<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/NCT02974244</url>
  </required_header>
  <id_info>
    <org_study_id>D5551R00008</org_study_id>
    <nct_id>NCT02974244</nct_id>
  </id_info>
  <brief_title>Comparison of the Effectiveness and Tolerability of Exenatide Once-weekly Compared to Basal Insulins</brief_title>
  <official_title>A Cohort Study of the Benefits of Bydureon in Customary Clinical Care in the United States</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>
      Exenatide once weekly (Bydureon) was approved in January 2012 by FDA in USA for the treatment&#xD;
      of type 2 diabetes mellitus. Evidence from clinical trials suggested that Bydureon improves&#xD;
      glucose control with low risk of hypoglycemia. Bydureon does not require a dose titration as&#xD;
      necessary for other glucagon-like peptide-1 agonists, and appears to have other advantages,&#xD;
      such as reducing insulin resistance, reducing weight, and improving blood pressure and lipid&#xD;
      profiles. However, the degree to which these advantages of Bydureon lead to improve outcomes&#xD;
      in customary clinical care is unknown.&#xD;
&#xD;
      The aim of this study is to evaluate the effectiveness and tolerability of Bydureon relative&#xD;
      to basal insulin initiated as first-ever injectable therapeutic regimens used in customary&#xD;
      clinical care. Patients who initiated treatment with Bydureon or basal insulin between July&#xD;
      2011 and March 2015 will be recruited into the study cohorts from Optum's database of&#xD;
      electronic health records. The two treatment cohorts will be matched by propensity score&#xD;
      method.Clinical outcomes of HbA1c, weight, and gastrointestinal symptoms and hypoglycemia are&#xD;
      investigated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: In January 2012, the US Food and Drug Administration approved a once-weekly form&#xD;
      of exenatide, Bydureon, for the treatment of type 2 diabetes mellitus. Evidence from clinical&#xD;
      trials suggested that Bydureon improves glucose control with low risk of hypoglycemia.&#xD;
      Bydureon does not require a dose titration as necessary for other glucagon-like peptide-1&#xD;
      receptor agonists (GLP-1RAs), and appears to have other advantages, such as reducing insulin&#xD;
      resistance, preventing weight gain, and improving blood pressure and lipid profiles. However,&#xD;
      the degree to which these advantages of Bydureon lead to improve outcomes in customary&#xD;
      clinical care is unknown.&#xD;
&#xD;
      Aims: The aim of this study is to evaluate the effectiveness and tolerability of Bydureon&#xD;
      relative to basal insulin initiated as first-ever injectable therapeutic regimens used in&#xD;
      customary clinical care.&#xD;
&#xD;
      The specific study objectives are as follows:&#xD;
&#xD;
        -  To quantify the effectiveness of Bydureon initiation relative to initiation of basal&#xD;
           insulin, on improving:&#xD;
&#xD;
        -  Glycated hemoglobin (HbA1c)&#xD;
&#xD;
        -  Weight (body mass index (BMI))&#xD;
&#xD;
        -  HbA1c simultaneous to reduction in weight&#xD;
&#xD;
        -  Blood pressure and lipid profiles&#xD;
&#xD;
        -  To monitor the tolerability of Bydureon initiation relative to initiation basal insulin,&#xD;
           on the occurrence of :&#xD;
&#xD;
        -  Hypoglycemia&#xD;
&#xD;
        -  Gastrointestinal symptoms (nausea, vomiting, diarrhea, and constipation)&#xD;
&#xD;
        -  Change in the markers for renal disease (estimated glomerular filtration rate (eGFR),&#xD;
           serum creatinine, and albumin/creatinine ratio (ACR), and the stability of liver&#xD;
           function test (AST, ALT) and standard blood counts (white blood cell, red blood cell,&#xD;
           Hematocrit, Hemoglobin, Platelet)&#xD;
&#xD;
        -  To examine these measures of effectiveness and tolerability within potentially&#xD;
           vulnerable subgroups of Bydureon and basal insulin initiators:&#xD;
&#xD;
        -  Type 2 diabetes patients with renal impairment&#xD;
&#xD;
        -  Elderly Type 2 diabetes patients&#xD;
&#xD;
        -  Type 2 diabetes patients who are a minority race&#xD;
&#xD;
        -  Type 2 diabetes patients within strata of HBA1c Design: This retrospective cohort study&#xD;
           will be conducted using Optum's electronic health record data from July 2011 through&#xD;
           March 2015 and identified injectable-naive Type 2 diabetes patients who initiated either&#xD;
           Bydureon or basal insulin during the accrual period, January 2012 and January 2015.&#xD;
           Injectable-naive Type 2 diabetes patients will be identified. Propensity score methods&#xD;
           will be used to match initiators of Bydureon to basal insulin initiators.&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      The study population will be selected from the electronic health recrod data included&#xD;
      patients with Type 2 diabetes who initiated Bydureon or basal insulin. Eligible patients had:&#xD;
&#xD;
        -  Received care for at least 6 months prior to the date of study drug initiation (cohort&#xD;
           entry) with at least one outpatient clinic visit in the 6 months prior to cohort entry&#xD;
           (baseline period);&#xD;
&#xD;
        -  At least one diagnosis of type 2 diabetes (ICD-9 250.X0 or 250.X2) prior to and&#xD;
           including the date of the qualifying drug initiation, no prior diagnosis (inclusive of&#xD;
           the index date) of type 1 diabetes mellitus (250.X1 or 250.X3), and no diagnosis of&#xD;
           gestational diabetes within the previous 6 months (inclusive of the index date); and&#xD;
&#xD;
        -  No evidence of prior injectable antidiabetic treatment, specifically no dispensing of&#xD;
           GLP-1RA or any insulin drug during the 6-month baseline period. Outcomes and Analysis:&#xD;
           To measure the effectiveness of Bydureon relative to basal insulin are changes in HbA1c&#xD;
           and body weight, as well as changes in HbA1c and simultaneous reduction in weight.&#xD;
           Changes in BMI, lipid profiles, and blood pressure will be examined. These variables are&#xD;
           part of the clinical and laboratory data in the electronic health records. Each outcome&#xD;
           will be evaluated for completeness, multiply imputed, and reported across standardized&#xD;
           time intervals. HbA1c, weight and BMI are summarized in baseline and quarterly (3-month&#xD;
           intervals) in the first year following drug initiation. Lipid measurements and blood&#xD;
           pressure are summarized in baseline and bi-annually (6-month intervals) in the first&#xD;
           year following drug initiation.&#xD;
&#xD;
      To assess drug tolerability, the incidence of hypoglycemia, and gastrointestinal symptoms&#xD;
      (nausea, vomiting, diarrhea, and constipation) will be assessed. These outcomes are&#xD;
      ascertained using an ICD-9 algorithm applied to the structured fields and by extracting&#xD;
      mentions of hypoglycemia using a natural language processing (NLP) algorithm developed by&#xD;
