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/NCT05968612</url>
    </required_header>
    <id_info>
      <org_study_id>QP586-01</org_study_id>
      <nct_id>NCT05968612</nct_id>
    </id_info>
    <brief_title>Bioequivalence and Food Effect Bioavailability Study of Lumacaftor Film-Coated Tablets</brief_title>
    <official_title>A Single-Dose, Bioequivalence and Food Effect Bioavailability Study in Healthy Volunteers Comparing the Commercial Lumacaftor 200 mg / Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) to the Lumacaftor 200 mg Film-Coated Tablet Formulation, and the Lumacaftor 200 mg Film-Coated Tablet Formulation in the Fasted to Fed State.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Qanatpharma Canada LTD</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Qanatpharma Canada 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>
        The objective of this study is to assess bioequivalence of lumacaftor from Lumacaftor 200 mg&#xD;
        Film-Coated Tablet Formulation (Qanatpharma) versus the reference commercial product,&#xD;
        Lumacaftor 200 mg /Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) in the fed&#xD;
        state, and food-effect bioavailability of Lumacaftor 200 mg Film-Coated Tablet Formulation&#xD;
        (Qanatpharma) in the fasted and fed state in healthy, non-smoking, male and non-pregnant&#xD;
        female volunteers, 18 to 55 years of age, inclusive.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This single-dose, randomized, double-blind, three-way crossover, three-period,&#xD;
        three-sequence, three-treatment, single-centre, bioequivalence and food-effect study will&#xD;
        compare lumacaftor from Lumacaftor 200 mg Film-Coated Tablet test formulation and the&#xD;
        commercial product, Lumacaftor 200 mg/Ivacaftor 125 mg Combination Film-Coated Tablet&#xD;
        (Orkambi®) under fed conditions, and food-effect bioavailability study of Lumacaftor 200 mg&#xD;
        Film-Coated Tablet test formulation from fasted to fed state.&#xD;
  &#xD;
        The products will be studied using a crossover design with 36 healthy, non-smoking male and&#xD;
        non-pregnant female volunteers being administered an oral dose of 1 x (2 x lumacaftor 200 mg)&#xD;
        under fasted and fed conditions and 1 x (2 x lumacaftor 200 mg/ ivacaftor 125 mg) under fed&#xD;
        conditions. There will be at least a 14-day washout period between the study periods to avoid&#xD;
        carry-over effects of the preceding treatments.&#xD;
  &#xD;
        This study is being conducted to support development of a lumacaftor mono-substance treatment&#xD;
        for improving cerebral blood flow.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">November 2023</completion_date>
    <primary_completion_date type="Anticipated">November 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>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>The maximal observed plasma concentration (Cmax)</measure>
      <time_frame>Up to 72 hours post dose in each treatment period</time_frame>
      <description>Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Area under the concentration-time curve from time zero to 72 hours (AUC72)</measure>
      <time_frame>Up to 72 hours post dose in each treatment period</time_frame>
      <description>Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Area under the concentration-time curve from time zero to infinity (AUCinf)</measure>
      <time_frame>Up to 72 hours post dose in each treatment period</time_frame>
      <description>Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time when the maximal plasma concentration is observed (Tmax)</measure>
      <time_frame>Up to 72 hours post dose in each treatment period</time_frame>
      <description>Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours</description>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Healthy Volunteer</condition>
    <arm_group>
      <arm_group_label>Treatment A (Test-Fed)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Following a 10-hour overnight fasting period, subjects will eat a high-fat, high-calorie breakfast, and 30 minutes later subjects will receive a single dose of 2 Lumacaftor 200 mg Film-Coated Tablets.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment B (Reference-Fed)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Following a 10-hour overnight fasting period, subjects will eat a high-fat, high-calorie breakfast, and 30 minutes later subjects will receive a single dose of 2 Lumacaftor 200 mg/Ivacaftor 125 mg Combination Film-Coated Tablets (Orkambi®)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment C (Test-Fasted)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Following a 10-hour overnight fasting period, subjects will receive a single dose of 2 Lumacaftor 200 mg Film-Coated Tablets.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lumacaftor 200 mg/Ivacaftor 125 mg Film-Coated Tablet</intervention_name>
      <description>Film-coated tablet administered orally.</description>
      <arm_group_label>Treatment B (Reference-Fed)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lumacaftor 200 mg Film-Coated Tablet Formulation</intervention_name>
      <description>Film-coated tablet administered orally.</description>
      <arm_group_label>Treatment A (Test-Fed)</arm_group_label>
      <arm_group_label>Treatment C (Test-Fasted)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Healthy, non-smoking male and non-pregnant female volunteers, 18 years to 55 years of&#xD;
               age, inclusive.&#xD;
  &#xD;
            2. Body mass index (BMI) that is between 18.5 and 30.0 kg/m^2, inclusive.&#xD;
  &#xD;
            3. Results of clinical laboratory tests are within the normal range or with a deviation&#xD;
               that is not considered clinically significant by the principal investigator.&#xD;
  &#xD;
            4. Ability to fast for at least 10 hours and consume a high-fat, high-calorie meal, as&#xD;
               well as standard meals.&#xD;
  &#xD;
            5. Agree not to have a tattoo or body piercing until the end of the study.&#xD;
  &#xD;
            6. Agree not to receive the COVID-19 vaccination from 7 days prior to the first study&#xD;
               drug dose until 7 days after the last study drug administration in the study.&#xD;
  &#xD;
