<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/NCT02260544</url>
  </required_header>
  <id_info>
    <org_study_id>591-13</org_study_id>
    <nct_id>NCT02260544</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection</brief_title>
  <official_title>A Multicenter, Open Label, Balanced, Randomized, Two-treatment, Two-period, Two-sequence, Single Dose, Cross-over Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection 20mg/10mL of Dr. Reddy's Laboratories Ltd, India, With That of Doxorubicin Hydrochloride Liposome Injection 20 mg/10mL , Manufactured by: Sun Pharmaceutical Ind. Ltd, India; in Ovarian Cancer Patients Whose Disease Has Progressed or Recurred After Platinum Based Chemotherapy and Who Are Already Receiving or Scheduled to Start Therapy With the Reference Listed Drug Under Fasting Condition.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Reddy's Laboratories Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dr. Reddy's Laboratories Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bioequivalence study is proposed to be carried out on patients of ovarian cancer, who are&#xD;
      already receiving or who in the opinion of their treating physicians are candidates for&#xD;
      Doxorubicin liposomal injection therapy .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study has sequential two stage design. Bioequivalence based on encapsulated doxorubicin&#xD;
      will be tested at the end of stage 1. Power analysis will be performed for the primary&#xD;
      pharmacokinetic parameters of free Doxorubicin and liposome encapsulated Doxorubicin, for all&#xD;
      completed patients before bioequivalence evaluation. If observed power will be &gt;= 80% then&#xD;
      two one-sided 90% CI will be calculated for bioequivalence assessment at stage I.&#xD;
&#xD;
      If observed power will be &lt; 80% then bioequivalence will be evaluated at stage I. If&#xD;
      bioequivalence met then study will be stopped and if bioequivalence not met, then required&#xD;
      additional patients will be enrolled in stage II.&#xD;
&#xD;
      Each patient will be randomized to one of the two treatment sequences ( RT or TR ) according&#xD;
      to a randomization scheme prepared prior to the start of the trial. Serial blood samples for&#xD;
      determination of free doxorubicin and liposomal encapsulated doxorubicin plasma concentration&#xD;
      for PK analysis will be obtained in each cycle .&#xD;
&#xD;
      Bioequivalence Criteria : The 94.12% confidence intervals for the ratio of geometric least&#xD;
      squares means of ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf should&#xD;
      be within 80.00 to125.00% to conclude the test product is bioequivalent to the reference&#xD;
      product.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic ( PK ) parameter : the maximum plasma doxorubicin concentration ( Cmax ) [ Time frame : 2 cycles ]</measure>
    <time_frame>58 days</time_frame>
    <description>The study end point will use PK parameter ( Cmax ) for free doxorubicin and liposome encapsulated doxorubicin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameter : the areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation ( AUC 0-t)</measure>
    <time_frame>58 days</time_frame>
    <description>The study endpoint will use the PK parameter ( AUC 0-t) for free doxorubicin and liposome encapsulated doxorubicin ( AUC 0-t)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameter : the areas under the plasma concentration versus time curve extrapolated from 0 to infinity ( AUC 0-inf)</measure>
    <time_frame>58 days</time_frame>
    <description>The study endpoint will use the PK parameter ( AUC 0-Inf) for free doxorubicin and liposome encapsulated doxorubicin</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events ( TEAEs)</measure>
    <time_frame>58 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Ovarian Epithelial Cancer Recurrent</condition>
  <arm_group>
    <arm_group_label>Test Product - T</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>doxorubicin hydrochloride liposome ( Dr. Reddy's Lab )&#xD;
Use the test drug (doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Dr.Reddy's Laboratories Ltd., India) ; then use the reference drug ( doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Sun Pharma ) after at least 4-weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference Product - R</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>doxorubicin hydrochloride liposome ( Sun Pharma )&#xD;
Use the reference drug (doxorubicin Hydrochloride Liposome Injection 20mg/10mL i.e. 2mg/mL; from Sun Pharma ) ; then use the test drug ( doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Dr.Reddy's Laboratories Ltd., India) after at least 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin Hydrochloride Liposome Injection</intervention_name>
    <description>50mg/m2, IV on Day 1 of each cycle, On Day 1 of Cycle 2 , patients will crossover to the alternate reference or test formulation , After completion of Cycle 2 ( Day 28) , patients will be continued on the treatment of Doxorubicin Hydrochloride Liposome injection upto 4 more cycles if tolerance permits under guidance of their attending physicians.</description>