      Optum and applied to the free text clinical notes available in the data. In addition the&#xD;
      stability of renal function evaluated by change in eGFR, or albumin/creatinine ratio (ACR);&#xD;
      the change in serum hepatic enzymes [aspartate aminotransferase (AST), alanine&#xD;
      aminotransferase (ALT)], and hematologic measures [red blood cells counts (RBC), white blood&#xD;
      cell counts (WBC), platelets (PLT), hemoglobin (Hgb) and hematocrit (Hct) will be evaluated.&#xD;
      Each of these laboratory values will be evaluated for completeness, multiply imputed, and&#xD;
      reported across standardized time intervals. eGFR and ACR will be summarized in baseline and&#xD;
      quarterly (3-month intervals) in the first year following drug initiation. Hepatic enzymes&#xD;
      and hematologic measures are summarized in baseline and semi-annually (6-month intervals) in&#xD;
      the first year following drug initiation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 28, 2014</start_date>
  <completion_date type="Actual">October 28, 2014</completion_date>
  <primary_completion_date type="Actual">October 28, 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes from baseline in HbA1c (%)</measure>
    <time_frame>one year post-index</time_frame>
    <description>To evaluate changes in HbA1c from baseline one year after starting treatment with exenatide once weekly and basal insulin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline in weight (kg)</measure>
    <time_frame>one year post-index</time_frame>
    <description>To evaluate changes in weight (kg) from baseline one year after starting treatment with exenatide once weekly and basal insulin</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of hypoglycemia</measure>
    <time_frame>one year post-index</time_frame>
    <description>to evaluate frequency of hypoglycemia in association with initiation of therapy with exenatide once weekly and basal insulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of nausea</measure>
    <time_frame>One year post-index</time_frame>
    <description>to evaluate frequency of nausea in association with initiation of therapy with exenatide once weekly and basal insulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of vomiting</measure>
    <time_frame>one year post-index</time_frame>
    <description>to evaluate frequency of vomiting in association with initiation of therapy with exenatide once weekly and basal insulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of diarrhea and constipation</measure>
    <time_frame>One year post-index</time_frame>
    <description>to evaluate frequency of diarrhea and constipation in association with initiation of therapy with exenatide once weekly and basal insulin</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">7000</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>exenatide once weekly</arm_group_label>
    <description>type 2 diabetes who initiated exenatide once weekly treatment in the index period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>basal insulin</arm_group_label>
    <description>type 2 diabetes patients who initiated basal insulin treatment in the index period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>exenatide once weekly</intervention_name>
    <description>exenatide treatment in the customary clinical care in the USA</description>
    <arm_group_label>exenatide once weekly</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>basal insulin</intervention_name>
    <description>basal insulin treatment in the customary clinical care in USA</description>
    <arm_group_label>basal insulin</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This cohort study compares injectable-naive exenatide once-weekly and basal insulin&#xD;
        initiators. The study cohorts were drawn from an Optum's Electronic Health Records database&#xD;
        that integrates records from many medical groups and hospitals in the United States&#xD;
        representing over 25,000 physicians and over 25 million patients in ordinary clinical&#xD;
        practice. The Electronic Health Records captures clinical, operational, and financial&#xD;
        information that physicians record at the time of care. This information includes&#xD;
        diagnoses, procedures, medications (prescribed and administered), clinical measures&#xD;
        (biometric and laboratory values), and clinical notes (e.g., physician, pathology, and&#xD;
        radiology notes).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years old;&#xD;
&#xD;
          -  had received care documented in Electronic Health Records (including at least one&#xD;
             out-patient provider visit) for a minimum of 6-months prior index date;&#xD;
&#xD;
          -  had at least one diagnosis of type 2 diabetes by The International Classification of&#xD;
             Diseases, Ninth Revision, Clinical Modification (ICD-9-CM: 250.X0 or 250.X2) prior to&#xD;
             and including the date of the study drug initiation, with no prior diagnosis of type1&#xD;
             diabetes (ICD-9-CM: 250.X1 or 250.X3), or gestational diabetes within the 6-months&#xD;
             prior to index date;&#xD;
&#xD;
          -  No evidence of prior injectable antidiabetic treatment, specifically no dispensing of&#xD;
             a GLP-1RA or any insulin during the 6-months baseline period prior to study drug&#xD;
             initiation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior diagnosis of type1 diabetes (ICD-9-CM: 250.X1 or 250.X3), or gestational&#xD;
             diabetes within the 6-months prior to index date;&#xD;
&#xD;
          -  Prior dispensing of a GLP-1RA or any insulin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anita M Loughlin, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Optum, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Optum Epidemiology</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=4433&amp;filename=D5551R00008_Poster_ADA2016.pdf</url>
    <description>CSR Synopsis</description>
  </link>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2016</study_first_posted>
  <last_update_submitted>March 28, 2017</last_update_submitted>
  <last_update_submitted_qc>March 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Type 2 diabetes</keyword>
  <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>Exenatide</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/NCT02974244
org study id: D5551R00008
nct id: NCT02974244
lead sponsor: 
has dmc: No
Exenatide once weekly (Bydureon) was approved in January 2012 by FDA in USA for the treatment
      of type 2 diabetes mellitus. Evidence from clinical trials suggested that Bydureon improves
      glucose control with low risk of hypoglycemia. Bydureon does not require a dose titration as
      necessary for other glucagon-like peptide-1 agonists, and appears to have other advantages,
      such as reducing insulin resistance, reducing weight, and improving blood pressure and lipid
      profiles. However, the degree to which these advantages of Bydureon lead to improve outcomes
      in customary clinical care is unknown.

