<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/NCT01729403</url>
  </required_header>
  <id_info>
    <org_study_id>WC28038</org_study_id>
    <nct_id>NCT01729403</nct_id>
  </id_info>
  <brief_title>A Study of The Effect of Aleglitazar on Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus Who Are Inadequately Controlled With Metformin</brief_title>
  <official_title>A Single Centre, Randomized, Double-Blind, Placebo-Controlled, Phase II Study to Assess the Efficacy of Aleglitazar on Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus (T2D) Who Are Inadequately Controlled With Metformin Monotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This single-center, randomized, double-blind, placebo-controlled study will evaluate the&#xD;
      effect of aleglitazar on insulin sensitivity in patients with type 2 diabetes mellitus who&#xD;
      are inadequately controlled on metformin monotherapy. Patients will be randomized to receive&#xD;
      either aleglitazar 150 mcg or placebo orally daily for 16 weeks, in addition to their&#xD;
      existing dose and regimen of metformin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">September 2013</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>Phase 2</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 whole-body insulin sensitivity as assessed by M-value (Insulin-stimulated glucose disposal rate)</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in hepatic insulin sensitivity (basal index of hepatic insulin resistance)</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in parameters of beta cell function (first and second phase insulin secretion)</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HbA1c</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lipid profile</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in mean 24h blood pressure</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hepatic fat content measured by magnetic resonance spectroscopy (MRI)</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fat content/distribution in the abdominal region measured by MRI</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in total body fat content measured by air displacement phlethysmography</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in homeostatic indexes of insulin sensitivity assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-IS)</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in markers of cardiovascular risk (high sensitivity C-reactive protein, adiponectin, free fatty acid)</measure>
    <time_frame>from baseline to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety: Incidence of adverse events</measure>
    <time_frame>22 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Diabetes Mellitus Type 2</condition>
  <arm_group>
    <arm_group_label>Aleglitazar</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>aleglitazar</intervention_name>
    <description>150 mcg orally daily, 16 weeks</description>
    <arm_group_label>Aleglitazar</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin</intervention_name>
    <description>patients will continue on their existing dose and regimen of metformin (but not more than the maximum dose specified in the label)</description>
    <arm_group_label>Aleglitazar</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>orally daily, 16 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients, 30 to 70 years of age inclusive at screening&#xD;
&#xD;
          -  Type 2 diabetes mellitus patients treated with stable metformin therapy for at least&#xD;
             12 weeks prior to screening; metformin dose should not exceed the maximum dose&#xD;
             specified in the label&#xD;
&#xD;
          -  HbA1c &gt;/= 6.5% and &lt;/= 9% at screening and baseline&#xD;
&#xD;
          -  Fasting plasma glucose &lt;/= 13.3 mmol/L (&lt;/= 240 mg/dl) at screening and baseline&#xD;
&#xD;
          -  Body mass index (BMI) &gt;/= 25 at screening; BMI &gt;/= 27 for subjects with HbA1c &lt; 7%&#xD;
&#xD;
          -  Stable weight +/- 5% for at least 12 weeks prior to screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant, intending to become pregnant during the study period,&#xD;
             currently lactating women, or women of child-bearing potential not using highly&#xD;
             effective, medically approved birth control methods&#xD;
&#xD;
          -  Diagnosis or history of type 1 diabetes mellitus, diabetes resulting from pancreatic&#xD;
             injury, or secondary forms of diabetes&#xD;
&#xD;
          -  Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma&#xD;
             within the past 6 months&#xD;
&#xD;
          -  Any previous treatment with a thiazolidinedione or with a dual peroxisome proliferator&#xD;
             activated receptor (PPAR) agonist&#xD;
&#xD;
          -  Any body weight lowering or lipoprotein-modifying therapy (e.g. fibrates) within 12&#xD;
             weeks prior to screening with the exception of stable (&gt;/= 1 month) statin therapy&#xD;
