<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/NCT03811548</url>
  </required_header>
  <id_info>
    <org_study_id>5695-DIA-3001</org_study_id>
    <nct_id>NCT03811548</nct_id>
  </id_info>
  <brief_title>Janagliflozin Treat T2DM Monotherapy</brief_title>
  <official_title>A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled Study, to Evaluate the Efficacy and Safety of Janagliflozin (25 mg and 50 mg) as Monotherapy in Chinese Patients Diagnosed With T2DM</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sihuan Pharmaceutical Holdings Group Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sihuan Pharmaceutical Holdings Group Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to assess the effect of Janagliflozin relative to placebo on&#xD;
      glycated hemoglobin (HbA1c) after 24 weeks of treatment, and to assess the efficacy after 52&#xD;
      weeks of treatment, overall safety and Population pharmacokinetics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A multicentre, randomized, double-blind, parallel group, placebo-controlled study(24 weeks&#xD;
      core period followed by 28 Weeks Extension period), to evaluate the efficacy and safety of&#xD;
      Janagliflozin (25 mg and 50 mg) compared to placebo in patients diagnosed with T2DM who are&#xD;
      not achieving an adequate response from diet and exercise to control their diabetes.&#xD;
      Approximately 390 patients with inadequate glycemic control with diet and exercise will&#xD;
      receive once-daily double-blind treatment with Janagliflozin 25 mg or 50 mg once daily for 52&#xD;
      weeks, or 24 weeks of double-blind treatment with placebo followed by 28 weeks of&#xD;
      single-blind treatment with Janagliflozin 25 mg or 50 mg. During the treatment, if a&#xD;
      patient's glycemic level remains high despite treatment with study drug and reinforcement&#xD;
      with diet and exercise, the patient will receive treatment with metformin (rescue therapy)&#xD;
      consistent with local prescribing information. Study drug will be taken orally once daily.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 23, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">June 24, 2020</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>
    <masking_description>Double Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c From Baseline to Week 24</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>To examine whether the mean change in HbA1c from baseline to week 24 with Janagliflozin is superiority (superiority margin of 0.5%) to placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in HbA1c From Baseline to Week 52</measure>
    <time_frame>Baseline and Week 52</time_frame>
    <description>To compare the mean change in HbA1c from baseline to week 52 between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With HbA1c &lt;7% at Week 24 (Core period) and week 52</measure>
    <time_frame>Baseline, Week 24 and week 52</time_frame>
    <description>To compare the percentage of patients with HbA1c &lt;7% at week 24 (core period) and week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With HbA1c &lt;6.5% at Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the percentage of patients with HbA1c &lt;6.5% at week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in fasting plasma glucose (FPG) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 2-hour Post-prandial Glucose From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in 2-hour post-prandial glucose from Baseline to Week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Blood Lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in blood lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Blood Pressure (systolic blood pressure and diastolic blood pressure) From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in blood pressure (systolic blood pressure and diastolic blood pressure) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Weight From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in body weight from Baseline to Week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting C-peptide From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in fasting C-peptide from Baseline to Week 24 (core period) and Week 52 (extension period) between groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Insulin Sensitivity From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in insulin sensitivity from Baseline to Week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in β-cell Function From Baseline to Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Baseline, Week 24 and Week 52</time_frame>
    <description>To compare the mean change in β-cell function from Baseline to Week 24 (core period) and Week 52 (extension period) between groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Who Have Received Rescue Therapy at Week 24 (Core period) and Week 52 (Extension period)</measure>
    <time_frame>Week 24 and Week 52</time_frame>
    <description>To compare the percentage of patients who have received rescue therapy by Week 24 (core period) and Week 52 (extension period) between groups</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Urinary albumin/creatinine ratio (UACR)</measure>
    <time_frame>From Baseline to Week 52</time_frame>
    <description>To evaluate Urinary albumin/creatinine ratio in different group</description>
  </other_outcome>
  <other_outcome>
    <measure>Occurrence of adverse events</measure>
    <time_frame>From Baseline to Week 52</time_frame>
    <description>To evaluate adverse events in different group</description>
  </other_outcome>
  <other_outcome>
    <measure>Occurrence of hypoglycaemic episodes</measure>
    <time_frame>From Baseline to Week 52</time_frame>
    <description>To evaluate adverse events in different group</description>
  </other_outcome>
  <other_outcome>
    <measure>Population pharmacokinetics assessment</measure>
    <time_frame>Baseline, Week 2, Week4, Week8, Week24</time_frame>
    <description>By compare patients' Minimum Plasma Concentration (on week 2, 4, 8, 24)to eveluate Janagliflozin population pharmacokinetics characteristics</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">442</enrollment>
  <condition>Diabetes Type 2</condition>
  <arm_group>
    <arm_group_label>Janagliflozin 25mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will receive 25 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Janagliflozin 50mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will receive 50 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo/Janagliflozin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the core period, each patient will receive placebo once daily for 24 weeks and will then switch from placebo to 25 mg or 50 mg of Janagliflozin once daily until Week 52.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Janagliflozin 25mg</intervention_name>
    <description>Tablets, Oral, 25 mg, Tablets, Oral, 50 mg</description>
    <arm_group_label>Janagliflozin 25mg</arm_group_label>
    <other_name>Placebo 50mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Janagliflozin 50mg</intervention_name>
    <description>Tablets, Oral, 25 mg, Once daily, 52 weeks</description>
    <arm_group_label>Janagliflozin 50mg</arm_group_label>
    <other_name>Placebo 25mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo/Janagliflozin</intervention_name>
    <description>Tablets, Oral, 25 mg, Once daily, 52 weeks</description>
    <arm_group_label>Placebo/Janagliflozin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients must have a diagnosis of T2DM (meet the diagnostic criteria for diabetes&#xD;
             issued by the World Health Organization in 1999)&#xD;
&#xD;
          -  Patients must have a hemoglobin A1c (HbA1c) level ≥7.5% and ≤11% at screening, and&#xD;
             ≥7.0% and ≤10.5% at baseline.&#xD;
&#xD;
          -  Drug -naïve (never received anti-diabetic medication or did not receive anti-diabetic&#xD;
             medication within 8 weeks before screening).&#xD;
&#xD;
          -  Body Mass Index: 18.0~35.0 kg/m2 (both inclusive)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of type 1 diabetes mellitus (T1DM), diabetes caused by pancreatic injury, or&#xD;
             secondary diabetes (e.g., diabetes caused by Cushing's syndrome or acromegaly)&#xD;
&#xD;
          -  More than 10% change in body weight within the 3 months before screening&#xD;
&#xD;
          -  Any laboratory test indicators meet the following standards:&#xD;
&#xD;
               -  fasting plasma glucose ≥ 15 mmol/L&#xD;
&#xD;
               -  aspartate aminotransferase, alanine aminotransferase levels &gt; 3 times the upper&#xD;
                  limit of normal (ULN); total bilirubin &gt; 1.5 times ULN&#xD;
&#xD;
               -  hemoglobin &lt; 100 g/L&#xD;
&#xD;
               -  eGFR &lt; 60 mL/min/1.73m2&#xD;
&#xD;
               -  fasting triglycerides &gt; 5.64 mmol/L (500 mg/dL)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Leili Gao, Doctor</last_name>
    <phone>00861088325578</phone>
    <phone_ext>00861088324516</phone_ext>
    <email>plum_jj@sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Linong Ji, Doctor</last_name>
    <phone>00861088325578</phone>
    <phone_ext>00861088324516</phone_ext>
    <email>jiln@bjmu.edu.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Linong Ji</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Linong Ji</last_name>
      <phone>00861088325578</phone>
      <phone_ext>00861088325578</phone_ext>
      <email>plum_jj@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>July 14, 2020</last_update_submitted>
  <last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2020</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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03811548
org study id: 5695-DIA-3001
nct id: NCT03811548
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to assess the effect of Janagliflozin relative to placebo on
      glycated hemoglobin (HbA1c) after 24 weeks of treatment, and to assess the efficacy after 52
      weeks of treatment, overall safety and Population pharmacokinetics.
A multicentre, randomized, double-blind, parallel group, placebo-controlled study(24 weeks
      core period followed by 28 Weeks Extension period), to evaluate the efficacy and safety of
      Janagliflozin (25 mg and 50 mg) compared to placebo in patients diagnosed with T2DM who are
      not achieving an adequate response from diet and exercise to control their diabetes.
      Approximately 390 patients with inadequate glycemic control with diet and exercise will
      receive once-daily double-blind treatment with Janagliflozin 25 mg or 50 mg once daily for 52
      weeks, or 24 weeks of double-blind treatment with placebo followed by 28 weeks of
      single-blind treatment with Janagliflozin 25 mg or 50 mg. During the treatment, if a
      patient's glycemic level remains high despite treatment with study drug and reinforcement
      with diet and exercise, the patient will receive treatment with metformin (rescue therapy)
      consistent with local prescribing information. Study drug will be taken orally once daily.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double Blind
measure: Change in HbA1c From Baseline to Week 24
time frame: Baseline and Week 24
description: To examine whether the mean change in HbA1c from baseline to week 24 with Janagliflozin is superiority (superiority margin of 0.5%) to placebo
measure: Change in HbA1c From Baseline to Week 52
time frame: Baseline and Week 52
description: To compare the mean change in HbA1c from baseline to week 52 between groups
measure: Percentage of Patients With HbA1c <7% at Week 24 (Core period) and week 52
time frame: Baseline, Week 24 and week 52
description: To compare the percentage of patients with HbA1c <7% at week 24 (core period) and week 52 (extension period) between groups
measure: Percentage of Patients With HbA1c <6.5% at Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the percentage of patients with HbA1c <6.5% at week 24 (core period) and Week 52 (extension period) between groups
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in fasting plasma glucose (FPG) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups
measure: Change in 2-hour Post-prandial Glucose From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in 2-hour post-prandial glucose from Baseline to Week 24 (core period) and Week 52 (extension period) between groups
measure: Change in Blood Lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in blood lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups
measure: Change in Blood Pressure (systolic blood pressure and diastolic blood pressure) From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in blood pressure (systolic blood pressure and diastolic blood pressure) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups
measure: Change in Body Weight From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in body weight from Baseline to Week 24 (core period) and Week 52 (extension period) between groups
measure: Change in Fasting C-peptide From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in fasting C-peptide from Baseline to Week 24 (core period) and Week 52 (extension period) between groups.
measure: Change in Insulin Sensitivity From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in insulin sensitivity from Baseline to Week 24 (core period) and Week 52 (extension period) between groups
measure: Change in β-cell Function From Baseline to Week 24 (Core period) and Week 52 (Extension period)
time frame: Baseline, Week 24 and Week 52
description: To compare the mean change in β-cell function from Baseline to Week 24 (core period) and Week 52 (extension period) between groups.
measure: Percentage of Patients Who Have Received Rescue Therapy at Week 24 (Core period) and Week 52 (Extension period)
time frame: Week 24 and Week 52
description: To compare the percentage of patients who have received rescue therapy by Week 24 (core period) and Week 52 (extension period) between groups
measure: Urinary albumin/creatinine ratio (UACR)
time frame: From Baseline to Week 52
description: To evaluate Urinary albumin/creatinine ratio in different group
measure: Occurrence of adverse events
time frame: From Baseline to Week 52
description: To evaluate adverse events in different group
measure: Occurrence of hypoglycaemic episodes
time frame: From Baseline to Week 52
description: To evaluate adverse events in different group
measure: Population pharmacokinetics assessment
time frame: Baseline, Week 2, Week4, Week8, Week24
description: By compare patients' Minimum Plasma Concentration (on week 2, 4, 8, 24)to eveluate Janagliflozin population pharmacokinetics characteristics
arm group label: Janagliflozin 25mg
arm group type: Experimental
description: Each patient will receive 25 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period)
arm group label: Janagliflozin 50mg
arm group type: Experimental
description: Each patient will receive 50 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period)
arm group label: Placebo/Janagliflozin
arm group type: Experimental
description: In the core period, each patient will receive placebo once daily for 24 weeks and will then switch from placebo to 25 mg or 50 mg of Janagliflozin once daily until Week 52.
intervention type: Drug
intervention name: Janagliflozin 25mg
description: Tablets, Oral, 25 mg, Tablets, Oral, 50 mg
arm group label: Janagliflozin 25mg
other name: Placebo 50mg
intervention type: Drug
intervention name: Janagliflozin 50mg
description: Tablets, Oral, 25 mg, Once daily, 52 weeks
arm group label: Janagliflozin 50mg
other name: Placebo 25mg
intervention type: Drug
intervention name: Placebo/Janagliflozin
description: Tablets, Oral, 25 mg, Once daily, 52 weeks
arm group label: Placebo/Janagliflozin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Leili Gao, Doctor
phone: 00861088325578
phone ext: 00861088324516
email: plum_jj@sina.com
last name: Linong Ji, Doctor
phone: 00861088325578
phone ext: 00861088324516
email: jiln@bjmu.edu.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
sharing ipd: Undecided