<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/NCT04494321</url>
  </required_header>
  <id_info>
    <org_study_id>MCPE15003M4</org_study_id>
    <nct_id>NCT04494321</nct_id>
  </id_info>
  <brief_title>A Bioequivalence Pivotal Study of SYN010 HFA Inhaler and Symbicort® 160/4.5 in Healthy Volunteers Without Charcoal Block</brief_title>
  <official_title>A Single-Dose, Randomized, Open-Label, Two-Treatment, Three-Period, Three-Sequence, Three-Way Crossover, Partial Replicate, Oral BE Pivotal Study of SYN010 HFA 160/4.5 Inhaler and Symbicort® 160/4.5 in Healthy Volunteers Without Charcoal Block</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Intech Biopharm Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Intech Biopharm Ltd.</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this pivotal study is to evaluate the relative bioavailability of SYN010 HFA&#xD;
      Inhaler and Symbicort 160/4.5μg in healthy volunteers without charcoal block.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A pivotal, single-dose, randomized, open-label, partial replicate, three-period,&#xD;
      three-sequence, two-treatment, three-way crossover, comparative bioavailability study.&#xD;
&#xD;
      Ninety-nine, male and female volunteers, 20-45 years of age, with a body mass index (BMI)&#xD;
      within 18.5-30.0 kg/m2, inclusive, will be enrolled. (The body weight should be over 50 kg,&#xD;
      inclusive, respectively)&#xD;
&#xD;
      A single dose of 8 puffs (eq. to budesonide 1280 μg /formoterol fumarate dihydrate 36 μg) in&#xD;
      each study period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 19, 2017</start_date>
  <completion_date type="Actual">November 17, 2017</completion_date>
  <primary_completion_date type="Actual">November 17, 2017</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>Area Under Curve (AUC)</measure>
    <time_frame>Pre-dose and at 0.03, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24 and 36 hours after dosing.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>Pre-dose and at 0.03, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24 and 36 hours after dosing.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to reach Maximum plasma concentration (Tmax)</measure>
    <time_frame>Pre-dose and at 0.03, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24 and 36 hours after dosing.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure (BP)</measure>
    <time_frame>Pre-dose and at 0.5, 16, 24 and 36 hours after dosing.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body temperature (BT)</measure>
    <time_frame>Pre-dose and at 0.5, 16, 24 and 36 hours after dosing.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse rate (PR)</measure>
    <time_frame>Pre-dose and at 0.5, 16, 24 and 36 hours after dosing.</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">99</enrollment>
  <condition>Asthma</condition>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>Reference 1 Symbicort Inhaler 160/4.5μg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Reference 1: Symbicort Inhaler (Budesonide/ Formoterol, 160/4.5μg), Single dose, 8 puffs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SYN010 HFA Inhaler</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SYN010 HFA (Budesonide/ Formoterol, 160/4.5μg), Single dose, 8 puffs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference 2 Symbicort Inhaler 160/4.5μg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Reference 2: Symbicort Inhaler (Budesonide/ Formoterol, 160/4.5μg), Single dose, 8 puffs</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Budesonide</intervention_name>
    <description>Inhaled corticosteroid</description>
    <arm_group_label>Reference 1 Symbicort Inhaler 160/4.5μg</arm_group_label>
    <arm_group_label>Reference 2 Symbicort Inhaler 160/4.5μg</arm_group_label>
    <arm_group_label>SYN010 HFA Inhaler</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Formoterol</intervention_name>
    <description>Long Acting Beta Agonist (LABA)</description>
    <arm_group_label>Reference 1 Symbicort Inhaler 160/4.5μg</arm_group_label>
    <arm_group_label>Reference 2 Symbicort Inhaler 160/4.5μg</arm_group_label>
    <arm_group_label>SYN010 HFA Inhaler</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male and female volunteers, aged 20-45, inclusive.&#xD;
&#xD;
          2. BMI that is within 18.5-30.0 kg/m², inclusive. (The body weight should be over 50 kg,&#xD;
             inclusive, respectively)&#xD;
&#xD;
          3. Healthy or Non Clinical Significant, according to the medical history,&#xD;
             Electrocardiography (ECG), Chest X-ray and physical examination as determined by the&#xD;
             Principal Investigator/Sub-Investigator.&#xD;
&#xD;
          4. Systolic blood pressure between 90-139 mmHg, inclusive, and diastolic blood pressure&#xD;
             between 50-90 mmHg, inclusive, and pulse rate between 50-100 bpm, inclusive and&#xD;
             temperature between 35.0-37.4°C.&#xD;
&#xD;