    <arm_group_label>Reference Product - R</arm_group_label>
    <arm_group_label>Test Product - T</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female of Indian Nationality , between 18-60n years of age&#xD;
&#xD;
          -  Able to understand investigational nature of this study and give written informed&#xD;
             consent prior to the participation in the trial.&#xD;
&#xD;
          -  Patients with ovarian cancer requiring Doxorubicin and whose disease has progressed or&#xD;
             recurred after platinum-based chemotherapy and who are already receiving or scheduled&#xD;
             to start therapy with reference listed drug&#xD;
&#xD;
          -  ECOG performance status ≤ 2&#xD;
&#xD;
          -  Cardiac function ( LVEF) ≥ 50%&#xD;
&#xD;
          -  patient with life expectancy of at least 3 months&#xD;
&#xD;
          -  Adequate hematopoietic, renal and liver function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior doxorubicin exposure that would result in a total lifetime exposure of 550mg/m2&#xD;
             or more after four cycles of treatment .&#xD;
&#xD;
          -  Pregnant or breast-feeding female&#xD;
&#xD;
          -  active opportunistic infection with mycobacteria , cytomegalovirus , toxoplasma&#xD;
&#xD;
          -  Impaired cardiac function including any of the following conditions within past 6&#xD;
             months :&#xD;
&#xD;
               1. Unstable angina&#xD;
&#xD;
               2. QTc prolongation or other significant ECG abnormalities&#xD;
&#xD;
               3. Coronary artery bypass graft surgery&#xD;
&#xD;
          -  History of hypersensitivity reactions attributed to a conventional formulation of&#xD;
             doxorubicin HCl or the components of Doxorubicin Hydrochloride liposome injection.&#xD;
&#xD;
          -  known brain metastasis&#xD;
&#xD;
          -  HIV positive antibody or syphilis&#xD;
&#xD;
          -  Patients with significantly impaired hepatic function&#xD;
&#xD;
          -  Clinically significant liver and kidney disease&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ashis Patnaik, MBBS, MD</last_name>
    <role>Study Director</role>
    <affiliation>Dr. Reddy's Laboratories Limited</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City Cancer Center</name>
      <address>
        <city>Vijaywada</city>
        <state>Andhra Pradesh</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nirmal Hospital Pvt Ltd</name>
      <address>
        <city>Surat</city>
        <state>Gujarat</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Srinivasam Cancer Care Hospitals India Private Limited</name>
      <address>
        <city>Bangalore</city>
        <state>Karnataka</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erode Cancer Center</name>
      <address>
        <city>Erode</city>
        <state>Karnataka</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Clinic and Nursing Home &amp; Jasleen Hospital</name>
      <address>
        <city>Nagpur</city>
        <state>Maharahtra</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Curie Manavta Cancer Centre</name>
      <address>
        <city>Nashik</city>
        <state>Maharashtra</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acharya HariHar Regional Cancer Centre</name>
      <address>
        <city>Cuttack</city>
        <state>Orissa</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meenakshi Mission Hospital &amp; Research Centre</name>
      <address>
        <city>Madurai</city>
        <state>Tamil Nadu</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr. G. Viswanathan Speciality Hospitals</name>
      <address>
        <city>Trichy</city>
        <state>Tamil Nadu</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bibi General Hospital</name>
      <address>
        <city>Hyderabad</city>
        <state>Telangana</state>
        <zip>500034</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MNJ Institute of Oncology &amp; Regional Cancer Centre</name>
      <address>
        <city>Hyderabad</city>
        <state>Telangana</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <link>
    <url>http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=9255&amp;EncHid=&amp;userName=</url>
    <description>CTRI web site India</description>
  </link>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>September 22, 2016</last_update_submitted>
  <last_update_submitted_qc>September 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 23, 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>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</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/NCT02260544
org study id: 591-13
nct id: NCT02260544
lead sponsor: 
has dmc: No
Bioequivalence study is proposed to be carried out on patients of ovarian cancer, who are
      already receiving or who in the opinion of their treating physicians are candidates for
      Doxorubicin liposomal injection therapy .
