<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/NCT02237690</url>
  </required_header>
  <id_info>
    <org_study_id>Libaoduo-BE-002</org_study_id>
    <nct_id>NCT02237690</nct_id>
  </id_info>
  <brief_title>Assess Bioequivalence of Two Formulations of Doxorubicin Hydrochloride Liposome in Female Patients With Ovarian Cancer</brief_title>
  <official_title>A Randomized, Open Label, Single-Dose, Two-Cycle Crossover Study to Assess Bioequivalence of Test and Reference Formulations of Doxorubicin Hydrochloride Liposome Injection in Female Patients With Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, single-dose, open-label, randomized, balanced, two-treatment,&#xD;
      two-cycle, two-sequence crossover study to assess bioequivalence of test (T) and reference&#xD;
      (R) formulations of doxorubicin hydrochloride liposome injection in female patients with&#xD;
      ovarian cancer.&#xD;
&#xD;
      Each patient will be randomized to one of two treatment sequences (RT or TR) according to a&#xD;
      randomization scheme prepared prior to the start of the trial.There will be at least 4-week&#xD;
      apart between each single-dose administration. Serial blood samples for determination of free&#xD;
      doxorubicin and liposomal encapsulated doxorubicin plasma concentrations for PK analysis will&#xD;
      be obtained in each cycle.&#xD;
&#xD;
      The 90% confidence intervals on the GMR(geometric mean ratio) of test to reference products&#xD;
      of free and liposome encapsulated doxorubicin for PK must be within 80-125% to demonstrate&#xD;
      bioequivalence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study has an adaptive 2-stage design. Bioequivalence based on encapsulated doxorubicin&#xD;
      will be tested at the end of Stage 1 . An interim analysis of free doxorubicin will be&#xD;
      performed at the end of Stage 1 . If needed, the study may continue into Stage 2 with&#xD;
      additional number of ovarian cancer patients determined based on the interim analysis; and a&#xD;
      final evaluation of bioequivalence for free doxorubicin will be performed at the end of Stage&#xD;
      2. Each patient will be randomized to one of two treatment sequences (RT or TR) according to&#xD;
      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&#xD;
      concentrations for PK analysis will be obtained in each cycle.&#xD;
&#xD;
      The 90% confidence intervals on the GMR（geometric mean ratio） of test to reference products&#xD;
      of free and liposome encapsulated doxorubicin for PK must be within 80-125% to demonstrate&#xD;
      bioequivalence.&#xD;
&#xD;
      Safety data will be summarized and listed. Adverse events will be coded and classified by&#xD;
      system organ class and preferred term using Common Terminology Criteria for Adverse Events. A&#xD;
      summary of all drug-related adverse events will also be generated. Clinical laboratory data&#xD;
      will be summarized descriptively and listed by treatment group. The change from pre dose to&#xD;
      the end of the study will also be summarized. Prior and concomitant medications will be coded&#xD;
      with the World Health Organization Drug Dictionary and listed. Vital signs and&#xD;
      electrocardiogram data will be summarized and listed by dose group and visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">August 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 concentrations(Cmax)</measure>
    <time_frame>2 cycles</time_frame>
    <description>The study endpoint will use the 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(AUC0-t)</measure>
    <time_frame>2 cycles</time_frame>
    <description>The study endpoint will use the PK parameter(AUC0-t) for free doxorubicin and liposome encapsulated doxorubicin(AUC0-t)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameter:the areas under the plasma concentration versus time curve extrapolated from 0 to infinity(AUC0-inf)</measure>
    <time_frame>2 cycles</time_frame>
    <description>The study endpoint will use the PK parameter(AUC0-inf) for free doxorubicin and liposome encapsulated doxorubicin</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>incidence of treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>2 cycles</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>study discontinuation information</measure>
    <time_frame>2 cycles</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>doxorubicin hydrochloride liposome（Libaoduo）</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Use the test drug(doxorubicin hydrochloride liposome-Libaoduo,from Fudan-Zhangjiang ),then use the reference drug(doxorubicin hydrochloride liposome，from Sunpharma) after at least 4-weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>doxorubicin hydrochloride liposome</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Use the reference drug(doxorubicin hydrochloride liposome，from Sunpharma),then use the test drug drug(doxorubicin hydrochloride liposome-Libaoduo,from Fudan-Zhangjiang) after at least 4-weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin hydrochloride liposome</intervention_name>