          5. Clinical laboratory values within reference range or Non-Clinical Significance (NCS)&#xD;
             judged by the Principal Investigator/Sub-Investigator.&#xD;
&#xD;
          6. Ability to comprehend and be informed of the nature of the study. Capable of giving&#xD;
             written informed consent prior to receiving any study medication. Must be able to&#xD;
             communicate effectively with clinic staff.&#xD;
&#xD;
          7. Ability to fast for at least 14 hours and to consume standard meals.&#xD;
&#xD;
          8. Availability to volunteer for the entire study duration and willing to adhere to all&#xD;
             protocol requirements.&#xD;
&#xD;
          9. Agree not to have a tattoo or body piercing until the end of the study.&#xD;
&#xD;
         10. Female subjects must fulfill at least one of the following:&#xD;
&#xD;
               1. Be surgically sterile for a minimum of 6 months;&#xD;
&#xD;
               2. Post-menopausal for a minimum of 1 year;&#xD;
&#xD;
               3. Agree to avoid pregnancy and use medically acceptable method of contraception&#xD;
                  from screening day until 30 days after study has ended (last study procedure).&#xD;
                  Medically acceptable methods of contraception include non-hormonal intrauterine&#xD;
                  device or double barrier method (condom with foam or vaginal spermicidal&#xD;
                  suppository, diaphragm with spermicide). Complete abstinence alone can be used as&#xD;
                  a method of contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known history or presence of any clinically significant hepatic (e.g. active liver&#xD;
             disease, hepatic impairment), renal/genitourinary (e.g. renal impairment),&#xD;
             gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine (e.g.&#xD;
             hypothyroidism), immunological, musculoskeletal (e.g. myopathy, rhabdomyolysis),&#xD;
             neurological, psychiatric, dermatological or hematological disease or condition unless&#xD;
             determined as not clinically significant by the Principal&#xD;
             Investigator/Sub-Investigator.&#xD;
&#xD;
          2. Clinically significant history or presence of any clinically significant&#xD;
             gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel disease),&#xD;
             unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), or other conditions&#xD;
             known to interfere with the absorption, distribution, metabolism or excretion of the&#xD;
             drug experienced within 7 days prior to first drug administration, as determined by&#xD;
             the Principal Investigator/Sub- Investigator.&#xD;
&#xD;
          3. Presence of any clinically significant illness within 30 days prior to first dosing,&#xD;
             as determined by the Principal Investigator/Sub-Investigator.&#xD;
&#xD;
          4. Presence of any significant physical or organ abnormality as determined by the&#xD;
             Principal Investigator/Sub-Investigator.&#xD;
&#xD;
          5. A positive test result for any of the following: Human immunodeficiency virus (HIV),&#xD;
             Hepatitis B surface antigen, Hepatitis C, drugs of abuse (amphetamines, barbiturates,&#xD;
             benzodiazepines, cocaine, opiates, phencyclidine, tetrahydrocannabinol), breath&#xD;
             alcohol test. Positive pregnancy test for female subjects.&#xD;
&#xD;
          6. Known history or presence of:&#xD;
&#xD;
               1. Alcohol abuse or dependence within one year prior to first drug administration;&#xD;
&#xD;
               2. Drug abuse or dependence;&#xD;
&#xD;
               3. Hypersensitivity or idiosyncratic reaction to budesonide, formoterol fumarate&#xD;
                  dihydrate , its excipients, and/or related substances;&#xD;
&#xD;
               4. Food allergies and/or presence of any dietary restrictions;&#xD;
&#xD;
               5. Severe allergic reactions (e.g. anaphylactic reactions, angioedema).&#xD;
&#xD;
          7. Intolerance to and/or difficulty with blood sampling through venipuncture.&#xD;
&#xD;
          8. Abnormal diet patterns (for any reason) during the four weeks preceding the study,&#xD;
             including fasting, high protein diets etc.&#xD;
&#xD;
          9. Individuals who have donated, in the days prior to first drug administration:&#xD;
&#xD;
               1. Less than 250 mL of blood in the previous 60 days&#xD;
&#xD;
               2. 300 mL or more in the previous 90 days&#xD;
&#xD;
         10. Donation of plasma by plasmapheresis within 7 days prior to first drug administration.&#xD;
&#xD;
         11. Individuals who have participated in another clinical trial and received an&#xD;
             investigational drug within 30 days prior to first drug administration.&#xD;
&#xD;
         12. Consumption of food or beverages containing caffeine/methylxanthines, poppy seeds&#xD;
             and/or alcohol within 48 hours before dosing and containing grapefruit and/or pomelo&#xD;
             within 10 days prior to first drug administration.&#xD;
&#xD;
         13. Use of any prescription medication within 30 days prior to first drug administration.&#xD;
&#xD;
         14. Use of any over-the-counter medications (including oral multivitamins, herbal and/or&#xD;
             dietary supplements) within 30 days prior to first drug administration (except for&#xD;
             spermicidal/barrier contraceptive products).&#xD;
&#xD;
         15. Females taking oral or transdermal hormonal contraceptives within 30 days prior to&#xD;
             first drug administration.&#xD;
&#xD;
         16. Females having used implanted, injected, intravaginal, or intrauterine hormonal&#xD;
             contraceptive within 6 months prior to first drug administration.&#xD;
&#xD;
         17. Individuals having undergone any major surgery within 6 months prior to the start of&#xD;
             the study, unless deemed otherwise by Principal Investigator/Sub-Investigator.&#xD;
&#xD;
         18. Known history of smoking or using tobacco products, nicotine products (patches, gum&#xD;
             etc.) within 6 months prior to first drug administration.&#xD;
&#xD;
         19. Pregnant/lactating women.&#xD;
&#xD;
         20. Subjects will be given training to ensure that subjects are able to correctly use the&#xD;
             investigational products in screening. The subjects who are unable to operate the&#xD;
             investigational products proficiently will not be included in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wen-Kuei Chang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Pharmacology Unit of Mackay Memorial Hospital Tamshui Branch</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Pharmacology Unit of Mackay Memorial Hospital Tamshui Branch</name>
      <address>
        <city>New Taipei City</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>July 28, 2020</last_update_submitted>
  <last_update_submitted_qc>July 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Budesonide</mesh_term>
    <mesh_term>Formoterol Fumarate</mesh_term>
  </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/NCT04494321
org study id: MCPE15003M4
nct id: NCT04494321
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The objective of this pivotal study is to evaluate the relative bioavailability of SYN010 HFA
      Inhaler and Symbicort 160/4.5μg in healthy volunteers without charcoal block.
A pivotal, single-dose, randomized, open-label, partial replicate, three-period,
      three-sequence, two-treatment, three-way crossover, comparative bioavailability study.

      Ninety-nine, male and female volunteers, 20-45 years of age, with a body mass index (BMI)
      within 18.5-30.0 kg/m2, inclusive, will be enrolled. (The body weight should be over 50 kg,
      inclusive, respectively)

      A single dose of 8 puffs (eq. to budesonide 1280 μg /formoterol fumarate dihydrate 36 μg) in
      each study period.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under Curve (AUC)
time frame: Pre-dose and at 0.03, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24 and 36 hours after dosing.
measure: Maximum plasma concentration (Cmax)
time frame: Pre-dose and at 0.03, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24 and 36 hours after dosing.
measure: Time to reach Maximum plasma concentration (Tmax)
time frame: Pre-dose and at 0.03, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24 and 36 hours after dosing.
measure: Blood pressure (BP)
time frame: Pre-dose and at 0.5, 16, 24 and 36 hours after dosing.
measure: Body temperature (BT)
time frame: Pre-dose and at 0.5, 16, 24 and 36 hours after dosing.
measure: Pulse rate (PR)
time frame: Pre-dose and at 0.5, 16, 24 and 36 hours after dosing.
arm group label: Reference 1 Symbicort Inhaler 160/4.5μg
arm group type: Active Comparator
description: Reference 1: Symbicort Inhaler (Budesonide/ Formoterol, 160/4.5μg), Single dose, 8 puffs
arm group label: SYN010 HFA Inhaler
arm group type: Experimental
description: SYN010 HFA (Budesonide/ Formoterol, 160/4.5μg), Single dose, 8 puffs
arm group label: Reference 2 Symbicort Inhaler 160/4.5μg
arm group type: Active Comparator
description: Reference 2: Symbicort Inhaler (Budesonide/ Formoterol, 160/4.5μg), Single dose, 8 puffs
intervention type: Drug
intervention name: Budesonide
description: Inhaled corticosteroid
arm group label: Reference 1 Symbicort Inhaler 160/4.5μg
arm group label: Reference 2 Symbicort Inhaler 160/4.5μg
arm group label: SYN010 HFA Inhaler
intervention type: Drug
intervention name: Formoterol
description: Long Acting Beta Agonist (LABA)
arm group label: Reference 1 Symbicort Inhaler 160/4.5μg
arm group label: Reference 2 Symbicort Inhaler 160/4.5μg
arm group label: SYN010 HFA Inhaler
criteria: 
gender: All
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wen-Kuei Chang, M.D.
role: Principal Investigator
affiliation: Clinical Pharmacology Unit of Mackay Memorial Hospital Tamshui Branch
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Budesonide
mesh term: Formoterol Fumarate
sharing ipd: Undecided