<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/NCT04420871</url>
  </required_header>
  <id_info>
    <org_study_id>QL-KPTB-150</org_study_id>
    <nct_id>NCT04420871</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic and Safety Comparison of Two Capecitabine Tablets in Patients With Colorectal or Breast Cancer</brief_title>
  <official_title>Pharmacokinetic and Safety Comparison of Two Capecitabine Tablets in Patients With Colorectal or Breast Cancer Under Fed Conditions: a Multicenter, Randomized, Open-label, Three-period, and Reference-replicated Crossover Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Affiliated Hospital of Qingdao University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Affiliated Hospital of Qingdao University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A multicenter, randomized, open-label, three-period, and reference-replicated crossover study&#xD;
      was conducted in 48 patients with colorectal or breast cancer under fed conditions to assess&#xD;
      the bioequivalence between two formulations of capecitabine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a multicenter, open, random, balanced, three-period, three-sequence and&#xD;
      semi-repetitive cross study with 48 subjects. Eligible subjects were randomly assigned in a&#xD;
      1:1:1 ratio to receive one period of test formulation or two period of reference formulation,&#xD;
      followed by a 1-day washout period and administration of the alternate formulation. Serial&#xD;
      blood samples for pharmacokinetic assessment were collected at 0 hours (predose) up to 8&#xD;
      hours postdose. The plasma concentrations of capecitabine were analyzed by LC/MS-MS.&#xD;
      Pharmacokinetic parameters (non-compartmental model) were assessed with WinNonlin software.&#xD;
      The pharmacokinetic parameters assessed were area under the plasma concentration-time curve&#xD;
      from time 0 to the time of last measurable concentration (AUC0-t), AUC from time zero to&#xD;
      infinity (AUC0-∞), the peak plasma concentration of the drug (C max ), time needed to reach&#xD;
      maximum concentration (Tmax), the elimination half-life (t1/2), and terminal elimination rate&#xD;
      (λz). All were analyzed using an ANOVA model after logarithmic transformation of the data.&#xD;
      For establishing bioequivalence (BE) for capecitabine， reference-scaled average&#xD;
      bioequivalence (RSABE) acceptance criteria and average bioequivalence (ABE) acceptance&#xD;
      criteria were used. Safety and tolerability was assessed during the entire study period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 10, 2018</start_date>
  <completion_date type="Actual">January 26, 2019</completion_date>
  <primary_completion_date type="Actual">December 28, 2018</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>
    <intervention_model_description>A multicenter, randomized, open-label, three-period, and reference-replicated crossover study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peak Plasma Concentration (Cmax)</measure>
    <time_frame>18 days</time_frame>
    <description>Evaluation of Peak Plasma Concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)0-t</measure>
    <time_frame>18 days</time_frame>
    <description>Evaluation of Area under the plasma concentration versus time curve (AUC)0-t</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)0-∞</measure>
    <time_frame>18 days</time_frame>
    <description>Evaluation of Area under the plasma concentration versus time curve (AUC)0-∞</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>18 days</time_frame>
    <description>Adverse events were recorded to evaluate the safety of the studied drugs.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Patient Participation</condition>
  <arm_group>
    <arm_group_label>capecitabine reference formulation at a single dose of 150 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>capecitabine test formulation at a single dose of 150 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>150 mg of Xeloda®</intervention_name>
    <description>Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period. 150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.The subjects randomly received single oral administration of 150 mg of Xeloda®.</description>
    <arm_group_label>capecitabine reference formulation at a single dose of 150 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>150 mg of capecitabine</intervention_name>
    <description>Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period.The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.The subjects randomly received single oral administration of 150 mg of capecitabine.</description>
    <arm_group_label>capecitabine test formulation at a single dose of 150 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically or cytologically conﬁrmed colorectal or breast cancer&#xD;
             receiving capecitabine monotherapy or combination chemotherapy.&#xD;
&#xD;
          -  Eligible patients were within 18-70 years of age.&#xD;
&#xD;
          -  ECOG score was 0-2.&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) &gt; 50%.&#xD;
&#xD;
          -  There was no serious persistent toxicity to capecitabine treatment before screening&#xD;
             (laboratory tests ≤ grade 1 (NCI CTCAE 5.0 standard)&#xD;
&#xD;
          -  Hand-foot syndrome ≤ grade 2 after recovery from the previous treatment period).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients were known allergy to fluorouracil or 5-fluorouracil.&#xD;
&#xD;
          -  Patients with complete lack of known dihydropyrimidine dehydrogenase (DPD) activity.&#xD;
