<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/NCT01661946</url>
  </required_header>
  <id_info>
    <org_study_id>QueensU</org_study_id>
    <nct_id>NCT01661946</nct_id>
  </id_info>
  <brief_title>Bloodstream Absorption of Avastin and Lucentis After Injection Into the Eye</brief_title>
  <official_title>Systemic Absorption of Bevacizumab and Ranibizumab in Humans Treated for Diabetic Macular Edema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen's University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Physicians' Services Incorporated Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Queen's University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently, two similar medications are available for injection into the eye to treat a&#xD;
      variety of eye diseases. These medications are called ranibizumab (Lucentis) and bevacizumab&#xD;
      (Avastin). They both have a similar mechanism of action and work equally well, however only&#xD;
      ranibizumab was designed for use in the eye. It is significantly more expensive per injection&#xD;
      than bevacizumab (by a factor of roughly 40x).&#xD;
&#xD;
      In published studies trends have been noted towards an increased rate of systemic side&#xD;
      effects such as heart attacks and strokes. This is presumably due to absorption of the&#xD;
      drug(s) from the eye into the bloodstream, however this has never been shown before. The&#xD;
      purpose of the investigators study was to compare the bloodstream levels of bevacizumab and&#xD;
      ranibizumab at various time points after injection into the eye. This required the creation&#xD;
      of a sophisticated assay to measure blood levels of the drugs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      see above&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">July 2013</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Concentration (Cmax) of Anti-VEGF Antibody</measure>
    <time_frame>1 month</time_frame>
    <description>The serum concentrations of anti-VEGF antibody (bevacizumab or ranibizumab) will be measured pre-injection as well as at various time points after injection (1 day, 1 week, 2 weeks, 1 month). These time points are selected based on previously completed animal studies. The Cmax will be compared between bevacizumab and ranibizumab.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>Ranibizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>intravitreal injection of 0.5mg ranibizumab in usual fashion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bevacizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>intravitreal injection of 1.25mg bevacizumab in usual fashion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab is an off-label but cheaper treatment for diabetic macular edema.</description>
    <arm_group_label>Bevacizumab</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranibizumab</intervention_name>
    <description>Ranibizumab is a vascular endothelial growth factor inhibitor designed for ocular use</description>
    <arm_group_label>Ranibizumab</arm_group_label>
    <other_name>Lucentis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients in whom anti-vascular endothelial growth factor (VEGF) therapy is indicated&#xD;
             for the treatment of diabetic macular edema&#xD;
&#xD;
          -  able to return for extra clinic visits according to study schedule&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  active malignancy&#xD;
&#xD;
          -  previous retinal laser treatment&#xD;
&#xD;
          -  previous anti-VEGF therapy&#xD;
&#xD;
          -  previous vitrectomy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sanjay Sharma, MD MBA MSc FRCSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Ophthalmology, Queen's University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hotel Dieu Hospital</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 5G2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 2, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <results_first_submitted>February 26, 2019</results_first_submitted>
  <results_first_submitted_qc>February 26, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 31, 2019</results_first_posted>
  <last_update_submitted>February 26, 2019</last_update_submitted>
  <last_update_submitted_qc>February 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Queen's University</investigator_affiliation>
    <investigator_full_name>Dr. Sanjay Sharma</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>vascular endothelial growth factor</keyword>
  <keyword>macular edema</keyword>
  <keyword>diabetic retinopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Ranibizumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ranibizumab</title>
          <description>intravitreal injection of 0.5mg ranibizumab in usual fashion&#xD;
Ranibizumab: Ranibizumab is a vascular endothelial growth factor inhibitor designed for ocular use</description>
        </group>
        <group group_id="P2">
          <title>Bevacizumab</title>
          <description>intravitreal injection of 1.25mg bevacizumab in usual fashion&#xD;
Bevacizumab: Bevacizumab is an off-label but cheaper treatment for diabetic macular edema.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bevacizumab</title>
        </group>
        <group group_id="B2">
