<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/NCT03772223</url>
  </required_header>
  <id_info>
    <org_study_id>D6930C00003</org_study_id>
    <nct_id>NCT03772223</nct_id>
  </id_info>
  <brief_title>A Study to Compare the Pharmacokinetics of Budesonide and Albuterol Delivered by PT027 Compared With PT007 and PT008 Administered Separately.</brief_title>
  <official_title>A Phase 1, Randomized, Open-label, Single-dose, 3-way Cross-over Study to Compare the Pharmacokinetics of Budesonide and Albuterol Delivered by PT027 Compared With PT007 and PT008 Administered Separately (LOGAN).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</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>
      This is a Phase 1 study to compare the pharmacokinetics of budesonide and albuterol delivered&#xD;
      by PT027 compared with PT007 and PT008 administered separately.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be a randomized, 3-way cross-over study in healthy male and female&#xD;
      participants, performed at a single study centre. A total of 90 healthy male or female&#xD;
      participants will be randomized in this study to ensure that at least 81 participants are&#xD;
      evaluable.&#xD;
&#xD;
      The study will comprise:&#xD;
&#xD;
      A screening period of maximum 27 days; Three treatment periods during which participants will&#xD;
      be resident from the morning before dosing with Budesonide/Albuterol Sulfate metered dose&#xD;
      inhaler (BDA MDI), Budesonide metered dose inhaler (BD MDI), and Albuterol Sulfate metered&#xD;
      dose inhaler (AS MDI [Day -1]) until at least 24 hours after dosing; discharged on the&#xD;
      morning of Day 2; and A final visit within 5 to 7 days after the last administration of BDA&#xD;
      MDI, BD MDI, or AS MDI.&#xD;
&#xD;
      There will be a minimum washout period of 7 days between each dose administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Actual">May 10, 2019</completion_date>
  <primary_completion_date type="Actual">May 10, 2019</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the area under the plasma concentration-time curve from time zero to infinity (AUC) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the AUC after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t) for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUC([0-t]) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t) for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the AUC(0-t) after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine observed maximum plasma concentration (Cmax) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine Cmax after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>tlast for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the time of last quantifiable plasma concentration (tlast) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tlast for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the tlast after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine time to reach maximum observed plasma concentration (tmax) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine tmax after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2λz for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the time to apparent elimination half-life (t1/2λz)after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2λz for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine t1/2λz after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the terminal elimination rate constant (λz) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the λz after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the apparent total body clearance of drug from plasma after extravascular administration (CL/F) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the CL/F after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F for albuterol</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F for budesonide</measure>
    <time_frame>At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)</time_frame>
    <description>To determine the Vz/F after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events (AEs)/serious AEs (SAEs)</measure>
    <time_frame>From Screening to Post-study Visit (5-7 days)</time_frame>
    <description>To assess the safety and tolerability of BDA MDI, BD MDI, and AS MDI.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">91</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Treatment sequence 1 (ABC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027) , Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), and Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence 2 (BCA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence 3 (CBA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence 4 (ACB)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027), Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), and Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence 5 (BAC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027), and Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence 6 (CAB)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027), and Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)</intervention_name>
    <description>Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).</description>
    <arm_group_label>Treatment sequence 1 (ABC)</arm_group_label>
    <arm_group_label>Treatment sequence 2 (BCA)</arm_group_label>
    <arm_group_label>Treatment sequence 3 (CBA)</arm_group_label>
    <arm_group_label>Treatment sequence 4 (ACB)</arm_group_label>
    <arm_group_label>Treatment sequence 5 (BAC)</arm_group_label>
    <arm_group_label>Treatment sequence 6 (CAB)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment B (Budesonide metered dose inhaler)</intervention_name>
    <description>Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).</description>
    <arm_group_label>Treatment sequence 1 (ABC)</arm_group_label>
    <arm_group_label>Treatment sequence 2 (BCA)</arm_group_label>
    <arm_group_label>Treatment sequence 3 (CBA)</arm_group_label>
    <arm_group_label>Treatment sequence 4 (ACB)</arm_group_label>
    <arm_group_label>Treatment sequence 5 (BAC)</arm_group_label>
    <arm_group_label>Treatment sequence 6 (CAB)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment C (Albuterol Sulfate metered dose inhaler)</intervention_name>
    <description>Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).</description>
    <arm_group_label>Treatment sequence 1 (ABC)</arm_group_label>
    <arm_group_label>Treatment sequence 2 (BCA)</arm_group_label>
    <arm_group_label>Treatment sequence 3 (CBA)</arm_group_label>
    <arm_group_label>Treatment sequence 4 (ACB)</arm_group_label>
    <arm_group_label>Treatment sequence 5 (BAC)</arm_group_label>
    <arm_group_label>Treatment sequence 6 (CAB)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of signed and dated, written informed consent prior to any study specific&#xD;
             procedures.&#xD;
&#xD;
          2. Healthy male and female participants aged 18 to 55 years (inclusive) with suitable&#xD;
             veins for cannulation or repeated venipuncture.&#xD;
&#xD;
          3. Females must have a negative pregnancy test at the Screening Visit and on admission to&#xD;
             the Clinical Unit and must not be lactating.&#xD;
&#xD;
          4. Have a body mass index between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and&#xD;
             no more than 100 kg inclusive.&#xD;
&#xD;
          5. Must be able to demonstrate proper inhalation technique using the AIM device and&#xD;
             placebo MDI at the Screening Visit.&#xD;
&#xD;
          6. Forced expiratory volume in 1 second in litres (FEV1) ≥ 80% of predicted value and&#xD;
             forced vital capacity in litres (FEV1)/FVC ratio ≥ 70%.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or nursing female participants or participants who are trying to conceive.&#xD;
&#xD;
          2. For female participants, a positive serum human chorionic gonadotropin (hCG) test at&#xD;
             screening or a positive urine hCG at admission for any of the 3 Treatment Periods.&#xD;
&#xD;
          3. History of any clinically significant disease or disorder which, in the opinion of the&#xD;
             Principal Investigator (PI), may either put the subject at risk because of&#xD;
             participation in the study, or influence the results or the participant's ability to&#xD;
             participate in the study.&#xD;
&#xD;
          4. History or presence of gastrointestinal, hepatic or renal disease, or any other&#xD;
             condition known to interfere with absorption, distribution, metabolism, or excretion&#xD;
             of drugs.&#xD;
&#xD;
          5. Participants who have cancer that has not been in complete remission for at least 5&#xD;
             years.&#xD;
&#xD;
          6. Any history of asthma or Chronic obstructive pulmonary disease.&#xD;
&#xD;
          7. Any clinically significant illness, medical/surgical procedure, or trauma within 4&#xD;
             weeks of the first administration of Investigational Medicinal Product (IMP).&#xD;
&#xD;
          8. Any clinically significant abnormalities in clinical chemistry, haematology, or&#xD;
             urinalysis results, at the Screening Visit as judged by the PI.&#xD;
&#xD;
          9. Any clinically significant abnormal findings in vital signs at the Screening Visit, as&#xD;
             judged by the PI.&#xD;
&#xD;
         10. Any clinically significant abnormalities on 12-lead electrocardiogram at the Screening&#xD;
             Visit, as judged by the PI.&#xD;
&#xD;
         11. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C&#xD;
             antibody, and human immunodeficiency virus antibody.&#xD;
&#xD;
         12. Known or suspected history of drug abuse in the past 2 years, as judged by the PI.&#xD;
&#xD;
         13. Has received another new chemical entity (defined as a compound which has not been&#xD;
             approved for marketing) within 3 months of the first administration of IMP in this&#xD;
             study. The period of exclusion begins 3 months after the final dose or 1 month after&#xD;
             the last visit whichever is the longest.&#xD;
&#xD;
         14. Plasma donation within 1 month of screening or any blood donation/loss more than 500&#xD;
             mL during the 3 months prior to screening.&#xD;
&#xD;
         15. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as&#xD;
             judged by the PI or history of hypersensitivity to drugs with a similar chemical&#xD;
             structure or class to budesonide and albuterol sulfate.&#xD;
&#xD;
         16. Current smokers or those who have smoked or used nicotine products (including e&#xD;
             cigarettes) within the 3 months prior to screening.&#xD;
&#xD;
         17. Positive screen for drugs of abuse, cotinine or alcohol at the Screening Visit or on&#xD;
             each admission to the Clinical Unit.&#xD;
&#xD;
         18. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks&#xD;
             prior to the first administration of IMP.&#xD;
&#xD;
         19. Use of any prescribed or non prescribed medication including antacids, analgesics&#xD;
             (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of&#xD;
             20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to&#xD;
             the first administration of IMP or longer if the medication has a long half life.&#xD;
&#xD;
         20. Known or suspected history of alcohol or excessive intake of alcohol in the last 2&#xD;
             years as judged by the PI.&#xD;
&#xD;
         21. Involvement of any AstraZeneca, PAREXEL or study site employee or their close&#xD;
             relatives.&#xD;
&#xD;
         22. Judgment by the PI that the participant should not participate in the study if they&#xD;
             have any ongoing or recent (i.e., during the screening period) minor medical&#xD;
             complaints that may interfere with the interpretation of study data or are considered&#xD;
             unlikely to comply with study procedures, restrictions, and requirements.&#xD;
&#xD;
         23. Vulnerable participant, e.g., kept in detention, protected adults under guardianship,&#xD;
             trusteeship, or committed to an institution by governmental or juridical order.&#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>Pablo Forte Soto</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parexel</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>May 19, 2019</last_update_submitted>
  <last_update_submitted_qc>May 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinectics</keyword>
  <keyword>Inhaled corticosteroid</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Budesonide</mesh_term>
    <mesh_term>Albuterol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03772223
org study id: D6930C00003
nct id: NCT03772223
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a Phase 1 study to compare the pharmacokinetics of budesonide and albuterol delivered
      by PT027 compared with PT007 and PT008 administered separately.