      The aim of this study is to evaluate the effectiveness and tolerability of Bydureon relative
      to basal insulin initiated as first-ever injectable therapeutic regimens used in customary
      clinical care. Patients who initiated treatment with Bydureon or basal insulin between July
      2011 and March 2015 will be recruited into the study cohorts from Optum's database of
      electronic health records. The two treatment cohorts will be matched by propensity score
      method.Clinical outcomes of HbA1c, weight, and gastrointestinal symptoms and hypoglycemia are
      investigated.
Background: In January 2012, the US Food and Drug Administration approved a once-weekly form
      of exenatide, Bydureon, for the treatment of type 2 diabetes mellitus. Evidence from clinical
      trials suggested that Bydureon improves glucose control with low risk of hypoglycemia.
      Bydureon does not require a dose titration as necessary for other glucagon-like peptide-1
      receptor agonists (GLP-1RAs), and appears to have other advantages, such as reducing insulin
      resistance, preventing weight gain, and improving blood pressure and lipid profiles. However,
      the degree to which these advantages of Bydureon lead to improve outcomes in customary
      clinical care is unknown.

      Aims: The aim of this study is to evaluate the effectiveness and tolerability of Bydureon
      relative to basal insulin initiated as first-ever injectable therapeutic regimens used in
      customary clinical care.

      The specific study objectives are as follows:

        -  To quantify the effectiveness of Bydureon initiation relative to initiation of basal
           insulin, on improving:

        -  Glycated hemoglobin (HbA1c)

        -  Weight (body mass index (BMI))

        -  HbA1c simultaneous to reduction in weight

        -  Blood pressure and lipid profiles

        -  To monitor the tolerability of Bydureon initiation relative to initiation basal insulin,
           on the occurrence of :

        -  Hypoglycemia

        -  Gastrointestinal symptoms (nausea, vomiting, diarrhea, and constipation)

        -  Change in the markers for renal disease (estimated glomerular filtration rate (eGFR),
           serum creatinine, and albumin/creatinine ratio (ACR), and the stability of liver
           function test (AST, ALT) and standard blood counts (white blood cell, red blood cell,
           Hematocrit, Hemoglobin, Platelet)

        -  To examine these measures of effectiveness and tolerability within potentially
           vulnerable subgroups of Bydureon and basal insulin initiators:

        -  Type 2 diabetes patients with renal impairment

        -  Elderly Type 2 diabetes patients

        -  Type 2 diabetes patients who are a minority race

        -  Type 2 diabetes patients within strata of HBA1c Design: This retrospective cohort study
           will be conducted using Optum's electronic health record data from July 2011 through
           March 2015 and identified injectable-naive Type 2 diabetes patients who initiated either
           Bydureon or basal insulin during the accrual period, January 2012 and January 2015.
           Injectable-naive Type 2 diabetes patients will be identified. Propensity score methods
           will be used to match initiators of Bydureon to basal insulin initiators.