          <title>Ranibizumab</title>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.5" lower_limit="50" upper_limit="73"/>
                    <measurement group_id="B2" value="67.9" lower_limit="55" upper_limit="85"/>
                    <measurement group_id="B3" value="65.2" lower_limit="50" upper_limit="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Concentration (Cmax) of Anti-VEGF Antibody</title>
        <description>The serum concentrations of anti-VEGF antibody (bevacizumab or ranibizumab) will be measured pre-injection as well as at various time points after injection (1 day, 1 week, 2 weeks, 1 month). These time points are selected based on previously completed animal studies. The Cmax will be compared between bevacizumab and ranibizumab.</description>
        <time_frame>1 month</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab</title>
            <description>intravitreal injection of 0.5mg ranibizumab in usual fashion&#xD;
Ranibizumab: Ranibizumab is a vascular endothelial growth factor inhibitor designed for ocular use</description>
          </group>
          <group group_id="O2">
            <title>Bevacizumab</title>
            <description>intravitreal injection of 1.25mg bevacizumab in usual fashion&#xD;
Bevacizumab: Bevacizumab is an off-label but cheaper treatment for diabetic macular edema.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Concentration (Cmax) of Anti-VEGF Antibody</title>
          <description>The serum concentrations of anti-VEGF antibody (bevacizumab or ranibizumab) will be measured pre-injection as well as at various time points after injection (1 day, 1 week, 2 weeks, 1 month). These time points are selected based on previously completed animal studies. The Cmax will be compared between bevacizumab and ranibizumab.</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.22" spread="7.59"/>
                    <measurement group_id="O2" value="9.56" spread="2.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Ranibizumab</title>
          <description>intravitreal injection of 0.5mg ranibizumab in usual fashion&#xD;
Ranibizumab: Ranibizumab is a vascular endothelial growth factor inhibitor designed for ocular use</description>
        </group>
        <group group_id="E2">
          <title>Bevacizumab</title>
          <description>intravitreal injection of 1.25mg bevacizumab in usual fashion&#xD;
Bevacizumab: Bevacizumab is an off-label but cheaper treatment for diabetic macular edema.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Sanjay Sharma</name_or_title>
      <organization>Queen's University Department of Ophthalmology</organization>
      <phone>613-544-3400 ext 2227</phone>
      <email>sanjay_sharma60@hotmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01661946
org study id: QueensU
nct id: NCT01661946
lead sponsor: 
collaborator: 
has dmc: No
Currently, two similar medications are available for injection into the eye to treat a
      variety of eye diseases. These medications are called ranibizumab (Lucentis) and bevacizumab
      (Avastin). They both have a similar mechanism of action and work equally well, however only
      ranibizumab was designed for use in the eye. It is significantly more expensive per injection
      than bevacizumab (by a factor of roughly 40x).

      In published studies trends have been noted towards an increased rate of systemic side
      effects such as heart attacks and strokes. This is presumably due to absorption of the
      drug(s) from the eye into the bloodstream, however this has never been shown before. The
      purpose of the investigators study was to compare the bloodstream levels of bevacizumab and
      ranibizumab at various time points after injection into the eye. This required the creation
      of a sophisticated assay to measure blood levels of the drugs.
see above
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Maximum Concentration (Cmax) of Anti-VEGF Antibody
time frame: 1 month
description: The serum concentrations of anti-VEGF antibody (bevacizumab or ranibizumab) will be measured pre-injection as well as at various time points after injection (1 day, 1 week, 2 weeks, 1 month). These time points are selected based on previously completed animal studies. The Cmax will be compared between bevacizumab and ranibizumab.
arm group label: Ranibizumab
arm group type: Active Comparator
description: intravitreal injection of 0.5mg ranibizumab in usual fashion
arm group label: Bevacizumab
arm group type: Active Comparator
description: intravitreal injection of 1.25mg bevacizumab in usual fashion
intervention type: Drug
intervention name: Bevacizumab
description: Bevacizumab is an off-label but cheaper treatment for diabetic macular edema.
arm group label: Bevacizumab
other name: Avastin
intervention type: Drug
intervention name: Ranibizumab
description: Ranibizumab is a vascular endothelial growth factor inhibitor designed for ocular use
arm group label: Ranibizumab
other name: Lucentis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sanjay Sharma, MD MBA MSc FRCSC
role: Principal Investigator
affiliation: Department of Ophthalmology, Queen's University
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Queen's University
investigator full name: Dr. Sanjay Sharma
investigator title: Principal Investigator
mesh term: Macular Edema
mesh term: Edema
mesh term: Bevacizumab
mesh term: Ranibizumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 