<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/NCT04466176</url>
  </required_header>
  <id_info>
    <org_study_id>BECRO/RESP/BE250-PIVOTAL</org_study_id>
    <nct_id>NCT04466176</nct_id>
  </id_info>
  <brief_title>A Pivotal Bioequivalence Study Between Fluticasone Propionate 250 mcg and Salmeterol Xinafoate 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 250/50 Inhalation Powder/GSK in Healthy Volunteers</brief_title>
  <official_title>A Pivotal, Randomized, Single-dose, Open Label, Two-treatment, Two-sequence, Two-period, Crossover Study Under Fasting Conditions to Examine the Bioequivalence Between Fluticasone Propionate 250 mcg and Salmeterol Xinafoate 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 250/50 Inhalation Powder/GSK in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Respirent Pharmaceuticals Co Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Becro Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Respirent Pharmaceuticals Co Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bioequivalence study between two inhaler products of fixed dose combination of fluticasone&#xD;
      propionate and salmeterol xinafoate inhalation powder&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A bioequivalence study of a single dose of the fixed-dose combination of fluticasone&#xD;
      propionate and salmeterol xinafoate inhalation powder administered from Fluticasone&#xD;
      propionate 250 mcg and Salmeterol xinafoate 50 mcg inhalation powder/Respirent&#xD;
      Pharmaceuticals (test-Τ) as 2 inhalations and ADVAIR DISKUS® 250/50 mcg inhalation powder/GSK&#xD;
      (reference-R) in healthy volunteers under fasting conditions. The study will be one-center&#xD;
      crossover, randomized, 2-period, 2-sequence (RT and TR), single dose, laboratory-blinded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 4, 2020</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>One-center crossover, randomized, 2-period, 2-sequence (RT and TR), single dose, laboratory-blinded study</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>laboratory-blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>up to 36 hours post-administration</time_frame>
    <description>Maximum plasma concentration, it is read directly from the raw data</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t)</measure>
    <time_frame>up to 36 hours post-administration</time_frame>
    <description>Area under the plasma concentration curve from time 0 to the last measured</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞</measure>
    <time_frame>up to 36 hours post-administration</time_frame>
    <description>Area under the plasma concentration-time curve extrapolated to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>up to 36 hours post-administration</time_frame>
    <description>Time until Cmax is reached, it is read directly from the observed concentrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2</measure>
    <time_frame>up to 36 hours post-administration</time_frame>
    <description>Plasma concentration halflife, it is calculated from the ratio 0.693/λZ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz</measure>
    <time_frame>up to 36 hours post-administration</time_frame>
    <description>Terminal elimination rate constant, calculated from the slope of the final phase of the ln-concentration curve versus time with regression analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual area</measure>
    <time_frame>up to 36 hours post-administration</time_frame>
    <description>[AUC(0-∞)-AUC(0-t)]/AUC(0-∞)]</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>Test Product</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference Product</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ADVAIR DISKUS® 250/50</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Test Product</intervention_name>
    <description>2 inhalations of Test and Reference product in each study period</description>
    <arm_group_label>Test Product</arm_group_label>
    <other_name>Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Reference Product</intervention_name>
    <description>2 inhalations of Test and Reference product in each study period</description>
    <arm_group_label>Reference Product</arm_group_label>
    <other_name>ADVAIR DISKUS 250/50</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy volunteers of both genders, aged ≥18 and ≤60 years.&#xD;
&#xD;
          2. Subjects with Body Mass Index (ΒΜΙ) ≥18.5 and &lt;30.0 kg/m2.&#xD;
&#xD;
          3. Healthy volunteers are declared healthy based on medical history, physical&#xD;
             examination, ECG, pulmonary function test (a forced expiratory volume in 1 second&#xD;
             (FEV1) ≥80% of the predicted normal value), and clinical laboratory values within the&#xD;
             laboratory stated normal range; if not within this range, they must be without any&#xD;
             clinical significance according to the Investigator.&#xD;
&#xD;
          4. Females who participate in the study are either at reproductive age i.e.pre-menopausal&#xD;
             or unable to gestate [i.e. post-menopausal (absence of menses for 12 months prior to&#xD;
             drug administration), hysterectomy, bilateral oophorectomy, tubal ligation at least 6&#xD;
             months prior to drug administration].&#xD;
&#xD;
          5. Subjects that are non-smokers.&#xD;
&#xD;
