<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/NCT03776227</url>
  </required_header>
  <id_info>
    <org_study_id>BEQ14993</org_study_id>
    <secondary_id>U1111-1205-3319</secondary_id>
    <nct_id>NCT03776227</nct_id>
  </id_info>
  <brief_title>A Bioequivalence Study Testing Two Formulations of Sotagliflozin in Healthy Male and Female Subjects Under Fasted Conditions</brief_title>
  <official_title>A Bioequivalence Study Testing Two Formulations of Sotagliflozin in Healthy Male and Female Subjects Under Fasted Conditions</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>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 the bioequivalence of a single dose of one tablet of sotagliflozin (test)&#xD;
      compared to two tablets of sotagliflozin (reference) under fasting conditions in healthy male&#xD;
      and female subjects&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To evaluate the single-dose pharmacokinetics of sotagliflozin following administration&#xD;
           of one tablet sotagliflozin (test) compared to two tablets of sotagliflozin (reference)&#xD;
           in healthy male and female subjects under fasting conditions&#xD;
&#xD;
        -  To evaluate safety and tolerability of one tablet sotagliflozin (test) compared to two&#xD;
           tablets of sotagliflozin (reference) administered under fasted conditions in healthy&#xD;
           male and female subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study duration per participant is approximately 103 days including a screening period up to&#xD;
      21 days before first dose, 4 periods of dosing and pharmacokinetic (PK) sampling each lasting&#xD;
      7 days, a washout period of 8-21 days between dosing, and an end of study visit 10-15 days&#xD;
      after the last dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 25, 2019</start_date>
  <completion_date type="Actual">April 22, 2019</completion_date>
  <primary_completion_date type="Actual">April 22, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>Day 1 of each period</time_frame>
    <description>Maximum plasma concentration observed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC 0-72h (area under the curve)</measure>
    <time_frame>Day 1 to Day 3 of each period</time_frame>
    <description>Truncated AUC 0-72h</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to reach Cmax (tmax)</measure>
    <time_frame>Day 1 of each period</time_frame>
    <description>Time to reach Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2z)</measure>
    <time_frame>Day 1 to Day 7 of each period</time_frame>
    <description>Terminal half-life associated with the terminal slope (λz)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUClast)</measure>
    <time_frame>Day 1 to Day 7 of each period</time_frame>
    <description>Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Day 1 to Day 7 of each period</time_frame>
    <description>Number of participants with adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Electrocardiograms (ECGs)</measure>
    <time_frame>Day 1 to Day 7 of each period</time_frame>
    <description>Number of patients with clinically significant changes in electrocardiograms (ECGs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital signs</measure>
    <time_frame>Day 1 to Day 7 of each period</time_frame>
    <description>Number of patients with clinically significant changes in vital signs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical laboratory tests</measure>
    <time_frame>Day 1 to Day 7 of each period</time_frame>
    <description>Number of patients with clinically significant changes in clinical laboratory tests</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC)</measure>
    <time_frame>Day 1 to Day 7 of each period</time_frame>
    <description>Area under the plasma concentration versus time curve extrapolated to infinity</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Sotagliflozin Test</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One tablet of sotagliflozin administered orally under fasting conditions</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sotagliflozin Reference</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Two tablets of sotagliflozin administered orally under fasting conditions</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sotagliflozin (SAR439954)</intervention_name>
    <description>Pharmaceutical form: tablet&#xD;
Route of administration: oral</description>
    <arm_group_label>Sotagliflozin Reference</arm_group_label>
    <arm_group_label>Sotagliflozin Test</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Healthy male or female subjects, between 18 and 55 years of age, inclusive.&#xD;
&#xD;
          -  Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0&#xD;
             kg, inclusive, if female.&#xD;
&#xD;
          -  Body mass index between 18.0 and 30.0 kg/m2, inclusive.&#xD;
&#xD;
          -  Certified as healthy by a comprehensive clinical assessment (detailed medical history&#xD;
             and complete physical examination).&#xD;
&#xD;
          -  Normal vital signs after 10 minutes resting in supine position and after 3 minutes in&#xD;
             standing position:&#xD;
&#xD;
               -  95 mmHg &lt; systolic blood pressure (SBP) &lt;140 mmHg&#xD;
&#xD;
               -  45 mmHg &lt; diastolic blood pressure (DBP) &lt;90 mmHg&#xD;
&#xD;
               -  40 bpm &lt; heart rate (HR) &lt;100 bpm&#xD;
&#xD;
          -  Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine&#xD;
             position in the following ranges; 120 ms&lt;PR&lt;220 ms, QRS&lt;120 ms, QTc≤430 ms if male,&#xD;
             ≤450 ms if female and normal ECG tracing unless the Investigator considers an ECG&#xD;
             tracing abnormality to be not clinically relevant.&#xD;
&#xD;
          -  Laboratory parameters within the normal range, unless the Investigator considers an&#xD;
             abnormality to be clinically irrelevant for healthy subjects; however serum&#xD;
             creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine&#xD;
             aminotransferase), and total bilirubin (unless the subject has documented Gilbert&#xD;
             syndrome) should not exceed the upper laboratory norm.&#xD;
&#xD;
          -  Female subject must use a double contraception method including a highly effective&#xD;
             method of birth control, except if she has undergone sterilization at least 3 months&#xD;
             earlier or is postmenopausal. The accepted double contraception methods include the&#xD;
             use of 2 of the following 3 contraceptive options: (1) intrauterine device; (2)&#xD;
             hormonal contraception; (3) condom or diaphragm or cervical/vault cap, in addition to&#xD;
             spermicide. Menopause is defined as being amenorrheic for at least 2 years with plasma&#xD;
             follicule-stimulating hormone (FSH) level &gt;30 UI/L. Hormonal contraception is&#xD;
             acceptable in this study (contraceptive guidance will be described in the study&#xD;
             protocol).&#xD;
&#xD;
          -  Having given written informed consent prior to undertaking any study-related&#xD;
             procedure.&#xD;
&#xD;
          -  Not under any administrative or legal supervision.&#xD;
&#xD;
          -  Male subject, whose partners are of childbearing potential (including lactating&#xD;
             women), must accept to use, during sexual intercourse, a double contraception method&#xD;
             according to the following algorithm: (condom) plus (intra-uterine device or hormonal&#xD;
             contraceptive) from the inclusion up to 3 months after the last dosing. Male subject,&#xD;
             whose partners are pregnant, must use, during sexual intercourse, a condom from the&#xD;
             inclusion up to 3 months after the last dosing.&#xD;
&#xD;
          -  Male subject has agreed not to donate sperm from the inclusion up to 3 months after&#xD;
             the last dosing.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Any history or presence of clinically relevant cardiovascular, pulmonary,&#xD;
             gastrointestinal (especially pancreatitis), hepatic (especially biliary disease,&#xD;
             including cholecystectomy), renal, metabolic, hematological, neurological,&#xD;
             musculoskeletal, articular, psychiatric, systemic, ocular, gynecologic (if female), or&#xD;
             infectious disease, or signs of acute illness.&#xD;
&#xD;
          -  History of renal disease, or significantly abnormal kidney function test (glomerular&#xD;
             filtration rate (GFR) &lt;90 mL/min as calculated using the Cockcroft-Gault equation (7)&#xD;
             at screening.&#xD;
&#xD;
          -  Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice&#xD;
             a month).&#xD;
&#xD;
          -  Blood donation of a pint or more within 2 months before inclusion.&#xD;
&#xD;
          -  Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or&#xD;
             asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥20&#xD;
             mmHg within 3 minutes when changing from supine to standing position.&#xD;
&#xD;
          -  Presence or history of drug hypersensitivity, or allergic disease diagnosed and&#xD;
             treated by a physician.&#xD;
&#xD;
          -  History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per&#xD;
             day on a regular basis).&#xD;
&#xD;
          -  Smoking more than 5 cigarettes or equivalent per day and/or unable to stop smoking&#xD;
             during the study.&#xD;
&#xD;
          -  Excessive consumption of beverages containing xanthine bases (more than 4 cups or&#xD;
             glasses per day).&#xD;
&#xD;
          -  If female, pregnancy (defined as positive human chorionic gonadotropin (β-HCG blood&#xD;
             test), breast-feeding.&#xD;
&#xD;
          -  Any medication (over-the counter or prescription medications, including St John's&#xD;
             Wort), or any herbal supplements or supra-therapeutic vitamins within 14 days before&#xD;
             inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of&#xD;
             the substance; any vaccination within the last 28 days, and any biologics (antibody or&#xD;
             its derivatives) given within 4 months before inclusion.&#xD;
&#xD;
          -  Any subject who, in the judgment of the Investigator, is likely to be noncompliant&#xD;
             during the study, or unable to cooperate because of a language problem or poor mental&#xD;
             development.&#xD;
&#xD;
          -  Any subject in the exclusion period of a previous study according to applicable&#xD;
             regulations.&#xD;
&#xD;
          -  Any subject who cannot be contacted in case of emergency.&#xD;
&#xD;
          -  Any subject who is the Investigator or any sub-investigator, research assistant,&#xD;
             pharmacist, study coordinator, or other staff thereof, directly involved in conducting&#xD;
             the study.&#xD;
&#xD;
          -  Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen,&#xD;
             anti hepatitis C virus antibodies, anti-human immunodeficiency virus 1 and 2&#xD;
             antibodies (anti HIV1 and anti HIV2 Ab).&#xD;
&#xD;
          -  Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates,&#xD;
             benzodiazepines, cannabinoids, cocaine, opiates).&#xD;
&#xD;
          -  Positive alcohol test.&#xD;
&#xD;
          -  Any consumption of citrus (grapefruit, orange, etc) or their juices within 5 days&#xD;
             before inclusion.&#xD;
&#xD;
          -  Any history or presence of deep leg vein thrombosis or pulmonary embolism or a&#xD;
             recurrent or frequent history of deep vein thrombosis in first degree relatives&#xD;
             (parents, siblings or children).&#xD;
&#xD;
          -  Any presence or history of urinary tract infection or genital mycotic infection in the&#xD;
             last 4 weeks before screening.&#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>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</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 8400001</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>April 21, 2022</last_update_submitted>
  <last_update_submitted_qc>April 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 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, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol</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/NCT03776227
org study id: BEQ14993
secondary id: U1111-1205-3319
nct id: NCT03776227
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Primary Objective:

      To determine the bioequivalence of a single dose of one tablet of sotagliflozin (test)
      compared to two tablets of sotagliflozin (reference) under fasting conditions in healthy male
      and female subjects

      Secondary Objectives:

        -  To evaluate the single-dose pharmacokinetics of sotagliflozin following administration
           of one tablet sotagliflozin (test) compared to two tablets of sotagliflozin (reference)
           in healthy male and female subjects under fasting conditions

        -  To evaluate safety and tolerability of one tablet sotagliflozin (test) compared to two
           tablets of sotagliflozin (reference) administered under fasted conditions in healthy
           male and female subjects
Study duration per participant is approximately 103 days including a screening period up to
      21 days before first dose, 4 periods of dosing and pharmacokinetic (PK) sampling each lasting
      7 days, a washout period of 8-21 days between dosing, and an end of study visit 10-15 days
      after the last dose.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cmax
time frame: Day 1 of each period
description: Maximum plasma concentration observed
measure: AUC 0-72h (area under the curve)
time frame: Day 1 to Day 3 of each period
description: Truncated AUC 0-72h
measure: Time to reach Cmax (tmax)
time frame: Day 1 of each period
description: Time to reach Cmax
measure: Terminal half-life (t1/2z)
time frame: Day 1 to Day 7 of each period
description: Terminal half-life associated with the terminal slope (λz)
measure: Area under the plasma concentration versus time curve (AUClast)
time frame: Day 1 to Day 7 of each period
description: Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast
measure: Adverse events
time frame: Day 1 to Day 7 of each period
description: Number of participants with adverse events
measure: Electrocardiograms (ECGs)
time frame: Day 1 to Day 7 of each period
description: Number of patients with clinically significant changes in electrocardiograms (ECGs)
measure: Vital signs
time frame: Day 1 to Day 7 of each period
description: Number of patients with clinically significant changes in vital signs
measure: Clinical laboratory tests
time frame: Day 1 to Day 7 of each period
description: Number of patients with clinically significant changes in clinical laboratory tests
measure: Area under the curve (AUC)
time frame: Day 1 to Day 7 of each period
description: Area under the plasma concentration versus time curve extrapolated to infinity
arm group label: Sotagliflozin Test
arm group type: Experimental
description: One tablet of sotagliflozin administered orally under fasting conditions
arm group label: Sotagliflozin Reference
arm group type: Active Comparator
description: Two tablets of sotagliflozin administered orally under fasting conditions
intervention type: Drug
intervention name: sotagliflozin (SAR439954)
description: Pharmaceutical form: tablet
Route of administration: oral
arm group label: Sotagliflozin Reference
arm group label: Sotagliflozin Test
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
mesh term: (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
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