This study has sequential two stage design. Bioequivalence based on encapsulated doxorubicin
      will be tested at the end of stage 1. Power analysis will be performed for the primary
      pharmacokinetic parameters of free Doxorubicin and liposome encapsulated Doxorubicin, for all
      completed patients before bioequivalence evaluation. If observed power will be >= 80% then
      two one-sided 90% CI will be calculated for bioequivalence assessment at stage I.

      If observed power will be < 80% then bioequivalence will be evaluated at stage I. If
      bioequivalence met then study will be stopped and if bioequivalence not met, then required
      additional patients will be enrolled in stage II.

      Each patient will be randomized to one of the two treatment sequences ( RT or TR ) according
      to a randomization scheme prepared prior to the start of the trial. Serial blood samples for
      determination of free doxorubicin and liposomal encapsulated doxorubicin plasma concentration
      for PK analysis will be obtained in each cycle .

      Bioequivalence Criteria : The 94.12% confidence intervals for the ratio of geometric least
      squares means of ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf should
      be within 80.00 to125.00% to conclude the test product is bioequivalent to the reference
      product.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetic ( PK ) parameter : the maximum plasma doxorubicin concentration ( Cmax ) [ Time frame : 2 cycles ]
time frame: 58 days
description: The study end point will use PK parameter ( Cmax ) for free doxorubicin and liposome encapsulated doxorubicin
measure: PK parameter : the areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation ( AUC 0-t)
time frame: 58 days
description: The study endpoint will use the PK parameter ( AUC 0-t) for free doxorubicin and liposome encapsulated doxorubicin ( AUC 0-t)
measure: PK parameter : the areas under the plasma concentration versus time curve extrapolated from 0 to infinity ( AUC 0-inf)
time frame: 58 days
description: The study endpoint will use the PK parameter ( AUC 0-Inf) for free doxorubicin and liposome encapsulated doxorubicin
measure: Incidence of treatment-emergent adverse events ( TEAEs)
time frame: 58 days
arm group label: Test Product - T
arm group type: Experimental
description: doxorubicin hydrochloride liposome ( Dr. Reddy's Lab )
Use the test drug (doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Dr.Reddy's Laboratories Ltd., India) ; then use the reference drug ( doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Sun Pharma ) after at least 4-weeks.
arm group label: Reference Product - R
arm group type: Active Comparator
description: doxorubicin hydrochloride liposome ( Sun Pharma )
Use the reference drug (doxorubicin Hydrochloride Liposome Injection 20mg/10mL i.e. 2mg/mL; from Sun Pharma ) ; then use the test drug ( doxorubicin hydrochloride liposome Injection 20mg/10mL i.e. 2mg/mL from Dr.Reddy's Laboratories Ltd., India) after at least 4 weeks.
intervention type: Drug
intervention name: Doxorubicin Hydrochloride Liposome Injection
description: 50mg/m2, IV on Day 1 of each cycle, On Day 1 of Cycle 2 , patients will crossover to the alternate reference or test formulation , After completion of Cycle 2 ( Day 28) , patients will be continued on the treatment of Doxorubicin Hydrochloride Liposome injection upto 4 more cycles if tolerance permits under guidance of their attending physicians.
arm group label: Reference Product - R
arm group label: Test Product - T
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Ashis Patnaik, MBBS, MD
role: Study Director
affiliation: Dr. Reddy's Laboratories Limited
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: India
url: http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=9255&EncHid=&userName=
description: CTRI web site India
responsible party type: Sponsor
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin