<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/NCT02241200</url>
  </required_header>
  <id_info>
    <org_study_id>DA3880_ANE_I</org_study_id>
    <nct_id>NCT02241200</nct_id>
  </id_info>
  <brief_title>A Study in Healthy Volunteers to Compare the Profiles of DA-3880 and EU Sourced ARANESP® (Amgen)</brief_title>
  <official_title>A Randomized, 2 Part, 4-treatment, 2-way Cross-over Study in Healthy Volunteers to Compare the Pharmacokinetic and Pharmacodynamic Profiles of 1ug/kg of DA-3880 and EU Sourced ARANESP® (Amgen) After Single Intravenous or Subcutaneous Administration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dong-A ST Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dong-A ST Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of the study is to determine whether the test product and the reference&#xD;
      product are bioequivalent based on the pharmacokinetics after administration of ug/kg as a&#xD;
      single intravenous dose and as a single subcutaneous dose of each of the formulations. The&#xD;
      study is consisted of randomization, 2 parts, 4 treatments, 2 way cross over.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2014</start_date>
  <completion_date type="Actual">November 29, 2014</completion_date>
  <primary_completion_date type="Actual">November 29, 2014</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of DA-3880 and Aranesp via IV Administration</measure>
    <time_frame>6 weeks</time_frame>
    <description>AUC0-t, Cmax, Tmax, t½, AUC0-inf, %AUC of DA-3880 and EU sourced Aranesp® (Amgen) after administration of 1 μg/kg as a single iv dose will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of DA-3880 and Aranesp via SC Administration</measure>
    <time_frame>6 weeks</time_frame>
    <description>AUC0-t, Cmax, Tmax, t½, AUC0-inf, %AUC of DA-3880 and EU sourced Aranesp® (Amgen) after administration of 1 μg/kg as a single sc dose will be assessed</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Variables of DA-3880 and Aranesp</measure>
    <time_frame>6 weeks</time_frame>
    <description>AUEC0-t, Emax, Tmax of DA-3880 and EU sourced Aranesp® after administration of 1 μg/kg as a single iv dose and as a single sc dose will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability Parameters of DA-3880 and Aranesp</measure>
    <time_frame>6 weeks</time_frame>
    <description>Adverse events, vital signs, 12-lead ECG, clinical laboratory tests, physical examination, immunogenicity (anti-drug antibodies), local tolerability of DA-3880 and EU sourced Aranesp® after administration of 1 μg/kg as a single iv dose and as a single sc dose will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic and Pharmacodynamic Variables of IV and SC Administration</measure>
    <time_frame>6 weeks</time_frame>
    <description>AUC0-t, Cmax, Tmax, t½, AUC0-inf, %AUC, AUEC0-t, Emax, Tmax of DA-3880 (1 μg/kg) and EU sourced Aranesp® (1 μg/kg) after iv administration with those after sc administration will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability Parameters of SC and IV Administration</measure>
    <time_frame>6 weeks</time_frame>
    <description>Adverse events, vital signs, 12-lead ECG, clinical laboratory tests, physical examination, immunogenicity (anti-drug antibodies), local tolerability of DA-3880 (1 μg/kg) and EU sourced Aranesp® (1 μg/kg) after iv administration with those after sc administration will be compared and assessed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Symptomatic Anemia</condition>
  <arm_group>
    <arm_group_label>IV Administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The iv solutions containing DA-3880 and Aranesp will be indistinguishable in appearance.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SC Administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The sc solutions containing DA-3880 and Aranesp will be indistinguishable in appearance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DA3880</intervention_name>
    <arm_group_label>IV Administration</arm_group_label>
    <arm_group_label>SC Administration</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aranesp</intervention_name>
    <arm_group_label>IV Administration</arm_group_label>
    <arm_group_label>SC Administration</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Gender : male or female&#xD;
&#xD;
          2. Age : 18 - 65 years, inclusive&#xD;
&#xD;
          3. Body Mass Index (BMI) : 18.0 - 30.0 kg/m2, inclusive&#xD;
&#xD;
          4. Weight : 55 - 105 kg, inclusive&#xD;
&#xD;
          5. Female subjects of childbearing potential must be non-pregnant and non-lactating, and&#xD;
             have a negative pregnancy test at screening and (each) admission to the clinical&#xD;
             research center&#xD;
&#xD;
          6. Females of child-bearing potential, with a fertile male sexual partner, should be&#xD;
             willing to use adequate contraception from screening until 90 days after the follow-up&#xD;
             visit. Adequate contraception is defined as using hormonal contraceptives or an&#xD;
             intrauterine device combined with at least 1 of the following forms of contraception:&#xD;
             a diaphragm or cervical cap, or a condom.&#xD;
&#xD;
          7. Males should be willing to use adequate contraception and not donate sperm from first&#xD;
             admission to the clinical research center until 90 days after the follow-up visit.&#xD;
             Adequate contraception for the male subject and his female partner, is defined as&#xD;
             using hormonal contraceptives or an intrauterine device combined with at least 1 of&#xD;
             the following forms of contraception: a diaphragm or cervical cap, or a condom.&#xD;
&#xD;
          8. All non-regular medication (including over the counter medication, health supplements,&#xD;
             and herbal remedies such as St. John's Wort extract) must have been stopped at least&#xD;
             14 days prior to (the first) admission to the clinical research center. An exception&#xD;
             is made for paracetamol (acetaminophen), which is allowed up to admission to the&#xD;
             clinical research center. Other exceptions are multivitamins and vitamin C, which are&#xD;
             allowed up to 7 days before admission to the clinical research center.&#xD;
&#xD;
          9. All regular non-topical medication must have been stopped at least 30 days prior to&#xD;
             (the first) admission the clinical research center. An exception is made for hormonal&#xD;
             contraceptives, which may be used throughout the study.&#xD;
&#xD;
         10. Ability and willingness to abstain from alcohol, methylxanthine-containing beverages&#xD;
             or food (coffee, tea, cola, chocolate, &quot;powerdrinks&quot;), grapefruit (juice) and tobacco&#xD;
             products from 48 h prior to each admission to in the clinical research center&#xD;
&#xD;
         11. Medical history without major pathology as judged by the PI&#xD;
&#xD;
         12. Normal resting supine blood pressure and pulse showing no clinically relevant&#xD;
             deviations as judged by the PI.&#xD;
&#xD;
         13. Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically&#xD;
             relevant pathology or showing no clinically relevant deviations as judged by the PI.&#xD;
&#xD;
         14. All values for clinical laboratory tests of blood and urine within the normal range or&#xD;
             showing no clinically relevant deviations as judged by the PI. Hb, Hct, RBC count and&#xD;
             thrombocytes should not exceed the upper limit of normal. Minor deviations can be&#xD;
             accepted at the discretion of the PI&#xD;
&#xD;
         15. Willing and able to sign the ICF&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of clinically relevant pathology&#xD;
&#xD;
          2. Mental handicap&#xD;
&#xD;
          3. History of relevant drug and/or food allergies, and/or latex allergy&#xD;
&#xD;
          4. Smoking more than 10 cigarettes, 2 cigars or 2 pipes daily; the use of tobacco&#xD;
             products in the 48 hours (2 days) prior to each admission to the clinical research&#xD;
             center is not allowed.&#xD;
&#xD;
          5. History of alcohol or drug abuse or drug addiction (including soft drugs like cannabis&#xD;
             products)&#xD;
&#xD;
          6. Positive drug screen (opiates, methadone, cocaine, amphetamines [including ecstasy],&#xD;
             cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol)&#xD;
&#xD;
          7. Average intake of more than 24 units of alcohol per week: one unit of alcohol equals&#xD;
             approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)&#xD;
&#xD;
          8. Consumption of any foods containing poppy seeds within 48 hours (2 days) prior to each&#xD;
             admission to the clinical research center as this could cause a false positive drug&#xD;
             screen result&#xD;
&#xD;
          9. Positive screen on hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV)&#xD;
             antibodies or anti-HIV 1 and 2 antibodies&#xD;
&#xD;
         10. Participation in a drug study within 60 days prior to the screening visit in the&#xD;
             current study. Participation in more than 3 other drug studies (for men) and more than&#xD;
             2 other drug studies (for women) in the 10 months prior to the first drug&#xD;
             administration in the current study&#xD;
&#xD;
         11. Donation or loss of more than 100 mL of blood within 60 days prior to the first drug&#xD;
             administration. Donation or loss of more than 1.5 liters of blood (for men) / more&#xD;
             than 1.0 liters of blood (for women) in the 10 months prior to the first drug&#xD;
             administration in the current study.&#xD;
&#xD;
         12. Strenuous exercise within 96 hours (4 days) prior to each admission to the clinical&#xD;
             research center.&#xD;
&#xD;
         13. Significant and/or acute illness within 5 days prior to the first drug administration&#xD;
             that may impact safety assessments, in the opinion of the PI&#xD;
&#xD;
         14. Vaccination within 30 days prior to entry into the clinical research center or&#xD;
             planning a vaccination before the follow-up visit&#xD;
&#xD;
         15. History of a significant respiratory disorder (such as asthma) or significant immune&#xD;
             disorder&#xD;
&#xD;
         16. Significant infection within 30 days prior to entry into the clinical research center&#xD;
&#xD;
         17. History of epilepsy; a single febrile convulsion at an age &lt; 6 years is acceptable&#xD;
&#xD;
         18. History of hemoglobinopathy or abnormal Hb in first-degree relatives&#xD;
&#xD;
         19. A previous administration of any erythropoiesis-stimulating agent including EPO or&#xD;
             darbepoetin, if known&#xD;
&#xD;
         20. Previous immunoglobulin or iron supplementation within 3 months prior to the screening&#xD;
             visit&#xD;
&#xD;
         21. History of hypersensitivity reactions for any EPO, darbepoetin, iron supplements, or&#xD;
             excipient of the investigational product&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>PRA</name>
      <address>
        <city>Zuidlaren</city>
        <zip>9471</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>June 13, 2021</last_update_submitted>
  <last_update_submitted_qc>June 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Darbepoetin alfa</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/NCT02241200
org study id: DA3880_ANE_I
nct id: NCT02241200
lead sponsor: 
has dmc: No
The main purpose of the study is to determine whether the test product and the reference
      product are bioequivalent based on the pharmacokinetics after administration of ug/kg as a
      single intravenous dose and as a single subcutaneous dose of each of the formulations. The
      study is consisted of randomization, 2 parts, 4 treatments, 2 way cross over.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pharmacokinetics of DA-3880 and Aranesp via IV Administration
time frame: 6 weeks
description: AUC0-t, Cmax, Tmax, t½, AUC0-inf, %AUC of DA-3880 and EU sourced Aranesp® (Amgen) after administration of 1 μg/kg as a single iv dose will be assessed.
measure: Pharmacokinetics of DA-3880 and Aranesp via SC Administration
time frame: 6 weeks
description: AUC0-t, Cmax, Tmax, t½, AUC0-inf, %AUC of DA-3880 and EU sourced Aranesp® (Amgen) after administration of 1 μg/kg as a single sc dose will be assessed
measure: Pharmacodynamic Variables of DA-3880 and Aranesp
time frame: 6 weeks
description: AUEC0-t, Emax, Tmax of DA-3880 and EU sourced Aranesp® after administration of 1 μg/kg as a single iv dose and as a single sc dose will be assessed.
measure: Safety and Tolerability Parameters of DA-3880 and Aranesp
time frame: 6 weeks
description: Adverse events, vital signs, 12-lead ECG, clinical laboratory tests, physical examination, immunogenicity (anti-drug antibodies), local tolerability of DA-3880 and EU sourced Aranesp® after administration of 1 μg/kg as a single iv dose and as a single sc dose will be assessed.
measure: Pharmacodynamic and Pharmacodynamic Variables of IV and SC Administration
time frame: 6 weeks
description: AUC0-t, Cmax, Tmax, t½, AUC0-inf, %AUC, AUEC0-t, Emax, Tmax of DA-3880 (1 μg/kg) and EU sourced Aranesp® (1 μg/kg) after iv administration with those after sc administration will be assessed.
measure: Safety and Tolerability Parameters of SC and IV Administration
time frame: 6 weeks
description: Adverse events, vital signs, 12-lead ECG, clinical laboratory tests, physical examination, immunogenicity (anti-drug antibodies), local tolerability of DA-3880 (1 μg/kg) and EU sourced Aranesp® (1 μg/kg) after iv administration with those after sc administration will be compared and assessed.
arm group label: IV Administration
arm group type: Experimental
description: The iv solutions containing DA-3880 and Aranesp will be indistinguishable in appearance.
arm group label: SC Administration
arm group type: Experimental
description: The sc solutions containing DA-3880 and Aranesp will be indistinguishable in appearance.
intervention type: Drug
intervention name: DA3880
arm group label: IV Administration
arm group label: SC Administration
intervention type: Drug
intervention name: Aranesp
arm group label: IV Administration
arm group label: SC Administration
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Darbepoetin alfa