    <description>50mg/m2,IV on day1 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 up to 4 more cycles if tolerance permits under guidance of their attending physicians.</description>
    <arm_group_label>doxorubicin hydrochloride liposome</arm_group_label>
    <arm_group_label>doxorubicin hydrochloride liposome（Libaoduo）</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to give written informed consent for participation in the trial;&#xD;
&#xD;
          -  Females age 18 to 75 years, inclusive;&#xD;
&#xD;
          -  Histologically or cytologically proven ovarian cancer, which has progressed or&#xD;
             recurred by CT/MRI confirmation after platinum-based chemotherapy;&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) Performance Status 0 - 2;&#xD;
&#xD;
          -  Patient is expected to be able to receive both doses of Doxorubicin Hydrochloride&#xD;
             Liposome Injection and participate in the trial for at least 56 days.&#xD;
&#xD;
          -  Urine pregnancy test before dosing of both cycle1 and cycle 2 must be negative (not&#xD;
             including postmenopausal or surgically sterile women); Agree to use an approved method&#xD;
             of birth control (condom with spermicide, diaphragm or cervical cap with spermicide,&#xD;
             or intrauterine device); or patients of non-childbearing potential who are either&#xD;
             surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation)&#xD;
             or &gt;1 year postmenopausal with follicle-stimulating hormone in the postmenopausal&#xD;
             range;&#xD;
&#xD;
               -  30days or 5 half-lives (whichever is longer) have elapsed from the completion of&#xD;
                  previous cancer therapy, and patients must have recovered to &lt; Grade 2 or be at&#xD;
                  new stable baseline from any related toxicities;&#xD;
&#xD;
          -  Adequate renal, hepatic and bone marrow function without blood product or&#xD;
             hematopoietic growth factor support:&#xD;
&#xD;
          -  Able to comply with study requirements in the opinion of the Principal Investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant allergy, hypersensitivity or idiosyncratic reactions to doxorubicin and/or&#xD;
             any related compounds;&#xD;
&#xD;
          -  History or presence of cardiac disease rated New York State Heart Association&#xD;
             Classification class 2 or greater;&#xD;
&#xD;
          -  Uncontrolled cardiac arrhythmia or other findings on screening electrocardiogram (ECG)&#xD;
             which could, in the judgment of the Principal Investigator, put the patient at undue&#xD;
             risk for participation in the trial;&#xD;
&#xD;
          -  LVEF（left ventricular ejection fraction） below 50% or below institutional normal at&#xD;
             screening;&#xD;
&#xD;
          -  Prior radiation therapy to mediastinum;&#xD;
&#xD;
          -  Concomitant use of other cytotoxic or cytostatic drugs or of radiotherapy;&#xD;
&#xD;
          -  Active, uncontrolled infection, including opportunistic infection with mycobacteria,&#xD;
             cytomegalovirus, toxoplasma, or P. carinii;&#xD;
&#xD;
          -  Use of prescription or non-prescription herbal and dietary supplements, within 7 days&#xD;
             or 5 half-lives (whichever is longer) prior to the first dose of study medication.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wu li ngying, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kong be ihua, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shandong University Qilu Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Liu ji hong, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Institute&amp; Hospital, Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>QiLu Hospital of Shandong University</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250012</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>August 31, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>June 1, 2017</last_update_submitted>
  <last_update_submitted_qc>June 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2017</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>Ovarian Neoplasms</mesh_term>
    <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/NCT02237690
org study id: Libaoduo-BE-002
nct id: NCT02237690
lead sponsor: 
has dmc: No
This is a multi-center, single-dose, open-label, randomized, balanced, two-treatment,
      two-cycle, two-sequence crossover study to assess bioequivalence of test (T) and reference
      (R) formulations of doxorubicin hydrochloride liposome injection in female patients with
      ovarian cancer.

