xml: <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/NCT05982990</url>
    </required_header>
    <id_info>
      <org_study_id>BECRO/RESP/AEROPK250</org_study_id>
      <nct_id>NCT05982990</nct_id>
    </id_info>
    <brief_title>Bioequivalence Study for Fluticasone Propionate 250 mcg/Salmeterol Xinafoate 50 mcg Inhalation Powder in Healthy Volunteers</brief_title>
    <official_title>A 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>Active, not recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">November 20, 2023</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2023</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 for Fluticasone Propionate (FP)</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>Cmax for Salmeterol</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>(AUC0-t) for Fluticasone Propionate (FP)</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>
    <primary_outcome>
      <measure>AUC0-t for Salmeterol</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>Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Test</description>
    </arm_group>
    <arm_group>
      <arm_group_label>ADVAIR DISKUS® 250/50</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Reference</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals</intervention_name>
      <description>2 inhalations in one study period</description>
      <arm_group_label>Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals</arm_group_label>
      <other_name>Test</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ADVAIR DISKUS® 250/50</intervention_name>
      <description>2 inhalations in one study period</description>
      <arm_group_label>ADVAIR DISKUS® 250/50</arm_group_label>
      <other_name>Reference</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 unable to gestate [i.e.&#xD;
               post-menopausal (absence of menses for 12 months prior to drug administration),&#xD;
               hysterectomy, bilateral oophorectomy, tubal ligation at least 6 months prior to drug&#xD;
               administration] or at reproductive age; Females of reproductive age if sexually&#xD;
               active, must be practicing an effective method of birth control within 14 days prior&#xD;
               to the first drug administration and throughout the study.&#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 progestogen-only hormonal&#xD;
               contraception associated with inhibition of ovulation oral, implantable or injectable&#xD;
               intrauterine device (IUD) intrauterine hormone-releasing system (IUS) bilateral tubal&#xD;
               occlusion vasectomised partner sexual abstinence&#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;
        </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>Chrysoula Doxani, MD, MSc, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Becro Ltd.</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>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</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>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05982990
  org study id: BECRO/RESP/AEROPK250
  nct id: NCT05982990
  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 for Fluticasone Propionate (FP)
  time frame: up to 36 hours post-administration
  description: Maximum plasma concentration, it is read directly from the raw data
  measure: Cmax for Salmeterol
  time frame: up to 36 hours post-administration
  description: Maximum plasma concentration, it is read directly from the raw data
  measure: (AUC0-t) for Fluticasone Propionate (FP)
  time frame: up to 36 hours post-administration
  description: Area under the plasma concentration curve from time 0 to the last measured
  measure: AUC0-t for Salmeterol
  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: Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals
  arm group type: Experimental
  description: Test
  arm group label: ADVAIR DISKUS® 250/50
  arm group type: Active Comparator
  description: Reference
  intervention type: Drug
  intervention name: Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals
  description: 2 inhalations in one study period
  arm group label: Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals
  other name: Test
  intervention type: Drug
  intervention name: ADVAIR DISKUS® 250/50
  description: 2 inhalations in one study period
  arm group label: ADVAIR DISKUS® 250/50
  other name: Reference
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Chrysoula Doxani, MD, MSc, PhD
  role: Principal Investigator
  affiliation: Becro Ltd.
  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