          6. Subjects that, in the opinion of the principal investigator/medical officer, are able&#xD;
             to communicate and comply with the study procedures and protocol restrictions as&#xD;
             evidenced by the Informed Consent Form (ICF) duly read, signed and dated by the&#xD;
             subject prior to study initiation.&#xD;
&#xD;
          7. Subjects able to use the inhalers according to given instructions, as judged by the&#xD;
             Investigator or study nurse.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity to the active substance(s) or to the excipient (lactose which&#xD;
             contains small amounts of milk protein may cause allergic reactions) or related class&#xD;
             (any sympathomimetic drug or any inhaled, intranasal, or systemic corticosteroid&#xD;
             therapy) of the medicinal product&#xD;
&#xD;
          2. Clinically significant illness or surgery within four weeks prior to dosing.&#xD;
&#xD;
          3. Clinically significant ECG abnormalities or vital sign abnormalities (seated systolic&#xD;
             blood pressure &lt;90 or &gt;140 mmHg, seated diastolic blood pressure &lt;50 or &gt;90 mmHg or&#xD;
             heart rate less than 50 or over 100 bpm) at screening.&#xD;
&#xD;
          4. Clinically significant history or presence of chronic bronchitis, emphysema,asthma or&#xD;
             any other lung disease.&#xD;
&#xD;
          5. History or presence of pulmonary tuberculosis.&#xD;
&#xD;
          6. Viral or bacterial, upper or lower respiratory tract infection or sinus or middle ear&#xD;
             infection within 4 weeks prior to the screening visit.&#xD;
&#xD;
          7. History or presence of significant cardiovascular, endocrinal, neurologic,&#xD;
             immunological, psychiatric or metabolic disease.&#xD;
&#xD;
          8. History of significant alcohol or drug abuse within one year prior to the screening&#xD;
             visit.&#xD;
&#xD;
          9. Regular use of alcohol within six months prior to screening visit (more than 14&#xD;
             alcohol units per week) [1Unit =150 ml of wine, 360 ml of beer, or 45 ml of 40%&#xD;
             alcohol].&#xD;
&#xD;
         10. Inability to abstain from alcohol for the duration of study period.&#xD;
&#xD;
         11. Presence of disease markers for Hepatitis B, Hepatitis C or HIV at screening.&#xD;
&#xD;
         12. Positive results for drugs of abuse (barbiturates, marijuana, opioids, benzodiazepines&#xD;
             and methadone) in saliva before each administration.&#xD;
&#xD;
         13. Positive alcohol breath test before each administration.&#xD;
&#xD;
         14. Use of soft drugs (such as marijuana) within three months prior to screening or hard&#xD;
             drugs such as crack, cocaine or heroin within one year prior to screening visit&#xD;
&#xD;
         15. Intake of any drugs known to induce or inhibit hepatic drug metabolism (examples of&#xD;
             inducers are barbiturates, carbamazepine, phenytoin, glucocorticoids,&#xD;
             rifampin/rifabutin; examples of inhibitors are, erythromycin, ketoconazole, indinavir,&#xD;
             cobicistat-containing products) within one month prior to administration of the study&#xD;
             medication. Under these circumstances, subject inclusion will be judged by the&#xD;
             principal investigator.&#xD;
&#xD;
         16. History of peptic ulcer, other gastrointestinal disorders (e.g. chronic diarrhoea,&#xD;
             irritable bowel syndrome) or unresolved gastrointestinal symptoms (e.g. diarrhea,&#xD;
             vomiting) or significant hepatic, renal or other condition that is known to interfere&#xD;
             with the absorption, distribution, metabolism or excretion of the drug.&#xD;
&#xD;
         17. Use of oral or parenteral corticosteroids in the previous four 4 weeks&#xD;
&#xD;
         18. Eye disorders especially Glaucoma (or a family history of glaucoma)&#xD;
&#xD;
         19. Use of prescription medication (within 14 days prior to the first administration of&#xD;
             study medication) or over-the-counter (OTC) products (including food supplements&#xD;
             vitamins and herbal supplements) within one week (7 days) prior to the first&#xD;
             administration of study medication, except for topical products without systematic&#xD;
             absorption. Contraceptives are allowed.&#xD;
&#xD;
         20. Vaccination for prophylaxis from seasonal flu or any other vaccination within seven&#xD;
             days prior to administration&#xD;
&#xD;
         21. History of allergy to any food, intolerance or special diet, that in the opinion of&#xD;
             the medical sub-investigator could contraindicate the subject's participation in the&#xD;
             study.&#xD;
&#xD;
         22. A depot injection or an implant of any drug (except hormonal contraceptives) within 3&#xD;
             months prior to treatment administration.&#xD;
&#xD;
         23. Donation of plasma (500 ml) within 7 days prior to treatment administration.&#xD;
&#xD;
         24. Donation of whole blood or loss of whole blood ≥ 500 ml prior to administration of the&#xD;
             study medication within 30 days prior to treatment administration.&#xD;
&#xD;
         25. Participation in another clinical trial simultaneously.&#xD;
&#xD;
         26. Subjects receiving special diet or having intolerance in any of the provided study&#xD;
