<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/NCT02201004</url>
  </required_header>
  <id_info>
    <org_study_id>TOFOGL07061</org_study_id>
    <secondary_id>U1111-1159-5316</secondary_id>
    <nct_id>NCT02201004</nct_id>
  </id_info>
  <brief_title>TOFO Insulin Combination Trial</brief_title>
  <official_title>A Randomized, Double Blind Placebo Controlled 2-Arm Parallel Group, Multicenter Study With A 16-Week Treatment Assessing The Efficacy And Safety, And 52-Week Long Term Safety Including 36-Week Open Label Extension Of Tofogliflozin With Insulin Treatment In Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kowa Company, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      To assess the effects of tofogliflozin on glycemic control in comparison to placebo as an&#xD;
      add-on treatment to insulin treatment in terms of glycated hemoglobin (HbA1c) reduction over&#xD;
      a period of 16 weeks in patients with type 2 diabetes mellitus.&#xD;
&#xD;
      To assess the safety of tofogliflozin in combination with insulin treatment throughout 52&#xD;
      weeks.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
      To assess the effects of tofogliflozin in comparison to placebo on:&#xD;
&#xD;
        -  Body weight&#xD;
&#xD;
        -  Fasting plasma glucose (FPG)&#xD;
&#xD;
        -  Postprandial plasma glucose (PPG) To assess the long term safety and tolerability of&#xD;
           tofogliflozin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The total study duration from screening for a patient can be approximately up to 1 year,&#xD;
      including a screening period of 2 weeks, double-blinded placebo controlled treatment period&#xD;
      of 16 weeks, an open-labeled extension period of 36 weeks, and a follow-up period of 3 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>Phase 4</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c from baseline</measure>
    <time_frame>16 weeks after first intake of investigational product</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of Body Weight (BW) from baseline</measure>
    <time_frame>16 weeks after first intake of investigational product</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of FPG from baseline</measure>
    <time_frame>16 weeks after first intake of investigational product</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of PPG from baseline</measure>
    <time_frame>16 weeks after first intake of investigational product</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>Up to 52 weeks from the first intake of investigational medicinal product</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">211</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>tofogliflozin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tofogliflozin administered once daily for 52 weeks. Insulin administered as base treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered once daily for 16 weeks. After 16-weeks, Tofogliflozin administered once daily for 36 weeks. Insulin administered as base treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TOFOGLIFLOZIN CSG452</intervention_name>
    <description>Pharmaceutical form:tablet Route of administration: oral</description>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_label>tofogliflozin</arm_group_label>
    <other_name>Apleway</other_name>
    <other_name>Deberza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin</intervention_name>
    <description>Pharmaceutical form:solution Route of administration: subcutaneous</description>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_label>tofogliflozin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Pharmaceutical form:tablet Route of administration: oral</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patients aged 20-75 years old with type 2 diabetes mellitus (T2DM).&#xD;
&#xD;
          -  Hemoglobin A1c ≥7.5% - ≤10.5% and FPG ≤220 mg/dL.&#xD;
&#xD;
          -  Basal bolus (BB), Bolus, Premix, Basal supported oral therapy (BOT) regimens used for&#xD;
             more than 12 weeks before screening.&#xD;
&#xD;
          -  Stable dose (-/+20%) of insulin and no change in the dose of oral hypoglycemic agents&#xD;
             for more than 12 weeks before screening.&#xD;
&#xD;
          -  Only Dipeptidyl peptidase-4 inhibitor is allowed for basal supported oral therapy&#xD;
             (BOT) regimen.&#xD;
&#xD;
          -  Body mass index (BMI) ≥18.5 kg/m^2 and &lt;35.0 kg/m^2.&#xD;
&#xD;
          -  No change of antihypertensive, anti-hypercholesterolemia and uric acid lowering drug 4&#xD;
             weeks before screening.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Type 1 diabetes mellitus.&#xD;
&#xD;
          -  Pregnancy or lactation.&#xD;
&#xD;
          -  Severely uncontrolled glycemic situation.&#xD;
&#xD;
          -  History of metabolic acidosis, including diabetic ketoacidosis, within 1 year prior to&#xD;
             screening.&#xD;
&#xD;
          -  History of myocardial infarction, stroke, or heart failure requiring hospitalization&#xD;
             or drug or alcohol abuse within the previous 6 months.&#xD;
&#xD;
          -  A measured serum creatinine level greater than 2.0 mg/dL for men and 1.5 mg/dL for&#xD;
             women.&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 times the&#xD;
             upper limit of the reference range at the central laboratory test facility.&#xD;
&#xD;
          -  Has previously received treatment with the investigational product.&#xD;
&#xD;
          -  Has received treatment with another investigational product or non-approved drug&#xD;
             within 3 months before tests for provisional enrolment.&#xD;
&#xD;
          -  Corticosteroid therapy for 14 or more days in total within 8 weeks before tests for&#xD;
             provisional enrolment (excluding those used for localized effects, such as drugs for&#xD;
             topical [skin] application, eye drops and sprays).&#xD;
&#xD;
          -  Patients who are frequently experiencing orthostatic hypotension.&#xD;
&#xD;
          -  Required a change in the dosing regimen for the following drugs within 4 weeks before&#xD;
             tests for provisional enrolment:&#xD;
&#xD;
          -  Lipid-lowering drug&#xD;
&#xD;
          -  Antihypertensive drug&#xD;
&#xD;
          -  Thyroid hormone preparation&#xD;
&#xD;
          -  Uric acid lowering drug&#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>20 Years</minimum_age>
    <maximum_age>75 Years</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 392-028</name>
      <address>
        <city>Adachi-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-007</name>
      <address>
        <city>Atsugi-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-026</name>
      <address>
        <city>Chuoh-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-021</name>
      <address>
        <city>Fukuoka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-002</name>
      <address>
        <city>Ichihara-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-012</name>
      <address>
        <city>Iruma-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-003</name>
      <address>
        <city>Kawaguchi-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-014</name>
      <address>
        <city>Kitakyusyu-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-027</name>
      <address>
        <city>Kobe-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-004</name>
      <address>
        <city>Koga-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-022</name>
      <address>
        <city>Kunitachi-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-019</name>
      <address>
        <city>Kurume-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-001</name>
      <address>
        <city>Kyoto-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-024</name>
      <address>
        <city>Kyoto-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-006</name>
      <address>
        <city>Matsudo-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-008</name>
      <address>
        <city>Mito-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-030</name>
      <address>
        <city>Musashino-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-029</name>
      <address>
        <city>Okayama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-017</name>
      <address>
        <city>Otsu-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-011</name>
      <address>
        <city>Sagamihara-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-020</name>
      <address>
        <city>Sakai-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-010</name>
      <address>
        <city>Sapporo-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-016</name>
      <address>
        <city>Sendai-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-018</name>
      <address>
        <city>Shinjuku-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-005</name>
      <address>
        <city>Shizuoka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-031</name>
      <address>
        <city>Suita-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-015</name>
      <address>
        <city>Sumida-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-023</name>
      <address>
        <city>Sunto-gun</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-013</name>
      <address>
        <city>Tokorozawa-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392-025</name>
      <address>
        <city>Yokohama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <results_reference>
    <citation>Terauchi Y, Tamura M, Senda M, Gunji R, Kaku K. Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial. Diabetes Obes Metab. 2017 Oct;19(10):1397-1407. doi: 10.1111/dom.12957. Epub 2017 Jul 13.</citation>
    <PMID>28371205</PMID>
  </results_reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>October 10, 2017</last_update_submitted>
  <last_update_submitted_qc>October 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2017</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>6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02201004
org study id: TOFOGL07061
secondary id: U1111-1159-5316
nct id: NCT02201004
lead sponsor: 
collaborator: 
has dmc: No
Primary Objectives:

      To assess the effects of tofogliflozin on glycemic control in comparison to placebo as an
      add-on treatment to insulin treatment in terms of glycated hemoglobin (HbA1c) reduction over
      a period of 16 weeks in patients with type 2 diabetes mellitus.

      To assess the safety of tofogliflozin in combination with insulin treatment throughout 52
      weeks.

      Secondary Objectives:

      To assess the effects of tofogliflozin in comparison to placebo on:

        -  Body weight

        -  Fasting plasma glucose (FPG)

        -  Postprandial plasma glucose (PPG) To assess the long term safety and tolerability of
           tofogliflozin.
The total study duration from screening for a patient can be approximately up to 1 year,
      including a screening period of 2 weeks, double-blinded placebo controlled treatment period
      of 16 weeks, an open-labeled extension period of 36 weeks, and a follow-up period of 3 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in HbA1c from baseline
time frame: 16 weeks after first intake of investigational product
measure: Change of Body Weight (BW) from baseline
time frame: 16 weeks after first intake of investigational product
measure: Change of FPG from baseline
time frame: 16 weeks after first intake of investigational product
measure: Change of PPG from baseline
time frame: 16 weeks after first intake of investigational product
measure: Number of subjects with adverse events
time frame: Up to 52 weeks from the first intake of investigational medicinal product
arm group label: tofogliflozin
arm group type: Experimental
description: Tofogliflozin administered once daily for 52 weeks. Insulin administered as base treatment.
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo administered once daily for 16 weeks. After 16-weeks, Tofogliflozin administered once daily for 36 weeks. Insulin administered as base treatment.
intervention type: Drug
intervention name: TOFOGLIFLOZIN CSG452
description: Pharmaceutical form:tablet Route of administration: oral
arm group label: placebo
arm group label: tofogliflozin
other name: Apleway
other name: Deberza
intervention type: Drug
intervention name: insulin
description: Pharmaceutical form:solution Route of administration: subcutaneous
arm group label: placebo
arm group label: tofogliflozin
intervention type: Drug
intervention name: placebo
description: Pharmaceutical form:tablet Route of administration: oral
arm group label: placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 75 Years
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
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country: Japan
citation: Terauchi Y, Tamura M, Senda M, Gunji R, Kaku K. Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial. Diabetes Obes Metab. 2017 Oct;19(10):1397-1407. doi: 10.1111/dom.12957. Epub 2017 Jul 13.
PMID: 28371205
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol