<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/NCT02252224</url>
  </required_header>
  <id_info>
    <org_study_id>D1690L00018</org_study_id>
    <nct_id>NCT02252224</nct_id>
  </id_info>
  <brief_title>Forxiga (Dapagliflozin) Regulatory Postmarketing Surveillance</brief_title>
  <official_title>Post-Marketing Surveillance to Evaluate the Safety and Efficacy of Forxiga in Patients With Type 2 Diabetes in Korea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This surveillance is a postmarketing commitment following the marketing authorization for&#xD;
      Forxiga(dapagliflozin) in accordance with Standards on Re-examination of New Drugs, notified&#xD;
      by the MFDS under Article 32, Paragraph 1 and Article 37, Paragraph 3 of Pharmaceutical&#xD;
      Affairs Law. MFDS requires that at least 3,000 patients who can be evaluated for safety&#xD;
      assessment should be collected within 6 years from 26 Nov 2013 to 25 Nov 2019.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Protocol Title: Forxiga (dapagliflozin) Regulatory Postmarketing Surveillance&#xD;
&#xD;
      Department: Korea Medical&#xD;
&#xD;
      Objective(s): The primary objective of this study is to examine the safety profiles of&#xD;
      Forxiga in Korean patients with T2DM.&#xD;
&#xD;
      The secondary objective of this study is to examine the effectiveness profiles of Forxiga in&#xD;
      Korean patient with T2DM.&#xD;
&#xD;
      The exploratory objective of this study is to identify factors that might be associated with&#xD;
      the safety and effectiveness profiles of Forxiga in Korean patient with T2DM.&#xD;
&#xD;
      Study Design: This is a local, prospective, noninterventional, regulatory postmarketing&#xD;
      surveillance study. Adult patients with type 2 diabetes mellitus who are initiating Forxiga&#xD;
      as indicated by the Ministry of Food and Drug Safety (MFDS) will be included. Patients will&#xD;
      be followed for a minimum of 12 weeks or a minimum 24 weeks. Patients will be treated as part&#xD;
      of routine practice at Korean healthcare centers by accredited physicians. In this study,&#xD;
      patients will receive 10 mg or 5 mg of Forxiga in conjunction with diet and exercise&#xD;
      modifications for the treatment of T2DM.&#xD;
&#xD;
      Study Population: Physicians should enroll adult patients who are diagnosed with T2DM and who&#xD;
      initiate treatment with 10 mg of Forxiga, or 5 mg of Forxiga in patients with severe hepatic&#xD;
      impairment as a starting dose, for the first time.&#xD;
&#xD;
      Data Collection Methods: and Astra-Zeneca will select medical institutions including relevant&#xD;
      departments, such as internal medicine and family medicine, of university hospitals, general&#xD;
      hospitals and clinics where the surveillance drug is mainly prescribed and where staff can&#xD;
      sufficiently fulfill the objectives of the surveillance and request for surveillance after&#xD;
      signing a written contract. Patients' medical records will be data sources in this study.&#xD;
      Only if the laboratory test is done as part of standard of care practice and the data are&#xD;
      available will the data be collected for this study.&#xD;
&#xD;
      Data Analyses: Statistical analyses will be of explorative and descriptive nature. All&#xD;
      analyses will be performed for the total study population who will consist of all patients&#xD;
      taking at least one dose of Forxiga. For the safety assessment, occurrences of adverse events&#xD;
      (AEs), serious adverse events, adverse drug reactions (ADR), and unexpected adverse drug&#xD;
      reactions will be calculated. Severity, actions taken to the surveillance drug, outcome, and&#xD;
      causal relationship of AE to the study drug will be analyzed. At the time of the regular&#xD;
      reporting and the final reporting, the event count, incidence proportion (that is, the number&#xD;
      of patients with any events divided by the number of patients) and incidence rate (number of&#xD;
      patients with any events divided by the duration of time patients are followed up in the&#xD;
      study) of all the adverse events surveyed during the re-examination period will be&#xD;
      summarized, and 95% confidence interval will be presented. Changes in Hemoglobin A1c(HbA1c),&#xD;
      Fasting plasma glucose(FPG), and Post-prandial glucose-2 hour(2-hr PPG) before and after&#xD;
      administration of Forxiga will be analyzed. At the time of the regular reporting and the&#xD;
      final reporting, the event count and effectiveness rate of improvement of lab result (HbA1c,&#xD;
      FPG, and PPG), surveyed during the re-examination period will be summarized, and 95%&#xD;
      confidence interval will be presented. In order to explore the factors that might influence&#xD;
      safety and effectiveness profiles, the cumulative incidence proportion of adverse events and&#xD;
      effectiveness rate will be analyzed by patients' background characteristics Sample&#xD;
      Size/Power: In accordance with the guidelines provided by the MFDS, at least 3,000 patients&#xD;
      will be enrolled. For the overall study population of approximately 3000 patients, the&#xD;
      incidence proportion of infrequent adverse events(for example, an incidence proportion of&#xD;
      0.1%) can be estimated with a 95% CI of (0.02, 0.29) (n=3 patients with events).&#xD;
&#xD;
      Limitations/Strengths: The surveillance, with characteristics of a noninterventional,&#xD;
      observation study, has no control group and will follow patients in usual clinical practice.&#xD;
      Given these conditions, the types of safety and effectiveness data available for collection&#xD;
      may be limited compared with other noninterventional clinical trials. This surveillance study&#xD;
      will generate results from a wider range of data than those previously derived from the more&#xD;