      Study Population:

      The study population will be selected from the electronic health recrod data included
      patients with Type 2 diabetes who initiated Bydureon or basal insulin. Eligible patients had:

        -  Received care for at least 6 months prior to the date of study drug initiation (cohort
           entry) with at least one outpatient clinic visit in the 6 months prior to cohort entry
           (baseline period);

        -  At least one diagnosis of type 2 diabetes (ICD-9 250.X0 or 250.X2) prior to and
           including the date of the qualifying drug initiation, no prior diagnosis (inclusive of
           the index date) of type 1 diabetes mellitus (250.X1 or 250.X3), and no diagnosis of
           gestational diabetes within the previous 6 months (inclusive of the index date); and

        -  No evidence of prior injectable antidiabetic treatment, specifically no dispensing of
           GLP-1RA or any insulin drug during the 6-month baseline period. Outcomes and Analysis:
           To measure the effectiveness of Bydureon relative to basal insulin are changes in HbA1c
           and body weight, as well as changes in HbA1c and simultaneous reduction in weight.
           Changes in BMI, lipid profiles, and blood pressure will be examined. These variables are
           part of the clinical and laboratory data in the electronic health records. Each outcome
           will be evaluated for completeness, multiply imputed, and reported across standardized
           time intervals. HbA1c, weight and BMI are summarized in baseline and quarterly (3-month
           intervals) in the first year following drug initiation. Lipid measurements and blood
           pressure are summarized in baseline and bi-annually (6-month intervals) in the first
           year following drug initiation.

      To assess drug tolerability, the incidence of hypoglycemia, and gastrointestinal symptoms
      (nausea, vomiting, diarrhea, and constipation) will be assessed. These outcomes are
      ascertained using an ICD-9 algorithm applied to the structured fields and by extracting
      mentions of hypoglycemia using a natural language processing (NLP) algorithm developed by
      Optum and applied to the free text clinical notes available in the data. In addition the
      stability of renal function evaluated by change in eGFR, or albumin/creatinine ratio (ACR);
      the change in serum hepatic enzymes [aspartate aminotransferase (AST), alanine
      aminotransferase (ALT)], and hematologic measures [red blood cells counts (RBC), white blood
      cell counts (WBC), platelets (PLT), hemoglobin (Hgb) and hematocrit (Hct) will be evaluated.
      Each of these laboratory values will be evaluated for completeness, multiply imputed, and
      reported across standardized time intervals. eGFR and ACR will be summarized in baseline and
      quarterly (3-month intervals) in the first year following drug initiation. Hepatic enzymes
      and hematologic measures are summarized in baseline and semi-annually (6-month intervals) in
      the first year following drug initiation.
observational model: Cohort
time perspective: Retrospective
measure: Changes from baseline in HbA1c (%)
time frame: one year post-index
description: To evaluate changes in HbA1c from baseline one year after starting treatment with exenatide once weekly and basal insulin
measure: Changes from baseline in weight (kg)
time frame: one year post-index
description: To evaluate changes in weight (kg) from baseline one year after starting treatment with exenatide once weekly and basal insulin
measure: Frequency of hypoglycemia
time frame: one year post-index
description: to evaluate frequency of hypoglycemia in association with initiation of therapy with exenatide once weekly and basal insulin
measure: Frequency of nausea
time frame: One year post-index
description: to evaluate frequency of nausea in association with initiation of therapy with exenatide once weekly and basal insulin
measure: Frequency of vomiting
time frame: one year post-index
description: to evaluate frequency of vomiting in association with initiation of therapy with exenatide once weekly and basal insulin
measure: Frequency of diarrhea and constipation
time frame: One year post-index
description: to evaluate frequency of diarrhea and constipation in association with initiation of therapy with exenatide once weekly and basal insulin
arm group label: exenatide once weekly
description: type 2 diabetes who initiated exenatide once weekly treatment in the index period
arm group label: basal insulin
description: type 2 diabetes patients who initiated basal insulin treatment in the index period
intervention type: Drug
intervention name: exenatide once weekly
description: exenatide treatment in the customary clinical care in the USA
arm group label: exenatide once weekly
intervention type: Drug
intervention name: basal insulin
description: basal insulin treatment in the customary clinical care in USA
arm group label: basal insulin
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Anita M Loughlin, Ph.D
role: Principal Investigator
affiliation: Optum, Inc.
facility: 
country: United States
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4433&filename=D5551R00008_Poster_ADA2016.pdf
description: CSR Synopsis
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
mesh term: Exenatide