&#xD;
          -  Patients with abnormal hepatic and renal function (serum creatinine≤ 1.5 ×ULN; CLcr ≥&#xD;
             51 mL/min; bilirubin≤ 1.5 ×ULN; AST, ALT≤2.5×ULN)&#xD;
&#xD;
          -  Needed to accept phenytoin, warfarin, other coumarin derivatives anticoagulants, folic&#xD;
             acid, and CYP2C9 substrates during the research.&#xD;
&#xD;
          -  Patients with brain metastases or other metastases of the central nervous system&#xD;
             (except those who were treated at least 6 months prior to the start of the study and&#xD;
             were stable and asymptomatic).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>yu Cao, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>the study director of phase I clinical research center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Phase Ⅰ Clinical Research Center</name>
      <address>
        <city>Qingdao</city>
        <state>Shandong</state>
        <zip>266003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Capecitabine</keyword>
  <keyword>Bioequivalence</keyword>
  <keyword>Pharmacokinetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>All the technical achievements and outcomes of this trial are owned by Qilu Pharmaceutical Co., Ltd. and the research center. The research center can not publish any academic papers without the consent of the sponsor.</ipd_description>
  </patient_data>
  <!-- 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/NCT04420871
org study id: QL-KPTB-150
nct id: NCT04420871
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A multicenter, randomized, open-label, three-period, and reference-replicated crossover study
      was conducted in 48 patients with colorectal or breast cancer under fed conditions to assess
      the bioequivalence between two formulations of capecitabine.
This was a multicenter, open, random, balanced, three-period, three-sequence and
      semi-repetitive cross study with 48 subjects. Eligible subjects were randomly assigned in a
      1:1:1 ratio to receive one period of test formulation or two period of reference formulation,
      followed by a 1-day washout period and administration of the alternate formulation. Serial
      blood samples for pharmacokinetic assessment were collected at 0 hours (predose) up to 8
      hours postdose. The plasma concentrations of capecitabine were analyzed by LC/MS-MS.
      Pharmacokinetic parameters (non-compartmental model) were assessed with WinNonlin software.
      The pharmacokinetic parameters assessed were area under the plasma concentration-time curve
      from time 0 to the time of last measurable concentration (AUC0-t), AUC from time zero to
      infinity (AUC0-∞), the peak plasma concentration of the drug (C max ), time needed to reach
      maximum concentration (Tmax), the elimination half-life (t1/2), and terminal elimination rate
      (λz). All were analyzed using an ANOVA model after logarithmic transformation of the data.
      For establishing bioequivalence (BE) for capecitabine， reference-scaled average
      bioequivalence (RSABE) acceptance criteria and average bioequivalence (ABE) acceptance
      criteria were used. Safety and tolerability was assessed during the entire study period.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: A multicenter, randomized, open-label, three-period, and reference-replicated crossover study
primary purpose: Treatment
masking: None (Open Label)
measure: Peak Plasma Concentration (Cmax)
time frame: 18 days
description: Evaluation of Peak Plasma Concentration (Cmax)
measure: Area under the plasma concentration versus time curve (AUC)0-t
time frame: 18 days
description: Evaluation of Area under the plasma concentration versus time curve (AUC)0-t
measure: Area under the plasma concentration versus time curve (AUC)0-∞
time frame: 18 days
description: Evaluation of Area under the plasma concentration versus time curve (AUC)0-∞
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 18 days
description: Adverse events were recorded to evaluate the safety of the studied drugs.
arm group label: capecitabine reference formulation at a single dose of 150 mg
arm group type: Active Comparator
description: 150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.
arm group label: capecitabine test formulation at a single dose of 150 mg
arm group type: Experimental
description: The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.
intervention type: Drug
intervention name: 150 mg of Xeloda®
description: Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period. 150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.The subjects randomly received single oral administration of 150 mg of Xeloda®.
arm group label: capecitabine reference formulation at a single dose of 150 mg
intervention type: Drug
intervention name: 150 mg of capecitabine
description: Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period.The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.The subjects randomly received single oral administration of 150 mg of capecitabine.
arm group label: capecitabine test formulation at a single dose of 150 mg
criteria: 
gender: All
minimum age: 28 Years
maximum age: 69 Years
healthy volunteers: No
last name: yu Cao, Doctor
role: Principal Investigator
affiliation: the study director of phase I clinical research center
facility: 
country: China
responsible party type: Sponsor
mesh term: Capecitabine
sharing ipd: No
ipd description: All the technical achievements and outcomes of this trial are owned by Qilu Pharmaceutical Co., Ltd. and the research center. The research center can not publish any academic papers without the consent of the sponsor.