<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/NCT03822364</url>
  </required_header>
  <id_info>
    <org_study_id>AMDC-009-101</org_study_id>
    <nct_id>NCT03822364</nct_id>
  </id_info>
  <brief_title>Staccato Apomorphine Single and Multi Dose PK</brief_title>
  <official_title>A Randomized Study of the Safety, Tolerability, and Pharmacokinetics of AZ-009 (Staccato Apomorphine) in Healthy Volunteers and the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZ-009 in Subjects With Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alexza Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alexza Pharmaceuticals, Inc.</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>
      This study will be conducted in 3 parts. A) compare the pharmacokinetics (PK) of a single&#xD;
      dose of AZ-009 with that of a therapeutically-relevant dose of a commercially available&#xD;
      apomorphine injector in healthy volunteers; B) ascending doses of active drug in healthy&#xD;
      volunteers; and C) examine the tolerability, safety, and PK of AZ-009 in subjects with&#xD;
      established Parkinson's disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be conducted in 3 parts. Parts A and B will be conducted in healthy&#xD;
      volunteers and Part C will be conducted in subjects with established Parkinson's disease. The&#xD;
      primary objectives for each part are as follows.&#xD;
&#xD;
      Part A: To compare the pharmacokinetics of a single low dose of AZ-009 with that of a&#xD;
      therapeutically-relevant dose a commercially available apomorphine injector in healthy&#xD;
      volunteers.&#xD;
&#xD;
      Part B: To examine the tolerability and safety of AZ-009 of single ascending doses of active&#xD;
      drug in healthy volunteers while; and to characterize the pharmacokinetics of single&#xD;
      ascending doses of AZ-009 in healthy volunteers&#xD;
&#xD;
      Part C: To examine the tolerability, safety, and pharmacokinetics of AZ-009 in subjects with&#xD;
      established Parkinson's disease and to identify optimal doses to bring into multiple&#xD;
      ascending dose safety and efficacy studies; and to assess the usability of AZ-009 in subjects&#xD;
      with Parkinson's Disease&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 26, 2018</start_date>
  <completion_date type="Actual">March 26, 2019</completion_date>
  <primary_completion_date type="Actual">March 26, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>A 3 part study including: A) Single Dose Crossover in Healthy Volunteers, B) Single Ascending Dose with placebo control in Healthy Volunteers, and C) Single Ascending Dose with placebo control in Subjects with Established Parkinson's Disease</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A-Relative bioavailability of inhaled Staccato apomorphine dose compared to the subcutaneous administration</measure>
    <time_frame>24 hours</time_frame>
    <description>Relative bioavailability of inhaled Staccato apomorphine compared to active comparator injection based on the Geometric Least Squares Mean Ratio of AUCinf for all subjects completing the crossover part of the trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>B-Dose Proportionality by Power Analysis of AUCinf</measure>
    <time_frame>24 hours</time_frame>
    <description>Dose proportionality of inhaled Staccato apomorphine AUCinf across all doses administered in the single ascending dose portions of the study (Parts B and C) using a power model [regression of log(AUCinf) versus log(dose)]</description>
  </primary_outcome>
  <number_of_arms>14</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>A-1 (009-1 -&gt; active comparator)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A, Arm 1 (Inhaled apomorphine, Dose 1 followed by commercially available active comparator)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A-2 (active comparator -&gt; 009-1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A, Arm 2 (commercially available active comparator followed by Inhaled apomorphine, Dose 1)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B-1a (009-2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B, Arm 1 (Inhaled apomorphine, Dose 2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B-1p (009-0)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part B, Arm 1 (Inhaled placebo)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B-2a (009-3)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Part B, Arm 2 (Inhaled apomorphine, Dose 3)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B-2p (009-0)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part B, Arm 2 (Inhaled placebo)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B-3a (009-4)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B, Arm 3 (Inhaled apomorphine, Dose 4)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B-3p (009-0)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part B, Arm 3 (Inhaled placebo)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C-1a (009-3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part C, Arm 1 (Inhaled apomorphine, Dose 3)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C-1p (009-0)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part C, Arm 1 (Inhaled placebo)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C-2a (009-4)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part C, Arm 2 (Inhaled apomorphine, Dose 4)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C-2p (009-0)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part C, Arm 2 (Inhaled placebo)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C-3a (009-5)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part C, Arm 3 (Inhaled apomorphine, Dose 5)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C-3p (009-0)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part C, Arm 3 (Inhaled placebo)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>009-1</intervention_name>