            7. Female subjects of childbearing potential and males who are able to father children&#xD;
               must meet the criteria defined in the protocol.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known history or presence of any clinically significant diseases or conditions unless&#xD;
               determined as not clinically significant by the Investigator.&#xD;
  &#xD;
            2. Presence of any clinically significant illness within 30 days prior to first dosing,&#xD;
               as determined by the Investigator.&#xD;
  &#xD;
            3. Presence of any significant physical or organ abnormality as determined by the&#xD;
               Investigator.&#xD;
  &#xD;
            4. A positive test result for any of the following: HIV, Hepatitis B surface antigen,&#xD;
               Hepatitis C, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates,&#xD;
               phencyclidine and benzodiazepines), alcohol breath test and cotinine. Positive&#xD;
               pregnancy test for female subjects.&#xD;
  &#xD;
            5. Known history or presence of:&#xD;
  &#xD;
                 -  Alcohol abuse or dependence within one year prior to first drug administration;&#xD;
  &#xD;
                 -  Drug abuse or dependence;&#xD;
  &#xD;
                 -  Hypersensitivity or idiosyncratic reaction to lumacaftor and ivacaftor, its&#xD;
                    excipients, and/or related substances;&#xD;
  &#xD;
                 -  Food allergies&#xD;
  &#xD;
                 -  Presence of any dietary restrictions unless deemed by the Investigator as &quot;Not&#xD;
                    Clinically Significant&quot;.&#xD;
  &#xD;
                 -  Severe allergic reactions (e.g. anaphylactic reactions, angioedema).&#xD;
  &#xD;
            6. Intolerance to and/or difficulty with blood sampling through venipuncture.&#xD;
  &#xD;
            7. Abnormal diet patterns (for any reason) during the four weeks preceding the study,&#xD;
               including fasting, high protein diets, etc.&#xD;
  &#xD;
            8. Individuals who have donated, in the days prior to first study drug administration:&#xD;
  &#xD;
                 -  50-499 mL of blood in the previous 30 days;&#xD;
  &#xD;
                 -  500 mL or more in the previous 56 days.&#xD;
  &#xD;
            9. Donation of plasma by plasmapheresis within 7 days prior to first study drug&#xD;
               administration.&#xD;
  &#xD;
           10. Individuals who have participated in another clinical trial or who received an&#xD;
               investigational drug within 30 days prior to first study drug administration.&#xD;
  &#xD;
           11. Females having used implanted, injected, intravaginal, or intrauterine hormonal&#xD;
               contraceptive within 6 months prior to first study drug administration.&#xD;
  &#xD;
           12. Females taking oral or transdermal hormonal contraceptives within 30 days prior to&#xD;
               first study drug administration.&#xD;
  &#xD;
           13. Use of any enzyme-modifying drugs or products in the previous 30 days before first&#xD;
               study drug administration.&#xD;
  &#xD;
           14. Use of any prescription medication within 14 days prior to first study drug&#xD;
               administration (except medically acceptable contraceptive products).&#xD;
  &#xD;
           15. Use of any over-the-counter medications within 14 days prior to first study drug&#xD;
               administration (except for medically acceptable contraceptive products).&#xD;
  &#xD;
           16. Consumption of food or beverages containing grapefruit and/or pomelo within 10 days&#xD;
               prior to first study drug administration.&#xD;
  &#xD;
           17. Consumption of food or beverages containing caffeine/methylxanthines, poppy seeds&#xD;
               and/or alcohol within 48 hours before dosing.&#xD;
  &#xD;
           18. Individuals having undergone any major surgery within 6 months prior to the start of&#xD;
               the study, unless deemed otherwise by Investigator.&#xD;
  &#xD;
           19. Difficulty with swallowing whole film-coated tablet.&#xD;
  &#xD;
           20. Women who are pregnant or lactating.&#xD;
  &#xD;
           21. Have had a tattoo or body piercing within 30 days prior to first study drug&#xD;
               administration.&#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>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 21, 2023</last_update_submitted>
    <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>lumacaftor</keyword>
    <keyword>cystic fibrosis transmembrane regulator-corrector</keyword>
    <keyword>CFTR-corrector</keyword>
    <keyword>food effect</keyword>
    <keyword>healthy volunteers</keyword>
    <keyword>cerebral blood flow</keyword>
    <keyword>CBF</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ivacaftor</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Qanatpharma will provide access upon request to individual de-identified participant data reported in the publication beginning 12 months after publication and for up to 36 months following article publication. Data sharing requests can be made by qualified researchers for approved proposals under the terms of a Data Use Agreement. Contact information will be provided at the time of article publication.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>12 months after article publication and for up to 36 months following article publication</ipd_time_frame>
      <ipd_access_criteria>Data sharing requests can be made by qualified researchers for approved proposals under the terms of a Data Use Agreement.</ipd_access_criteria>
    </patient_data>
    <!-- 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/NCT05968612
  org study id: QP586-01
  nct id: NCT05968612
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The objective of this study is to assess bioequivalence of lumacaftor from Lumacaftor 200 mg
        Film-Coated Tablet Formulation (Qanatpharma) versus the reference commercial product,
        Lumacaftor 200 mg /Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) in the fed
        state, and food-effect bioavailability of Lumacaftor 200 mg Film-Coated Tablet Formulation
        (Qanatpharma) in the fasted and fed state in healthy, non-smoking, male and non-pregnant
        female volunteers, 18 to 55 years of age, inclusive.