             meals or refusing to eat the study meals&#xD;
&#xD;
         27. Application of tattoo or body piercing within 30 days prior to treatment&#xD;
             administration.&#xD;
&#xD;
         28. Non-tolerance to venipuncture.&#xD;
&#xD;
         29. Breastfeeding women.&#xD;
&#xD;
         30. Positive pregnancy test at screening&#xD;
&#xD;
         31. Females of reproductive age that had sexual intercourse with a non-sterile male&#xD;
             partner without protection within 14 days prior to drug administration&#xD;
&#xD;
        Reliable contraception methods are considered the following:&#xD;
&#xD;
          -  combined (estrogen and progestogen containing) hormonal contraception associated with&#xD;
             inhibition of ovulation: oral, intravaginal or transdermal&#xD;
&#xD;
          -  progestogen-only hormonal contraception associated with inhibition of ovulation oral,&#xD;
             implanable or injectable&#xD;
&#xD;
          -  intrauterine device (IUD)&#xD;
&#xD;
          -  intrauterine hormone-releasing system (IUS)&#xD;
&#xD;
          -  bilateral tubal occlusion&#xD;
&#xD;
          -  vasectomised partner&#xD;
&#xD;
          -  sexual abstinence&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ioannis Stefanidis, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Thessaly Department of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>BECRO Clinical Facility</name>
      <address>
        <city>Larissa</city>
        <state>Thessaly</state>
        <zip>41100</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>March 8, 2021</last_update_submitted>
  <last_update_submitted_qc>March 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>bioequivalence</keyword>
  <keyword>fluticasone propionate</keyword>
  <keyword>salmeterol xinafoate</keyword>
  <keyword>ADVAIR</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
    <mesh_term>Salmeterol Xinafoate</mesh_term>
    <mesh_term>Fluticasone-Salmeterol Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 12, 2021</submitted>
    <returned>July 2, 2021</returned>
  </pending_results>
  <!-- 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/NCT04466176
org study id: BECRO/RESP/BE250-PIVOTAL
nct id: NCT04466176
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Bioequivalence study between two inhaler products of fixed dose combination of fluticasone
      propionate and salmeterol xinafoate inhalation powder
A bioequivalence study of a single dose of the fixed-dose combination of fluticasone
      propionate and salmeterol xinafoate inhalation powder administered from Fluticasone
      propionate 250 mcg and Salmeterol xinafoate 50 mcg inhalation powder/Respirent
      Pharmaceuticals (test-Τ) as 2 inhalations and ADVAIR DISKUS® 250/50 mcg inhalation powder/GSK
      (reference-R) in healthy volunteers under fasting conditions. The study will be one-center
      crossover, randomized, 2-period, 2-sequence (RT and TR), single dose, laboratory-blinded.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: One-center crossover, randomized, 2-period, 2-sequence (RT and TR), single dose, laboratory-blinded study
primary purpose: Other
masking: Single (Outcomes Assessor)
masking description: laboratory-blinded
measure: Cmax
time frame: up to 36 hours post-administration
description: Maximum plasma concentration, it is read directly from the raw data
measure: AUC(0-t)
time frame: up to 36 hours post-administration
description: Area under the plasma concentration curve from time 0 to the last measured
measure: AUC0-∞
time frame: up to 36 hours post-administration
description: Area under the plasma concentration-time curve extrapolated to infinity
measure: Tmax
time frame: up to 36 hours post-administration
description: Time until Cmax is reached, it is read directly from the observed concentrations
measure: t1/2
time frame: up to 36 hours post-administration
description: Plasma concentration halflife, it is calculated from the ratio 0.693/λZ
measure: λz
time frame: up to 36 hours post-administration
description: Terminal elimination rate constant, calculated from the slope of the final phase of the ln-concentration curve versus time with regression analysis
measure: Residual area
time frame: up to 36 hours post-administration
description: [AUC(0-∞)-AUC(0-t)]/AUC(0-∞)]
arm group label: Test Product
arm group type: Experimental
description: Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals
arm group label: Reference Product
arm group type: Active Comparator
description: ADVAIR DISKUS® 250/50
intervention type: Drug
intervention name: Test Product
description: 2 inhalations of Test and Reference product in each study period
arm group label: Test Product
other name: Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals
intervention type: Drug
intervention name: Reference Product
description: 2 inhalations of Test and Reference product in each study period
arm group label: Reference Product
other name: ADVAIR DISKUS 250/50
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ioannis Stefanidis, Professor
role: Principal Investigator
affiliation: University of Thessaly Department of Medicine
facility: 
country: Greece
responsible party type: Sponsor
mesh term: Respiratory Aspiration
mesh term: Fluticasone
mesh term: Xhance
mesh term: Salmeterol Xinafoate
mesh term: Fluticasone-Salmeterol Drug Combination
sharing ipd: No
submitted: June 12, 2021
returned: July 2, 2021