    <description>Inhaled apomorphine via Staccato aerosol, Dose 1</description>
    <arm_group_label>A-1 (009-1 -&gt; active comparator)</arm_group_label>
    <arm_group_label>A-2 (active comparator -&gt; 009-1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>active comparator</intervention_name>
    <description>commercially available apomorphine injector</description>
    <arm_group_label>A-1 (009-1 -&gt; active comparator)</arm_group_label>
    <arm_group_label>A-2 (active comparator -&gt; 009-1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>009-0</intervention_name>
    <description>Inhaled placebo via Staccato device</description>
    <arm_group_label>B-1p (009-0)</arm_group_label>
    <arm_group_label>B-2p (009-0)</arm_group_label>
    <arm_group_label>B-3p (009-0)</arm_group_label>
    <arm_group_label>C-1p (009-0)</arm_group_label>
    <arm_group_label>C-2p (009-0)</arm_group_label>
    <arm_group_label>C-3p (009-0)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>009-2</intervention_name>
    <description>Inhaled apomorphine via Staccato aerosol, Dose 2</description>
    <arm_group_label>B-1a (009-2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>009-3</intervention_name>
    <description>Inhaled apomorphine via Staccato aerosol, Dose 3</description>
    <arm_group_label>B-2a (009-3)</arm_group_label>
    <arm_group_label>C-1a (009-3)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>009-4</intervention_name>
    <description>Inhaled apomorphine via Staccato aerosol, Dose 4</description>
    <arm_group_label>B-3a (009-4)</arm_group_label>
    <arm_group_label>C-2a (009-4)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>009-5</intervention_name>
    <description>Inhaled apomorphine via Staccato aerosol, Dose 5</description>
    <arm_group_label>C-3a (009-5)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adult males and females between 18 and 60 years of age, inclusive at the time&#xD;
             of signing the informed consent document.&#xD;
&#xD;
          -  Body weight ≥ 50 kg and BMI within the range of 18 to 32 kg/m2.&#xD;
&#xD;
          -  Willing and able to be confined at the clinical research center for the study period&#xD;
             and adhere to overall study visit schedule, procedures and other protocol&#xD;
             requirements.&#xD;
&#xD;
          -  Understand and voluntarily sign an informed consent document prior to any study&#xD;
             related assessments/procedures being conducted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any significant medical condition, psychiatric illness or history of depression that&#xD;
             could, in the investigator's opinion, compromise the subject's safety or interfere&#xD;
             with the completion of this protocol.&#xD;
&#xD;
          -  History of clinically significant central nervous system, cardiac, pulmonary,&#xD;
             metabolic, renal, hepatic, or gastrointestinal conditions including gastric bypass or&#xD;
             other weight loss surgical procedure; or history of such conditions that, in the&#xD;
             opinion of the investigator, may place the subject at an unacceptable risk as a&#xD;
             participant in this trial.&#xD;
&#xD;
          -  Use of non-prescription medications within 5 days prior to the first dose of study&#xD;
             drug.&#xD;
&#xD;
          -  Use of medication that is inhibitor or inducer of CYP450-3A4/5 within 3 days of&#xD;
             dosing.&#xD;
&#xD;
          -  Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice,&#xD;
             Seville oranges, within 3 days prior to administration of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Geert J Groeneveld, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center for Human Drug Research (The Netherlands)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Human Drug Research</name>
      <address>
        <city>Leiden</city>
        <zip>2333 CL</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>August 28, 2019</last_update_submitted>
  <last_update_submitted_qc>August 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>apomorphine</keyword>
  <keyword>aerosol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_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/NCT03822364
org study id: AMDC-009-101
nct id: NCT03822364
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will be conducted in 3 parts. A) compare the pharmacokinetics (PK) of a single
      dose of AZ-009 with that of a therapeutically-relevant dose of a commercially available
      apomorphine injector in healthy volunteers; B) ascending doses of active drug in healthy
      volunteers; and C) examine the tolerability, safety, and PK of AZ-009 in subjects with
      established Parkinson's disease.
This study will be conducted in 3 parts. Parts A and B will be conducted in healthy
      volunteers and Part C will be conducted in subjects with established Parkinson's disease. The
      primary objectives for each part are as follows.

      Part A: To compare the pharmacokinetics of a single low dose of AZ-009 with that of a
      therapeutically-relevant dose a commercially available apomorphine injector in healthy
      volunteers.

