<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/NCT01668121</url>
  </required_header>
  <id_info>
    <org_study_id>3103012</org_study_id>
    <nct_id>NCT01668121</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study on Budesonide/Formoterol Device-metered Dry Powder Inhalers</brief_title>
  <acronym>REFLI</acronym>
  <official_title>Pharmacokinetic Study on Budesonide/Formoterol Device-metered Dry Powder Inhalers, Two Batches of Symbicort Turbuhaler and Budesonide/Formoterol Easyhaler: Randomised, Double-blind, Double-dummy, Single Centre, Single Dose, Crossover Study in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Orion Corporation, Orion Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Orion Corporation, Orion Pharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the acceptance range with which two&#xD;
      Symbicort Turbohaler batches could be declared bioequivalent in a bioequivalence setting. The&#xD;
      secondary objective is to compare pharmacokinetic parameters of the reference product batches&#xD;
      and Budesonide/formoterol Easyhaler.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 2012</completion_date>
  <primary_completion_date type="Actual">November 2012</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic parameter Cmax of plasma Budesonide concentration</measure>
    <time_frame>within 12 h</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameter AUCt of plasma Budesonide concentration</measure>
    <time_frame>within 12 h</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameter Cmax of plasma Formoterol concentration</measure>
    <time_frame>within 24 h</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameter AUCt of plasma Formoterol concentration</measure>
    <time_frame>within 24 h</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Symbicort Turbohaler</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Symbicort Turbohaler</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Budesonide/formoterol Easyhaler</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Budesonide/formoterol Easyhaler</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Symbicort Turbohaler</intervention_name>
    <arm_group_label>Budesonide/formoterol Easyhaler</arm_group_label>
    <arm_group_label>Symbicort Turbohaler</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Budesonide/formoterol Easyhaler</intervention_name>
    <arm_group_label>Budesonide/formoterol Easyhaler</arm_group_label>
    <arm_group_label>Symbicort Turbohaler</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent (IC) obtained.&#xD;
&#xD;
          2. Males and females, 18-55 (inclusive) years of age.&#xD;
&#xD;
          3. Normal weight defined as body mass index (BMI) &gt; 19 and &lt; 30 kg/m2 (BMI=&#xD;
             weight/height2).&#xD;
&#xD;
          4. Weight at least 50 kg.&#xD;
&#xD;
          5. Forced expiratory volume in one second (FEV1) at least 80% of the predicted value&#xD;
             measured at the screening.&#xD;
&#xD;
          6. Good general health ascertained by detailed medical history, and laboratory and&#xD;
             physical examinations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Vulnerable subjects (i.e. persons under any administrative or legal supervision).&#xD;
&#xD;
          2. Evidence of a clinically significant cardiovascular, renal, hepatic, haematological,&#xD;
             gastrointestinal, pulmonary, metabolic-endocrine, neurological or psychiatric disease&#xD;
             within previous 2 years; or evidence of active or quiescent pulmonary tuberculosis,&#xD;
             fungal and viral infections in the airways.&#xD;
&#xD;
          3. Any condition requiring regular concomitant treatment (including vitamins and herbal&#xD;
             products) or likely to need any concomitant treatment during the study. As an&#xD;
             exception, paracetamol and ibuprofen for occasional pain are allowed.&#xD;
&#xD;
          4. Intake of any medication that could affect the outcome of the study. As an exception,&#xD;
             contraceptives and hormone replacement therapy are allowed. The use of medicines which&#xD;
             are strong CYP3A4 inducers or inhibitors are restricted for at least 2 weeks prior to&#xD;
             the first study treatment administration and during the study.&#xD;
&#xD;
          5. Any clinically significant abnormal laboratory value or physical finding (including&#xD;
             electrocardiogram [ECG] and vital signs) that may interfere with the interpretation of&#xD;
             test results or cause a health risk for the subject if he/she participates in the&#xD;
             study, as judged by the investigator. More specifically, supine HR &lt; 45 or &gt; 100 bpm&#xD;
             after 10-min rest or supine systolic BP &gt;140 or &lt; 90 or diastolic BP &gt; 90 or &lt; 60 mmHg&#xD;
             after a 10-minute rest, or a QTc-Bazett (QTcB interval) &gt; 450 msec at screening&#xD;
             evaluation.&#xD;
&#xD;
          6. Known hypersensitivity to the active substances or the excipient (lactose, which&#xD;
             contains small amounts of milk protein) of the drug.&#xD;
&#xD;
          7. History of vasovagal collapses.&#xD;
&#xD;
          8. History of anaphylactic/anaphylactoid reactions.&#xD;
&#xD;
          9. History of seizures including febrile seizures.&#xD;
&#xD;
         10. Pregnant or lactating females.&#xD;
&#xD;
         11. Females of childbearing potential if they are not using proper contraception&#xD;
             (mechanical and/or hormonal contraception, intrauterine device [IUD] or surgical&#xD;
             sterilization). Double method of contraception is needed when using oral or mechanical&#xD;
             contraception: e.g. condom in conjunct with oral contraception and spermicidal product&#xD;
             with mechanical contraception (please see section 5.7 for details).&#xD;
&#xD;
         12. Recent or current (suspected) drug abuse or positive result in the drugs abuse test.&#xD;
&#xD;
         13. Recent or current alcohol abuse (regular drinking more than 21 units per week for&#xD;
             males and more than 16 units per week for females [1 unit = 4 cl spirits or&#xD;
             equivalent]).&#xD;
&#xD;
         14. Current use of nicotine containing products more than 5 cigarettes (or equivalent)/day&#xD;
             and/or inability to refrain from the use of nicotine containing products during the&#xD;
             study (from the screening visit to the end-of-study visit).&#xD;
&#xD;
         15. Use of caffeine containing beverages more than 600 mg of caffeine/day and/or inability&#xD;
             to refrain from the use of caffeine containing beverages during the treatment periods&#xD;
             until 24 h after study treatment administration.&#xD;
&#xD;
         16. Blood donation or loss of significant amount of blood within 30 days prior to the&#xD;
             first study treatment administration.&#xD;
&#xD;
         17. Administration of another investigational drug within 30 days prior to the first study&#xD;
             treatment administration.&#xD;
&#xD;
         18. Unsuitable veins for repeated venepuncture or for cannulation.&#xD;
&#xD;
         19. Inability to learn the correct inhalation technique.&#xD;
&#xD;
         20. Predictable poor compliance or inability to communicate well with the study centre&#xD;
             personnel.&#xD;
&#xD;
         21. Inability to participate in all treatment periods.&#xD;
&#xD;
         22. The subject is not able to understand and comply with protocol requirements,&#xD;
             instructions and protocol-stated restrictions.&#xD;
&#xD;
         23. Positive result in HIV, hepatitis B or C tests.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rainard Fuhr, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parexel</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Merja Mäkitalo</last_name>
    <role>Study Director</role>
    <affiliation>Orion Corporation, Orion Pharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PAREXEL International GmbH</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>November 22, 2012</last_update_submitted>
  <last_update_submitted_qc>November 22, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 27, 2012</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>Budesonide</mesh_term>
    <mesh_term>Formoterol Fumarate</mesh_term>
    <mesh_term>Budesonide, Formoterol Fumarate Drug Combination</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/NCT01668121
org study id: 3103012
nct id: NCT01668121
lead sponsor: 
has dmc: No
The primary objective of this study is to evaluate the acceptance range with which two
      Symbicort Turbohaler batches could be declared bioequivalent in a bioequivalence setting. The
      secondary objective is to compare pharmacokinetic parameters of the reference product batches
      and Budesonide/formoterol Easyhaler.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Pharmacokinetic parameter Cmax of plasma Budesonide concentration
time frame: within 12 h
measure: Pharmacokinetic parameter AUCt of plasma Budesonide concentration
time frame: within 12 h
measure: Pharmacokinetic parameter Cmax of plasma Formoterol concentration
time frame: within 24 h
measure: Pharmacokinetic parameter AUCt of plasma Formoterol concentration
time frame: within 24 h
arm group label: Symbicort Turbohaler
arm group type: Experimental
description: Symbicort Turbohaler
arm group label: Budesonide/formoterol Easyhaler
arm group type: Active Comparator
description: Budesonide/formoterol Easyhaler
intervention type: Drug
intervention name: Symbicort Turbohaler
arm group label: Budesonide/formoterol Easyhaler
arm group label: Symbicort Turbohaler
intervention type: Drug
intervention name: Budesonide/formoterol Easyhaler
arm group label: Budesonide/formoterol Easyhaler
arm group label: Symbicort Turbohaler
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rainard Fuhr, MD
role: Principal Investigator
affiliation: Parexel
last name: Merja Mäkitalo
role: Study Director
affiliation: Orion Corporation, Orion Pharma
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Budesonide
mesh term: Formoterol Fumarate
mesh term: Budesonide, Formoterol Fumarate Drug Combination