: EFC14943
secondary id: U1111-1190-7669
nct id: NCT03798054
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Primary Objectives:

      The co-primary objective of this study is:

        -  To demonstrate the superiority of iGlarLixi (fixed ratio combination of insulin glargine
           and lixisenatide) versus lixisenatide on glycemic control as assessed by glycated
           hemoglobin A1c (HbA1c) change.

        -  To demonstrate the non-inferiority of iGlarLixi versus insulin glargine on glycemic
           control as assessed by HbA1c change.

      Secondary Objectives:

        -  To assess the effects of iGlarLixi in comparison with insulin glargine alone and
           lixisenatide alone.

        -  To assess the safety in each treatment group.
The maximum study duration per patient will be approximately 31 weeks: an up-to 6-week
      screening and run-in period (with an up-to 2-week screening phase and a 4-week run-in phase),
      followed by a 24-week randomized treatment period and a 3-day post-treatment safety follow up
      period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in HbA1c
time frame: From Baseline to Week 24
description: Change in glycated hemoglobin (HbA1c) from baseline to Week 24
measure: Change in postprandial plasma glucose (PPG)
time frame: From Baseline to Week 24
description: Absolute change in 2-hour blood glucose excursion and PPG during meal test from baseline to Week 24 (for all patients in iGlarLixi or insulin glargine group and patients who receive morning injection in the lixisenatide group)
measure: Change in fasting plasma glucose (FPG)
time frame: From Baseline to Week 24
description: Absolute change in FPG from baseline to Week 24
measure: Change in self-monitored plasma glucose (SMPG) profile
time frame: From Baseline to Week 24
description: Absolute change in 7-point SMPG profiles from baseline to Week 24 (each time point and average daily value)
measure: Patients with HbA1c <7.0%
time frame: At Week 24
description: Percentage of patients reaching HbA1c <7% at Week 24
measure: Patients with HbA1c ≤ 6.5%
time frame: At Week 24
description: Percentage of patients reaching HbA1c ≤ 6.5% at Week 24
measure: Change in body weight
time frame: From Baseline to Week 24
description: Absolute change in body weight from baseline to Week 24
measure: Patients with HbA1c <7.0% with no body weight gain
time frame: At Week 24
description: Percentage of patients reaching HbA1c <7% with no body weight gain at Week 24
measure: Patients with HbA1c <7.0% with no body weight gain and no documented symptomatic hypoglycemia
time frame: At Week 24
description: Percentage of patients reaching HbA1c <7% with no body weight gain at Week 24 and no documented (plasma glucose [PG] ≤70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia during the 24 week treatment period
measure: Confirmed hypoglycemia
time frame: From Baseline to Week 24
description: Including severe hypoglycemia and episodes of hypoglycemia documented with PG ≤70 mg/dL (3.9 mmol/L) regardless of symptoms from baseline to Week 24
measure: Adverse events (AEs)
time frame: From Baseline to Week 24
description: Number of AEs, serious AEs, AEs of Special Interest, and AEs requiring specific monitoring from baseline to Week 24
measure: Immunogenicity (antibody variables)
time frame: From Baseline to Week 24
description: Anti-lixisenatide antibodies and anti-insulin antibodies (depending on the treatment group) from baseline to Week 24
arm group label: Soliqua (insulin glargine/lixisenatide)
arm group type: Experimental
description: iGlarLixi (insulin glargine/lixisenatide) will be self-administered subcutaneously once daily in the morning on top of metformin for 24 weeks.
arm group label: Lantus (insulin glargine)
arm group type: Active Comparator
description: Insulin glargine will be self-administered subcutaneously once daily at any time of the day on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period.
arm group label: Lyxumia (lixisenatide)
arm group type: Active Comparator
description: Lixisenatide will be self-administered subcutaneously once daily according to the locally approved label on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period.
intervention type: Drug
intervention name: Insulin glargine/Lixisenatide (HOE901/AVE0010)
description: Pharmaceutical form: solution
Route of administration: subcutaneous
arm group label: Soliqua (insulin glargine/lixisenatide)
other name: Soliqua
other name: iGlarLixi
intervention type: Drug
intervention name: Insulin glargine (HOE901)
description: Pharmaceutical form: solution
Route of administration: subcutaneous
arm group label: Lantus (insulin glargine)
other name: Lantus
intervention type: Drug
intervention name: Lixisenatide (AVE0010)
description: Pharmaceutical form: solution
Route of administration: subcutaneous
arm group label: Lyxumia (lixisenatide)
other name: Lyxumia
intervention type: Drug
intervention name: Metformin
description: Pharmaceutical form: tablet
Route of administration: oral
arm group label: Lantus (insulin glargine)
arm group label: Lyxumia (lixisenatide)
arm group label: Soliqua (insulin glargine/lixisenatide)
intervention type: Drug
intervention name: SGLT2 inhibitor
description: Pharmaceutical form:tablet
Route of administration: oral
arm group label: Lantus (insulin glargine)
arm group label: Lyxumia (lixisenatide)
arm group label: Soliqua (insulin glargine/lixisenatide)
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: China
country: Korea, Republic of
country: Malaysia
country: Taiwan
country: Hong Kong
citation: Yang W, Dong X, Li Q, Cheng Z, Yuan G, Liu M, Xiao J, Gu S, Niemoeller E, Chen L, Ping L, Souhami E; LixiLan-O-AP trial investigators. Efficacy and safety benefits of iGlarLixi versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with suboptimally controlled type 2 diabetes on oral agents: The LixiLan-O-AP randomized controlled trial. Diabetes Obes Metab. 2022 Aug;24(8):1522-1533. doi: 10.1111/dom.14722. Epub 2022 May 12.
PMID: 35441412
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Metformin
mesh term: Insulin Glargine
mesh term: Lixisenatide
mesh term: Sodium-Glucose Transporter 2 Inhibitors
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