  This single-dose, randomized, double-blind, three-way crossover, three-period,
        three-sequence, three-treatment, single-centre, bioequivalence and food-effect study will
        compare lumacaftor from Lumacaftor 200 mg Film-Coated Tablet test formulation and the
        commercial product, Lumacaftor 200 mg/Ivacaftor 125 mg Combination Film-Coated Tablet
        (Orkambi®) under fed conditions, and food-effect bioavailability study of Lumacaftor 200 mg
        Film-Coated Tablet test formulation from fasted to fed state.
  
        The products will be studied using a crossover design with 36 healthy, non-smoking male and
        non-pregnant female volunteers being administered an oral dose of 1 x (2 x lumacaftor 200 mg)
        under fasted and fed conditions and 1 x (2 x lumacaftor 200 mg/ ivacaftor 125 mg) under fed
        conditions. There will be at least a 14-day washout period between the study periods to avoid
        carry-over effects of the preceding treatments.
  
        This study is being conducted to support development of a lumacaftor mono-substance treatment
        for improving cerebral blood flow.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  measure: The maximal observed plasma concentration (Cmax)
  time frame: Up to 72 hours post dose in each treatment period
  description: Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
  measure: Area under the concentration-time curve from time zero to 72 hours (AUC72)
  time frame: Up to 72 hours post dose in each treatment period
  description: Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
  measure: Area under the concentration-time curve from time zero to infinity (AUCinf)
  time frame: Up to 72 hours post dose in each treatment period
  description: Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
  measure: Time when the maximal plasma concentration is observed (Tmax)
  time frame: Up to 72 hours post dose in each treatment period
  description: Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
  arm group label: Treatment A (Test-Fed)
  arm group type: Experimental
  description: Following a 10-hour overnight fasting period, subjects will eat a high-fat, high-calorie breakfast, and 30 minutes later subjects will receive a single dose of 2 Lumacaftor 200 mg Film-Coated Tablets.
  arm group label: Treatment B (Reference-Fed)
  arm group type: Active Comparator
  description: Following a 10-hour overnight fasting period, subjects will eat a high-fat, high-calorie breakfast, and 30 minutes later subjects will receive a single dose of 2 Lumacaftor 200 mg/Ivacaftor 125 mg Combination Film-Coated Tablets (Orkambi®)
  arm group label: Treatment C (Test-Fasted)
  arm group type: Experimental
  description: Following a 10-hour overnight fasting period, subjects will receive a single dose of 2 Lumacaftor 200 mg Film-Coated Tablets.
  intervention type: Drug
  intervention name: Lumacaftor 200 mg/Ivacaftor 125 mg Film-Coated Tablet
  description: Film-coated tablet administered orally.
  arm group label: Treatment B (Reference-Fed)
  intervention type: Drug
  intervention name: Lumacaftor 200 mg Film-Coated Tablet Formulation
  description: Film-coated tablet administered orally.
  arm group label: Treatment A (Test-Fed)
  arm group label: Treatment C (Test-Fasted)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 55 Years
  healthy volunteers: Accepts Healthy Volunteers
  responsible party type: Sponsor
  mesh term: Ivacaftor
  sharing ipd: Yes
  ipd description: Qanatpharma will provide access upon request to individual de-identified participant data reported in the publication beginning 12 months after publication and for up to 36 months following article publication. Data sharing requests can be made by qualified researchers for approved proposals under the terms of a Data Use Agreement. Contact information will be provided at the time of article publication.
  ipd info type: Study Protocol
  ipd time frame: 12 months after article publication and for up to 36 months following article publication
  ipd access criteria: Data sharing requests can be made by qualified researchers for approved proposals under the terms of a Data Use Agreement.