      Each patient will be randomized to one of two treatment sequences (RT or TR) according to a
      randomization scheme prepared prior to the start of the trial.There will be at least 4-week
      apart between each single-dose administration. Serial blood samples for determination of free
      doxorubicin and liposomal encapsulated doxorubicin plasma concentrations for PK analysis will
      be obtained in each cycle.

      The 90% confidence intervals on the GMR(geometric mean ratio) of test to reference products
      of free and liposome encapsulated doxorubicin for PK must be within 80-125% to demonstrate
      bioequivalence.
This study has an adaptive 2-stage design. Bioequivalence based on encapsulated doxorubicin
      will be tested at the end of Stage 1 . An interim analysis of free doxorubicin will be
      performed at the end of Stage 1 . If needed, the study may continue into Stage 2 with
      additional number of ovarian cancer patients determined based on the interim analysis; and a
      final evaluation of bioequivalence for free doxorubicin will be performed at the end of Stage
      2. Each patient will be randomized to one of 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
      concentrations for PK analysis will be obtained in each cycle.

      The 90% confidence intervals on the GMR（geometric mean ratio） of test to reference products
      of free and liposome encapsulated doxorubicin for PK must be within 80-125% to demonstrate
      bioequivalence.

      Safety data will be summarized and listed. Adverse events will be coded and classified by
      system organ class and preferred term using Common Terminology Criteria for Adverse Events. A
      summary of all drug-related adverse events will also be generated. Clinical laboratory data
      will be summarized descriptively and listed by treatment group. The change from pre dose to
      the end of the study will also be summarized. Prior and concomitant medications will be coded
      with the World Health Organization Drug Dictionary and listed. Vital signs and
      electrocardiogram data will be summarized and listed by dose group and visit.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: pharmacokinetic（PK） parameter:the maximum plasma doxorubicin concentrations(Cmax)
time frame: 2 cycles
description: The study endpoint will use the 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(AUC0-t)
time frame: 2 cycles
description: The study endpoint will use the PK parameter(AUC0-t) for free doxorubicin and liposome encapsulated doxorubicin(AUC0-t)
measure: PK parameter:the areas under the plasma concentration versus time curve extrapolated from 0 to infinity(AUC0-inf)
time frame: 2 cycles
description: The study endpoint will use the PK parameter(AUC0-inf) for free doxorubicin and liposome encapsulated doxorubicin
measure: incidence of treatment-emergent adverse events (TEAEs)
time frame: 2 cycles
measure: study discontinuation information
time frame: 2 cycles
arm group label: doxorubicin hydrochloride liposome（Libaoduo）
arm group type: Experimental
description: Use the test drug(doxorubicin hydrochloride liposome-Libaoduo,from Fudan-Zhangjiang ),then use the reference drug(doxorubicin hydrochloride liposome，from Sunpharma) after at least 4-weeks.
arm group label: doxorubicin hydrochloride liposome
arm group type: Active Comparator
description: Use the reference drug(doxorubicin hydrochloride liposome，from Sunpharma),then use the test drug drug(doxorubicin hydrochloride liposome-Libaoduo,from Fudan-Zhangjiang) after at least 4-weeks.
intervention type: Drug
intervention name: Doxorubicin hydrochloride liposome
description: 50mg/m2,IV on day1 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 up to 4 more cycles if tolerance permits under guidance of their attending physicians.
arm group label: doxorubicin hydrochloride liposome
arm group label: doxorubicin hydrochloride liposome（Libaoduo）
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Wu li ngying, Ph.D
role: Principal Investigator
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
last name: Kong be ihua, Ph.D
role: Principal Investigator
affiliation: Shandong University Qilu Hospital
last name: Liu ji hong, Ph.D
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin