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/NCT06013150</url>
    </required_header>
    <id_info>
      <org_study_id>DMC-CL-002</org_study_id>
      <nct_id>NCT06013150</nct_id>
    </id_info>
    <brief_title>Study of Inhaled DMC-IH1 and Intramuscular (EpiPen®) Epinephrine in Healthy Male and Female Participants.</brief_title>
    <official_title>A Phase 1, 2-Part Study in Healthy Male and Female Participants; Part 1 - A Randomised, Double-Blind, Placebo-Controlled, Single Ascending Dose-Escalation Study of Inhaled DMC-IH1; Part 2 - An Open-Label, 3-Arm Study Assessing the Carryover Effects of Inhaled (DMC-IH1) and Intramuscular (EpiPen®) Epinephrine</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>De Motu Cordis</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Novotech (Australia) Pty Limited</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>De Motu Cordis</source>
    <oversight_info>
      <has_dmc>Yes</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, randomised, double blind placebo controlled 2-part study to assess the&#xD;
        safety, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled DMC-IH1 (epinephrine) and&#xD;
        relative bioavailability and carryover effects of Inhaled (DMC-IH1) and Intramuscular(IM)&#xD;
        (EpiPen®) Epinephrine in healthy male and female participants.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        DMC-IH1 (Investigational product) inhaler is a proprietary single-use capsule based dry&#xD;
        powder inhaler designed for oral pulmonary drug delivery in emergency scenarios.&#xD;
  &#xD;
        This study is in two parts- Part 1 will enrol 24 participants into 3 cohorts receiving a&#xD;
        single ascending dose; Part 2 will enrol 39 participants into 3 arms to receive either&#xD;
        DMC-IH1 through the inhaler device or epinephrine IM.&#xD;
  &#xD;
        Each participant will receive 3 doses of epinephrine either inhaled (DMC-IH1) or IM at&#xD;
        differing intervals to assess carryover effect.&#xD;
  &#xD;
        Both Parts 1 and 2 of the study will comprise 3 periods: Screening, Treatment Period and&#xD;
        Follow-up .&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 23, 2023</start_date>
    <completion_date type="Anticipated">February 12, 2024</completion_date>
    <primary_completion_date type="Anticipated">January 18, 2024</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>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with adverse events (AEs)</measure>
      <time_frame>Upto 7 days for Part 1; Upto 16 days for Part 2</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with clinical laboratory abnormalities</measure>
      <time_frame>Upto 7 days for Part 1; Upto 16 days for Part 2</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with changes in the 12-lead electrocardiogram (ECG)</measure>
      <time_frame>Upto 7 days for Part 1; Upto 16 days for Part 2</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>PK Parameters: Assess timepoints of carryover effect of repeated dose of inhaled epinephrine</measure>
      <time_frame>Upto 7days post effect in Part 2 of the study</time_frame>
      <description>Part 1: Pre-dose and multiple timepoints post dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on Days 1, 4, and 9 (Arm 1) and on Days 1, 2, and 9 (Arms 2 and 3).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>PK Parameters: Time for maximum concentration (Tmax)</measure>
      <time_frame>Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 &amp; 3)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK Parameters: Maximum concentration (Cmax)</measure>
      <time_frame>Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 &amp; 3)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK Parameters: Area under Curve (AUC)</measure>
      <time_frame>Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 &amp; 3)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PD parameters: Maximum effect on heart rate and blood pressure (Emax)</measure>
      <time_frame>Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PD parameters: Time to maximum effect (TEmax)</measure>
      <time_frame>Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">63</enrollment>
    <condition>Anaphylactic Reaction</condition>
    <arm_group>
      <arm_group_label>Epinephrine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dosage Level:&#xD;
  Part 1 of the study: Participants across cohort 1 to 3 will receive a single dose of either 1mg or 1.3mg or 1.5mg respectively of epinephrine or placebo via DMC-IHI device.&#xD;
  Part 2 of the study: This is an open label where participants will receive multiple doses of inhaled epinephrine via DMC-IHI across 5 cohorts the highest tolerated dose based on safety, PK, PD data from Part 1 of the study on.&#xD;
  Dosage form: Single-use capsule based dry powder inhaler or EpiPen® IM&#xD;
  Route of administraion: Inhalation (Part 1 and Part 2) and Intramuscular (Part 2)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Drug: Placebo&#xD;
  Participants will receive matching placebo across the Part 1 of the study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Epinephrine</intervention_name>
      <description>Participants in Part 1 of the study will receive single dose either 1mg, 1.3mg or 1.5mg of an inhaled single dose of Epinephrine or placebo delivered via DMC-IHI device.&#xD;
  Participants in the Part 2 of the study will receive multiple doses of the Epinephrine based on MTD of Part 1 of the study.</description>
      <arm_group_label>Epinephrine</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Participant in Part 1 of the study will receive matching doses of placebo</description>
      <arm_group_label>Epinephrine</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Is willing to sign an ICF on a voluntary basis and to voluntarily participate in the&#xD;
               study, after being able to read the ICF and understand the information contained&#xD;
               within, prior to any Screening procedure being undertaken.&#xD;
  &#xD;
            2. Male or female and ≥18 to ≤45 years of age at time of signing the ICF.&#xD;
  &#xD;
            3. Has a BMI of ≥18.00 to ≤30.00 kg/m2, with a minimum body weight of 45.0 kg and a&#xD;
               maximum body weight of 120 kg.&#xD;
  &#xD;
            4. Is in good health based on the results of medical and surgical history, physical&#xD;
               examination, vital sign measurements, and clinical laboratory evaluations, as assessed&#xD;
               by the Investigator (or designee).&#xD;
  &#xD;
            5. Has a resting heart rate of ≥45 and ≤90 beats per minute; systolic blood pressure of&#xD;
               ≥90 but ≤130 mmHg and diastolic blood pressure of ≥50 but ≤90 mmHg at Screening (Visit&#xD;
               1) and prior to randomisation on Day -1 (Visit 2).&#xD;
  &#xD;
            6. Has normal lung function assessed using spirometry and defined by forced vital&#xD;
               capacity (FVC) ≥ lower limit of normal (LLN), forced expiratory volume in 1 second/FVC&#xD;
               ≥LLN, and peak inspiratory flow rate ≥ LLN at Screening (Visit 1).&#xD;
  &#xD;
            7. Has no history of anaphylaxis or severe allergy requiring the use of epinephrine.&#xD;
  &#xD;
            8. Is a non-smoker/non-vaping; or social smoker who currently only uses ≤5 cigarettes per&#xD;
               month and has used nicotine on ≤5 occasions within 30 days prior to Screening, a&#xD;
               negative cotinine test at Visit 2/Day -1, and ability and willingness to refrain from&#xD;
               smoking 7 days prior to the first epinephrine dose through the EOS [Part 1: Visit 3;&#xD;
               Part 2: Visit 6]).&#xD;
  &#xD;
            9. Has adequate venous access.&#xD;
  &#xD;
           10. Is able to demonstrate correct use of the device using a practice device and follow&#xD;
               directions for use.&#xD;
  &#xD;
           11. Able to follow contraceptive measures as per Protocol.&#xD;
  &#xD;
           12. Ability and willingness to refrain from undertaking any strenuous exercise (including&#xD;
               weightlifting) 48 hours prior to each clinic visit.&#xD;
  &#xD;
          14. Ability and willingness to refrain from alcohol and/or drug use from Screening (or at&#xD;
          least 1 week prior to dosing) (testing at Day -1 to ensure compliance) until EOS (Part&#xD;
          1:until Visit 3/EOS; Part 2: until Visit 6/EOS).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Participant who is pregnant or lactating at Screening or planning to become pregnant&#xD;
               (self or partner) at any time from screening to the end of study visit (Part 1:&#xD;
               through Visit 3/EOS; Part 2: through Visit 6/EOS).&#xD;
  &#xD;
            2. Participant has a history of significant hypersensitivity or intolerance to lactose&#xD;
               and/or epinephrine.&#xD;
  &#xD;
            3. Participant has a history or clinical manifestation of any metabolic, allergic,&#xD;
               dermatological, hepatic, renal, haematological, pulmonary, cardiovascular (including&#xD;
               severe pulmonary haemorrhage), gastrointestinal, neurological (including history of&#xD;
               migraine requiring specific treatment), respiratory, endocrine, or psychiatric&#xD;
               disorder, as determined by the Investigator (or designee) except for fully resolved&#xD;
               childhood asthma.&#xD;
  &#xD;
            4. Participant has a positive urine drug screen at Screening and at Baseline (Visit 2/Day&#xD;
               -1).&#xD;
  &#xD;
            5. Participant has a positive urine cotinine test at Baseline (Visit 2/Day -1).&#xD;
  &#xD;
            6. Participant took part in a clinical study involving administration of an&#xD;
               investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior&#xD;
               to Baseline (Visit 2/Day -1).&#xD;
  &#xD;
            7. Participant used or intends to use any prescription or non-prescription&#xD;
               medications/products within 14 days prior to randomization (Day -1) through EOS (Part&#xD;
               1: Visit 3/EOS; Part 2: Visit 6/EOS), with the exception of paracetamol/acetaminophen&#xD;
               at the discretion of the Investigator, and contraceptives.&#xD;
  &#xD;
            8. Participant has a history of alcoholism or substance or drug abuse-related disorders&#xD;
               deemed significant by the Investigator (or designee) (ie, &gt;14 drinks/week for women or&#xD;
               &gt;21 drinks/week for men [1 drink=150 mL of wine or 360 mL of beer or 45 mL of hard&#xD;
               liquor]) within the last 3 months prior to Screening (Visit 1) and randomization (Day&#xD;
               -1/Visit 2).&#xD;
  &#xD;
            9. Participant has a positive alcohol breath test at Screening and prior to randomization&#xD;
               (Day -1/Visit 2).&#xD;
  &#xD;
           10. Female participant has a positive serum pregnancy test at Screening and a positive&#xD;
               urine pregnancy test prior to randomization (Day -1/Visit 2).&#xD;
  &#xD;
           11. Participant has a positive test for human immunodeficiency virus (HIV), hepatitis B&#xD;
               surface antigen, or hepatitis C virus antibody (anti-HCV) with HCV RNA detected at&#xD;
               Screening and hepatitis B core antibody at Screening.&#xD;
  &#xD;
           12. Participant has presence of any physical or psychological medical condition that, in&#xD;
               the opinion of the Investigator, would make it unlikely that the participant will&#xD;
               comply with the protocol or complete the study per protocol.&#xD;
  &#xD;
           13. Participant has received any of the following vaccinations:&#xD;
  &#xD;
                 1. Live vaccine(s) within 1 month prior to Screening or plans to receive such&#xD;
                    vaccines during the study.&#xD;
  &#xD;
                 2. Killed vaccine 1 week prior to randomization (Day -1/Visit 2).&#xD;
  &#xD;
                 3. COVID-19 vaccine Day -7 through Visit 3 for Part 1 and through Visit 6 for Part 2&#xD;
                    (EOS).&#xD;
  &#xD;
           14. Participant had surgery of the nose/paranasal sinuses/mouth/throat within 8 weeks or&#xD;
               thoracic surgery within 24 weeks prior to Screening or randomization (Day -1/Visit 2).&#xD;
  &#xD;
           15. Participant has any history of clinically relevant respiratory (especially with&#xD;
               reduction of respiratory capacity) or history of clinically significant cardiovascular&#xD;
               abnormality (eg, including hypertension, ischemic heart disease, previous myocardial&#xD;
               infarct, heart failure or conduction abnormalities (SVT, AF, interventricular&#xD;
               conduction blocks, etc.) or any other abnormality that in the opinion of the&#xD;
               Investigator may pose a safety risk to a participant), or any other abnormality that&#xD;
               in the opinion of the Investigator may pose a safety risk to a participant in this&#xD;
               study may confound the clinical performance or safety assessment, or may interfere&#xD;
               with study participation.&#xD;
  &#xD;
           16. Participant has any of the following ECG criteria:&#xD;
  &#xD;
                 1. PR interval &gt;220 ms or &lt;120 ms&#xD;
  &#xD;
                 2. QRS interval &gt;120 ms&#xD;
  &#xD;
                 3. QTcF interval &gt;450 ms (males) or &gt;470 ms (females)&#xD;
  &#xD;
                 4. A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of&#xD;
                    a QTc interval &gt;450 ms)&#xD;
  &#xD;
                 5. ST segment elevation or depression considered to be clinically significant by the&#xD;
                    PI or designee&#xD;
  &#xD;
                 6. T-wave or U-wave abnormalities considered to be clinically significant by the PI&#xD;
                    or designee -&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Peter O'Neil</last_name>
      <role>Study Director</role>
      <affiliation>peter.oneill@demotucordis.co</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>John Fredatovich</last_name>
      <phone>+61 07 3520 0350</phone>
      <email>john.fredatovich@demotucordis.co</email>
    </overall_contact>
    <location>
      <facility>
        <name>CMAX Clinical Research</name>
        <address>
          <city>Adelaide</city>
          <state>South Australia</state>
          <zip>5000</zip>
          <country>Australia</country>
        </address>
      </facility>
      <contact>
        <last_name>CMAX C Research</last_name>
      </contact>
      <contact_backup>
        <last_name>Angela Rowland, Dr</last_name>
        <email>Teamrowland08@yahoo.com.au</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Australia</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anaphylaxis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epinephrine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06013150
  org study id: DMC-CL-002
  nct id: NCT06013150
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a phase 1, randomised, double blind placebo controlled 2-part study to assess the
        safety, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled DMC-IH1 (epinephrine) and
        relative bioavailability and carryover effects of Inhaled (DMC-IH1) and Intramuscular(IM)
        (EpiPen®) Epinephrine in healthy male and female participants.
  DMC-IH1 (Investigational product) inhaler is a proprietary single-use capsule based dry
        powder inhaler designed for oral pulmonary drug delivery in emergency scenarios.
  
        This study is in two parts- Part 1 will enrol 24 participants into 3 cohorts receiving a
        single ascending dose; Part 2 will enrol 39 participants into 3 arms to receive either
        DMC-IH1 through the inhaler device or epinephrine IM.
  
        Each participant will receive 3 doses of epinephrine either inhaled (DMC-IH1) or IM at
        differing intervals to assess carryover effect.
  
        Both Parts 1 and 2 of the study will comprise 3 periods: Screening, Treatment Period and
        Follow-up .
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Number of participants with adverse events (AEs)
  time frame: Upto 7 days for Part 1; Upto 16 days for Part 2
  measure: Number of participants with clinical laboratory abnormalities
  time frame: Upto 7 days for Part 1; Upto 16 days for Part 2
  measure: Number of participants with changes in the 12-lead electrocardiogram (ECG)
  time frame: Upto 7 days for Part 1; Upto 16 days for Part 2
  measure: PK Parameters: Assess timepoints of carryover effect of repeated dose of inhaled epinephrine
  time frame: Upto 7days post effect in Part 2 of the study
  description: Part 1: Pre-dose and multiple timepoints post dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on Days 1, 4, and 9 (Arm 1) and on Days 1, 2, and 9 (Arms 2 and 3).
  measure: PK Parameters: Time for maximum concentration (Tmax)
  time frame: Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 & 3)
  measure: PK Parameters: Maximum concentration (Cmax)
  time frame: Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 & 3)
  measure: PK Parameters: Area under Curve (AUC)
  time frame: Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 & 3)
  measure: PD parameters: Maximum effect on heart rate and blood pressure (Emax)
  time frame: Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose
  measure: PD parameters: Time to maximum effect (TEmax)
  time frame: Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose
  arm group label: Epinephrine
  arm group type: Experimental
  description: Dosage Level:
  Part 1 of the study: Participants across cohort 1 to 3 will receive a single dose of either 1mg or 1.3mg or 1.5mg respectively of epinephrine or placebo via DMC-IHI device.
  Part 2 of the study: This is an open label where participants will receive multiple doses of inhaled epinephrine via DMC-IHI across 5 cohorts the highest tolerated dose based on safety, PK, PD data from Part 1 of the study on.
  Dosage form: Single-use capsule based dry powder inhaler or EpiPen® IM
  Route of administraion: Inhalation (Part 1 and Part 2) and Intramuscular (Part 2)
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Drug: Placebo
  Participants will receive matching placebo across the Part 1 of the study.
  intervention type: Drug
  intervention name: Epinephrine
  description: Participants in Part 1 of the study will receive single dose either 1mg, 1.3mg or 1.5mg of an inhaled single dose of Epinephrine or placebo delivered via DMC-IHI device.
  Participants in the Part 2 of the study will receive multiple doses of the Epinephrine based on MTD of Part 1 of the study.
  arm group label: Epinephrine
  arm group label: Placebo
  intervention type: Drug
  intervention name: Placebo
  description: Participant in Part 1 of the study will receive matching doses of placebo
  arm group label: Epinephrine
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Peter O'Neil
  role: Study Director
  affiliation: peter.oneill@demotucordis.co
  last name: John Fredatovich
  phone: +61 07 3520 0350
  email: john.fredatovich@demotucordis.co
  facility: 
  contact: 
  contact backup: 
  country: Australia
  responsible party type: Sponsor
  mesh term: Anaphylaxis
  mesh term: Epinephrine
  sharing ipd: No