This study will be a randomized, 3-way cross-over study in healthy male and female
      participants, performed at a single study centre. A total of 90 healthy male or female
      participants will be randomized in this study to ensure that at least 81 participants are
      evaluable.

      The study will comprise:

      A screening period of maximum 27 days; Three treatment periods during which participants will
      be resident from the morning before dosing with Budesonide/Albuterol Sulfate metered dose
      inhaler (BDA MDI), Budesonide metered dose inhaler (BD MDI), and Albuterol Sulfate metered
      dose inhaler (AS MDI [Day -1]) until at least 24 hours after dosing; discharged on the
      morning of Day 2; and A final visit within 5 to 7 days after the last administration of BDA
      MDI, BD MDI, or AS MDI.

      There will be a minimum washout period of 7 days between each dose administration.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the area under the plasma concentration-time curve from time zero to infinity (AUC) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: AUC for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the AUC after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: AUC(0-t) for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUC([0-t]) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: AUC(0-t) for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the AUC(0-t) after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: Cmax for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine observed maximum plasma concentration (Cmax) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: Cmax for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine Cmax after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: tlast for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the time of last quantifiable plasma concentration (tlast) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: tlast for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the tlast after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: tmax for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine time to reach maximum observed plasma concentration (tmax) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: tmax for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine tmax after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: t1/2λz for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the time to apparent elimination half-life (t1/2λz)after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy
measure: t1/2λz for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine t1/2λz after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: λz for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the terminal elimination rate constant (λz) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: λz for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the λz after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: CL/F for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the apparent total body clearance of drug from plasma after extravascular administration (CL/F) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: CL/F for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the CL/F after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: Vz/F for albuterol
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: Vz/F for budesonide
time frame: At Day 1 (pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose), and Day 2 (24 hours post dose)
description: To determine the Vz/F after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
measure: Number of participants with adverse events (AEs)/serious AEs (SAEs)
time frame: From Screening to Post-study Visit (5-7 days)
description: To assess the safety and tolerability of BDA MDI, BD MDI, and AS MDI.
arm group label: Treatment sequence 1 (ABC)
arm group type: Experimental
description: Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027) , Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), and Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
arm group label: Treatment sequence 2 (BCA)
arm group type: Experimental
description: Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
arm group label: Treatment sequence 3 (CBA)
arm group type: Experimental
description: Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
arm group label: Treatment sequence 4 (ACB)
arm group type: Experimental
description: Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027), Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), and Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
arm group label: Treatment sequence 5 (BAC)
arm group type: Experimental
description: Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027), and Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
arm group label: Treatment sequence 6 (CAB)
arm group type: Experimental
description: Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler [AS MDI] - PT007), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler [BDA MDI] - PT027), and Treatment B (Budesonide metered dose inhaler [BD MDI] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
intervention type: Drug
intervention name: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
description: Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).
arm group label: Treatment sequence 1 (ABC)
arm group label: Treatment sequence 2 (BCA)
arm group label: Treatment sequence 3 (CBA)
arm group label: Treatment sequence 4 (ACB)
arm group label: Treatment sequence 5 (BAC)
arm group label: Treatment sequence 6 (CAB)
intervention type: Drug
intervention name: Treatment B (Budesonide metered dose inhaler)
description: Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).
arm group label: Treatment sequence 1 (ABC)
arm group label: Treatment sequence 2 (BCA)
arm group label: Treatment sequence 3 (CBA)
arm group label: Treatment sequence 4 (ACB)
arm group label: Treatment sequence 5 (BAC)
arm group label: Treatment sequence 6 (CAB)
intervention type: Drug
intervention name: Treatment C (Albuterol Sulfate metered dose inhaler)
description: Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).
arm group label: Treatment sequence 1 (ABC)
arm group label: Treatment sequence 2 (BCA)
arm group label: Treatment sequence 3 (CBA)
arm group label: Treatment sequence 4 (ACB)
arm group label: Treatment sequence 5 (BAC)
arm group label: Treatment sequence 6 (CAB)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pablo Forte Soto
role: Principal Investigator
affiliation: Parexel
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Budesonide
mesh term: Albuterol
sharing ipd: Undecided