      limited clinical trial setting and will allow for longer follow up among a more varied&#xD;
      patient population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 23, 2014</start_date>
  <completion_date type="Actual">November 30, 2016</completion_date>
  <primary_completion_date type="Actual">November 30, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The number and incidence rate of adverse events and serious adverse event including unexpected adverse drug reactions</measure>
    <time_frame>Adverse event will be collected from baseline(Day1) to 3 days after 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks))</time_frame>
    <description>All patients should be evaluated if they received at least one dose of the study medication. Safety will be evaluated through: • Incidence of serious adverse events • Incidence of unexpected adverse drug reactions • Identification of AE profile in usual practice • Report of AE in routine office visit or through phone or e-mail follow up • Incidence of nonserious adverse events All AEs that occurred on the surveillance drug treatment or within 3 days after the end of the treatment, whether or not related to the drug, will be recorded. The safety assessment should include all undesirable changes of medical findings (including a clinical test finding) noted during medical visits as needed according to local practice guidelines and all AEs associated with surveillance drug administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in HbA1c before and after administration of Forxiga</measure>
    <time_frame>Baseline, 12 weeks (maximum 16 weeks), 24 weeks (maximum 30 weeks) in case of long-term surveillance</time_frame>
    <description>Medical records and laboratory test results will be used to determine effectiveness as judged by the investigator. Changes from baseline to at least 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks) in case of long-term surveillance will be assessed for the following outcome measure (if assessed during routine clinical practice): HbA1c (Hemoglobin A1c)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in FPG before and after administration of Forxiga</measure>
    <time_frame>Baseline, 12 weeks (maximum 16 weeks), 24 weeks (maximum 30 weeks) in case of long-term surveillance</time_frame>
    <description>Medical records and laboratory test results will be used to determine effectiveness as judged by the investigator. Changes from baseline to at least 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks) in case of long-term surveillance will be assessed for the following outcome measure (if assessed during routine clinical practice): FPG (fasting plasma glucose)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in 2-hr PPG before and after administration of Forxiga</measure>
    <time_frame>Baseline, 12 weeks (maximum 16 weeks), 24 weeks (maximum 30 weeks) in case of long-term surveillance</time_frame>
    <description>Medical records and laboratory test results will be used to determine effectiveness as judged by the investigator. Changes from baseline to at least 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks) in case of long-term surveillance will be assessed for the following outcome measure (if assessed during routine clinical practice): 2-hr PPG (2-hr post-prandial glucose)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">3123</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>T2DM patients treated with Forxiga</arm_group_label>
    <description>Korean patients who are at least 18 years old, diagnosed with type2 diabetes and treated with Forxiga according to the approved lable</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients with type 2 diabetes mellitus who are initiating Forxiga&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 18 years and older&#xD;
&#xD;
          -  Patients with T2DM eligible for treatment with Forxiga as indicated in the locally&#xD;
             approved prescribing information&#xD;
&#xD;
          -  Patients with evidence of a personally signed and dated informed consent document&#xD;
             indicating that the patient (or a legally acceptable representative) has been informed&#xD;
             of all pertinent aspects of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients treated with Forxiga outside of the locally approved label in Korea&#xD;
&#xD;
          -  Patients with contraindications for the use of Forxiga (as described in the Korean&#xD;
             product label)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>A Ri Kim</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca Korea - Medical Affairs</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bucheon-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Busan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Daejeon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jeonju-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wonju-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>March 13, 2020</last_update_submitted>
  <last_update_submitted_qc>March 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 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>
  <!-- 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/NCT02252224
org study id: D1690L00018
nct id: NCT02252224
lead sponsor: 
has dmc: No
This surveillance is a postmarketing commitment following the marketing authorization for
      Forxiga(dapagliflozin) in accordance with Standards on Re-examination of New Drugs, notified
      by the MFDS under Article 32, Paragraph 1 and Article 37, Paragraph 3 of Pharmaceutical
      Affairs Law. MFDS requires that at least 3,000 patients who can be evaluated for safety
      assessment should be collected within 6 years from 26 Nov 2013 to 25 Nov 2019.
Protocol Title: Forxiga (dapagliflozin) Regulatory Postmarketing Surveillance

      Department: Korea Medical

      Objective(s): The primary objective of this study is to examine the safety profiles of
      Forxiga in Korean patients with T2DM.

      The secondary objective of this study is to examine the effectiveness profiles of Forxiga in
      Korean patient with T2DM.

      The exploratory objective of this study is to identify factors that might be associated with
      the safety and effectiveness profiles of Forxiga in Korean patient with T2DM.

      Study Design: This is a local, prospective, noninterventional, regulatory postmarketing
      surveillance study. Adult patients with type 2 diabetes mellitus who are initiating Forxiga
      as indicated by the Ministry of Food and Drug Safety (MFDS) will be included. Patients will
      be followed for a minimum of 12 weeks or a minimum 24 weeks. Patients will be treated as part
      of routine practice at Korean healthcare centers by accredited physicians. In this study,
      patients will receive 10 mg or 5 mg of Forxiga in conjunction with diet and exercise
      modifications for the treatment of T2DM.

      Study Population: Physicians should enroll adult patients who are diagnosed with T2DM and who
      initiate treatment with 10 mg of Forxiga, or 5 mg of Forxiga in patients with severe hepatic
      impairment as a starting dose, for the first time.

      Data Collection Methods: and Astra-Zeneca will select medical institutions including relevant
      departments, such as internal medicine and family medicine, of university hospitals, general
      hospitals and clinics where the surveillance drug is mainly prescribed and where staff can
      sufficiently fulfill the objectives of the surveillance and request for surveillance after
      signing a written contract. Patients' medical records will be data sources in this study.
      Only if the laboratory test is done as part of standard of care practice and the data are
      available will the data be collected for this study.