&#xD;
          -  History of bariatric surgery or currently undergoing evaluation for bariatric surgery&#xD;
&#xD;
          -  Prior intolerance to fibrate&#xD;
&#xD;
          -  Treatment with any anti-diabetic medication other than metformin in the last 12 weeks&#xD;
             prior to screening and/or herbal/over-the-counter preparations that may affect&#xD;
             glycemic control within 12 weeks prior to screening&#xD;
&#xD;
          -  Clinically apparent liver disease&#xD;
&#xD;
          -  Positive for hepatitis B, hepatitis C or HIV infection&#xD;
&#xD;
          -  Clinical evidence of anemia&#xD;
&#xD;
          -  Symptomatic congestive heart failure (New York Heart Association Class II-IV) at&#xD;
             screening&#xD;
&#xD;
          -  Myocardial infarction, acute coronary syndrome, or transient ischemic attack/stroke&#xD;
             within 6 months prior to screening&#xD;
&#xD;
          -  Known macular edema at screening or prior to screening visit&#xD;
&#xD;
          -  Uncontrolled hypertension despite stable (for at least 4 weeks) anti-hypertensive&#xD;
             treatment&#xD;
&#xD;
          -  Diagnosed and/or treated malignancy (except for treated cases of basal cell skin&#xD;
             cancer, in situ carcinoma of the cervix or in situ prostate cancer) within the past 5&#xD;
             years&#xD;
&#xD;
          -  Chronic oral or parenteral corticosteroid treatment (&gt; 2 weeks) within 3 months prior&#xD;
             to screening&#xD;
&#xD;
          -  History of active substance abuse (including alcohol) within the past 2 years or&#xD;
             positive test result for drugs of abuse or alcohol prior to first dosing&#xD;
&#xD;
          -  Presence of any absolute or relative contraindication for the conduct of magnetic&#xD;
             resonance imaging (MRI) investigation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Neuss</city>
        <zip>41460</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 14, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <disposition_first_submitted>August 9, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>August 9, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">August 11, 2016</disposition_first_posted>
  <last_update_submitted>November 1, 2016</last_update_submitted>
  <last_update_submitted_qc>November 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 2, 2016</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>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01729403
org study id: WC28038
nct id: NCT01729403
lead sponsor: 
This single-center, randomized, double-blind, placebo-controlled study will evaluate the
      effect of aleglitazar on insulin sensitivity in patients with type 2 diabetes mellitus who
      are inadequately controlled on metformin monotherapy. Patients will be randomized to receive
      either aleglitazar 150 mcg or placebo orally daily for 16 weeks, in addition to their
      existing dose and regimen of metformin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in whole-body insulin sensitivity as assessed by M-value (Insulin-stimulated glucose disposal rate)
time frame: from baseline to Week 16
measure: Change in hepatic insulin sensitivity (basal index of hepatic insulin resistance)
time frame: from baseline to Week 16
measure: Change in parameters of beta cell function (first and second phase insulin secretion)
time frame: from baseline to Week 16
measure: Change in HbA1c
time frame: from baseline to Week 16
measure: Change in lipid profile
time frame: from baseline to Week 16
measure: Change in mean 24h blood pressure
time frame: from baseline to Week 16
measure: Change in hepatic fat content measured by magnetic resonance spectroscopy (MRI)
time frame: from baseline to Week 16
measure: Change in fat content/distribution in the abdominal region measured by MRI
time frame: from baseline to Week 16
measure: Change in total body fat content measured by air displacement phlethysmography
time frame: from baseline to Week 16
measure: Change in homeostatic indexes of insulin sensitivity assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-IS)
time frame: from baseline to Week 16
measure: Change in markers of cardiovascular risk (high sensitivity C-reactive protein, adiponectin, free fatty acid)
time frame: from baseline to Week 16
measure: Safety: Incidence of adverse events
time frame: 22 weeks
arm group label: Aleglitazar
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: aleglitazar
description: 150 mcg orally daily, 16 weeks
arm group label: Aleglitazar
intervention type: Drug
intervention name: metformin
description: patients will continue on their existing dose and regimen of metformin (but not more than the maximum dose specified in the label)
arm group label: Aleglitazar
arm group label: Placebo
intervention type: Drug
intervention name: placebo
description: orally daily, 16 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance
mesh term: Metformin