      Part B: To examine the tolerability and safety of AZ-009 of single ascending doses of active
      drug in healthy volunteers while; and to characterize the pharmacokinetics of single
      ascending doses of AZ-009 in healthy volunteers

      Part C: To examine the tolerability, safety, and pharmacokinetics of AZ-009 in subjects with
      established Parkinson's disease and to identify optimal doses to bring into multiple
      ascending dose safety and efficacy studies; and to assess the usability of AZ-009 in subjects
      with Parkinson's Disease
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A 3 part study including: A) Single Dose Crossover in Healthy Volunteers, B) Single Ascending Dose with placebo control in Healthy Volunteers, and C) Single Ascending Dose with placebo control in Subjects with Established Parkinson's Disease
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: A-Relative bioavailability of inhaled Staccato apomorphine dose compared to the subcutaneous administration
time frame: 24 hours
description: Relative bioavailability of inhaled Staccato apomorphine compared to active comparator injection based on the Geometric Least Squares Mean Ratio of AUCinf for all subjects completing the crossover part of the trial
measure: B-Dose Proportionality by Power Analysis of AUCinf
time frame: 24 hours
description: Dose proportionality of inhaled Staccato apomorphine AUCinf across all doses administered in the single ascending dose portions of the study (Parts B and C) using a power model [regression of log(AUCinf) versus log(dose)]
arm group label: A-1 (009-1 -> active comparator)
arm group type: Experimental
description: Part A, Arm 1 (Inhaled apomorphine, Dose 1 followed by commercially available active comparator)
arm group label: A-2 (active comparator -> 009-1)
arm group type: Experimental
description: Part A, Arm 2 (commercially available active comparator followed by Inhaled apomorphine, Dose 1)
arm group label: B-1a (009-2)
arm group type: Experimental
description: Part B, Arm 1 (Inhaled apomorphine, Dose 2)
arm group label: B-1p (009-0)
arm group type: Placebo Comparator
description: Part B, Arm 1 (Inhaled placebo)
arm group label: B-2a (009-3)
arm group type: Active Comparator
description: Part B, Arm 2 (Inhaled apomorphine, Dose 3)
arm group label: B-2p (009-0)
arm group type: Placebo Comparator
description: Part B, Arm 2 (Inhaled placebo)
arm group label: B-3a (009-4)
arm group type: Experimental
description: Part B, Arm 3 (Inhaled apomorphine, Dose 4)
arm group label: B-3p (009-0)
arm group type: Placebo Comparator
description: Part B, Arm 3 (Inhaled placebo)
arm group label: C-1a (009-3)
arm group type: Experimental
description: Part C, Arm 1 (Inhaled apomorphine, Dose 3)
arm group label: C-1p (009-0)
arm group type: Placebo Comparator
description: Part C, Arm 1 (Inhaled placebo)
arm group label: C-2a (009-4)
arm group type: Experimental
description: Part C, Arm 2 (Inhaled apomorphine, Dose 4)
arm group label: C-2p (009-0)
arm group type: Placebo Comparator
description: Part C, Arm 2 (Inhaled placebo)
arm group label: C-3a (009-5)
arm group type: Experimental
description: Part C, Arm 3 (Inhaled apomorphine, Dose 5)
arm group label: C-3p (009-0)
arm group type: Placebo Comparator
description: Part C, Arm 3 (Inhaled placebo)
intervention type: Drug
intervention name: 009-1
description: Inhaled apomorphine via Staccato aerosol, Dose 1
arm group label: A-1 (009-1 -> active comparator)
arm group label: A-2 (active comparator -> 009-1)
intervention type: Drug
intervention name: active comparator
description: commercially available apomorphine injector
arm group label: A-1 (009-1 -> active comparator)
arm group label: A-2 (active comparator -> 009-1)
intervention type: Drug
intervention name: 009-0
description: Inhaled placebo via Staccato device
arm group label: B-1p (009-0)
arm group label: B-2p (009-0)
arm group label: B-3p (009-0)
arm group label: C-1p (009-0)
arm group label: C-2p (009-0)
arm group label: C-3p (009-0)
intervention type: Drug
intervention name: 009-2
description: Inhaled apomorphine via Staccato aerosol, Dose 2
arm group label: B-1a (009-2)
intervention type: Drug
intervention name: 009-3
description: Inhaled apomorphine via Staccato aerosol, Dose 3
arm group label: B-2a (009-3)
arm group label: C-1a (009-3)
intervention type: Drug
intervention name: 009-4
description: Inhaled apomorphine via Staccato aerosol, Dose 4
arm group label: B-3a (009-4)
arm group label: C-2a (009-4)
intervention type: Drug
intervention name: 009-5
description: Inhaled apomorphine via Staccato aerosol, Dose 5
arm group label: C-3a (009-5)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Geert J Groeneveld, MD, PhD
role: Principal Investigator
affiliation: Center for Human Drug Research (The Netherlands)
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Parkinson Disease
sharing ipd: Undecided