      Data Analyses: Statistical analyses will be of explorative and descriptive nature. All
      analyses will be performed for the total study population who will consist of all patients
      taking at least one dose of Forxiga. For the safety assessment, occurrences of adverse events
      (AEs), serious adverse events, adverse drug reactions (ADR), and unexpected adverse drug
      reactions will be calculated. Severity, actions taken to the surveillance drug, outcome, and
      causal relationship of AE to the study drug will be analyzed. At the time of the regular
      reporting and the final reporting, the event count, incidence proportion (that is, the number
      of patients with any events divided by the number of patients) and incidence rate (number of
      patients with any events divided by the duration of time patients are followed up in the
      study) of all the adverse events surveyed during the re-examination period will be
      summarized, and 95% confidence interval will be presented. Changes in Hemoglobin A1c(HbA1c),
      Fasting plasma glucose(FPG), and Post-prandial glucose-2 hour(2-hr PPG) before and after
      administration of Forxiga will be analyzed. At the time of the regular reporting and the
      final reporting, the event count and effectiveness rate of improvement of lab result (HbA1c,
      FPG, and PPG), surveyed during the re-examination period will be summarized, and 95%
      confidence interval will be presented. In order to explore the factors that might influence
      safety and effectiveness profiles, the cumulative incidence proportion of adverse events and
      effectiveness rate will be analyzed by patients' background characteristics Sample
      Size/Power: In accordance with the guidelines provided by the MFDS, at least 3,000 patients
      will be enrolled. For the overall study population of approximately 3000 patients, the
      incidence proportion of infrequent adverse events(for example, an incidence proportion of
      0.1%) can be estimated with a 95% CI of (0.02, 0.29) (n=3 patients with events).

      Limitations/Strengths: The surveillance, with characteristics of a noninterventional,
      observation study, has no control group and will follow patients in usual clinical practice.
      Given these conditions, the types of safety and effectiveness data available for collection
      may be limited compared with other noninterventional clinical trials. This surveillance study
      will generate results from a wider range of data than those previously derived from the more
      limited clinical trial setting and will allow for longer follow up among a more varied
      patient population.
observational model: Case-Only
time perspective: Prospective
measure: The number and incidence rate of adverse events and serious adverse event including unexpected adverse drug reactions
time frame: Adverse event will be collected from baseline(Day1) to 3 days after 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks))
description: All patients should be evaluated if they received at least one dose of the study medication. Safety will be evaluated through: • Incidence of serious adverse events • Incidence of unexpected adverse drug reactions • Identification of AE profile in usual practice • Report of AE in routine office visit or through phone or e-mail follow up • Incidence of nonserious adverse events All AEs that occurred on the surveillance drug treatment or within 3 days after the end of the treatment, whether or not related to the drug, will be recorded. The safety assessment should include all undesirable changes of medical findings (including a clinical test finding) noted during medical visits as needed according to local practice guidelines and all AEs associated with surveillance drug administration.
measure: Changes in HbA1c before and after administration of Forxiga
time frame: Baseline, 12 weeks (maximum 16 weeks), 24 weeks (maximum 30 weeks) in case of long-term surveillance
description: Medical records and laboratory test results will be used to determine effectiveness as judged by the investigator. Changes from baseline to at least 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks) in case of long-term surveillance will be assessed for the following outcome measure (if assessed during routine clinical practice): HbA1c (Hemoglobin A1c)
measure: Changes in FPG before and after administration of Forxiga
time frame: Baseline, 12 weeks (maximum 16 weeks), 24 weeks (maximum 30 weeks) in case of long-term surveillance
description: Medical records and laboratory test results will be used to determine effectiveness as judged by the investigator. Changes from baseline to at least 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks) in case of long-term surveillance will be assessed for the following outcome measure (if assessed during routine clinical practice): FPG (fasting plasma glucose)
measure: Changes in 2-hr PPG before and after administration of Forxiga
time frame: Baseline, 12 weeks (maximum 16 weeks), 24 weeks (maximum 30 weeks) in case of long-term surveillance
description: Medical records and laboratory test results will be used to determine effectiveness as judged by the investigator. Changes from baseline to at least 12 weeks (maximum 16 weeks) or 24 weeks (maximum 30 weeks) in case of long-term surveillance will be assessed for the following outcome measure (if assessed during routine clinical practice): 2-hr PPG (2-hr post-prandial glucose)
arm group label: T2DM patients treated with Forxiga
description: Korean patients who are at least 18 years old, diagnosed with type2 diabetes and treated with Forxiga according to the approved lable
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: A Ri Kim
role: Study Director
affiliation: AstraZeneca Korea - Medical Affairs
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2