<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/NCT02184767</url>
  </required_header>
  <id_info>
    <org_study_id>TV571-CNS-10018</org_study_id>
    <nct_id>NCT02184767</nct_id>
  </id_info>
  <brief_title>Study to Assess the Safety and Pharmacokinetics of ADASUVE® at Doses of 2.5, 5, or 10 mg in Children and Adolescents (10 Through 17 Years of Age) With Any Condition Warranting Chronic Use of an Antipsychotic Medication</brief_title>
  <official_title>A Nonrandomized, Open-Label, Multicenter, Phase 1 Study to Assess the Safety and Pharmacokinetics of ADASUVE® (STACCATO® Loxapine for Inhalation) at Doses of 2.5, 5, or 10 mg in Children and Adolescents (10 Through 17 Years of Age) With Any Condition Warranting Chronic Use of an Antipsychotic Medication</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Teva Branded Pharmaceutical Products R&amp;D, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Teva Branded Pharmaceutical Products R&amp;D, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to assess the pharmacokinetics of loxapine and will be using plasma&#xD;
      concentration data obtained over 48 hours after administration of the study drug&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t)</measure>
    <time_frame>48 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ratio of AUC0-t to AUC0-inf (AUC0-t/AUC0-inf)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>maximum observed plasma drug concentration (Cmax)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to maximum observed concentration (tmax)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>apparent terminal elimination rate constant (Kel)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>elimination half-life (t½)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>apparent clearance (CL/F)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>volume of distribution (V/F)</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The palatability of ADASUVE will be performed using a visual analog scale (VAS)</measure>
    <time_frame>2 1/2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of participants with adverse events</measure>
    <time_frame>3 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>BiPolar</condition>
  <arm_group>
    <arm_group_label>ADASUVE®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral inhalation using a single-use, hand-held, inhaler; dosage determined by the investigator according the participants weight</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADASUVE®</intervention_name>
    <description>ADASUVE® 2.5, 5, or 10 mg</description>
    <arm_group_label>ADASUVE®</arm_group_label>
    <other_name>STACCATO® Loxapine for Inhalation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion&#xD;
&#xD;
          1. Written informed consent is obtained from each patient's parent or legal guardian and&#xD;
             written assent is obtained from each patient.&#xD;
&#xD;
          2. The patient is a boy or girl 10 through 17 years of age.&#xD;
&#xD;
          3. The patient is within the 2.5 to 97.5 percentile for body mass index (BMI) on the&#xD;
             basis of age and sex and is within the following weight range, as appropriate:&#xD;
&#xD;
               -  boys: more than 27 kg and 127 kg or less&#xD;
&#xD;
               -  girls: more than 27 kg and 111 kg or less&#xD;
&#xD;
          4. The patient has a documented history of schizophrenia, bipolar disorder, autism, or&#xD;
             any condition for which the use of antipsychotic medication (eg, risperidone,&#xD;
             olanzapine, aripirazole, haloperidol, etc.) is warranted and/or administered. Note:&#xD;
             Patients currently receiving treatment for any condition must be on a stable regimen&#xD;
             (dose and frequency) for a minimum of 28 days before administration of ADASUVE.&#xD;
&#xD;
          5. The patient is in good general health as determined by a complete medical history&#xD;
             (including psychiatric and respiratory), clinical laboratory tests (include&#xD;
             hematology, serum chemistry, and urinalysis), physical examination, body weight,&#xD;
             12-lead ECG, spirometry, vital signs measurements (blood pressure [systolic and&#xD;
             diastolic], heart rate, body temperature, and respiratory rate), pulse oximetry, chest&#xD;
             auscultation, neurologic examination, suicidality assessment, and concomitant&#xD;
             medication usage inquiry.&#xD;
&#xD;
          6. Female patients who are postmenarche or sexually active must have a negative pregnancy&#xD;
             test result, must have exclusively same sex partners or be using an acceptable method&#xD;
             of contraception, and must agree to continued use of this method for the duration of&#xD;
             the study and for 30 days after discontinuation of ADASUVE. Acceptable methods of&#xD;
             contraception include abstinence or an intrauterine device (known to have a failure&#xD;
             rate of less than 1% per year).&#xD;
&#xD;
          7. The patient has negative alcohol test and urine drug screen (UDS) results. A positive&#xD;
             UDS result with appropriate medical explanation (eg, prescribed amphetamines) may be&#xD;
             permitted after consultation with the medical monitor. Note: The UDS will also detect&#xD;
             the presence of tetrahydrocannabinol (THC). A positive result for THC may be permitted&#xD;
             after discussion with the sponsor if the result is low and is consistent (eg, positive&#xD;
             at all predose assessments). If a patient tests negative for THC at screening, the&#xD;
             result must remain negative at check-in for the patient to be eligible for study&#xD;
             participation.&#xD;
&#xD;
          8. The patient and parent/legal guardian must be willing and able to comply with study&#xD;
             restrictions and to remain at the investigational center for the required duration at&#xD;
             each visit.&#xD;
&#xD;
        Exclusion&#xD;
&#xD;
          1. The patient has any clinically significant uncontrolled medical condition (treated or&#xD;
             untreated) other than the conditions specified in inclusion criterion d.&#xD;
&#xD;
          2. The patient has a current diagnosis or history of asthma, chronic obstructive&#xD;
             pulmonary disease (COPD), bronchiolitis, chronic bronchitis, emphysema, or other lung&#xD;
             disease associated with bronchospasm.&#xD;
&#xD;
          3. The patient has acute respiratory signs or symptoms (eg, wheezing)&#xD;
&#xD;
          4. The patient currently has or has a known history of the following:&#xD;
&#xD;
               -  cardiovascular disease (including, but not limited to, myocardial infarction or&#xD;
                  ischemic heart disease, heart failure, or conduction abnormalities)&#xD;
&#xD;
               -  cerebrovascular disease&#xD;
&#xD;
               -  conditions that predispose him or her to hypotension (including, but not limited&#xD;
                  to, dehydration, hypovolemia, or treatment with antihypertensive medications or&#xD;
                  other drugs that affect blood pressure or reduce heart rate)&#xD;
&#xD;
               -  seizure disorder except a history of infantile febrile seizures&#xD;
&#xD;
          5. The patient is pregnant or lactating.&#xD;
&#xD;
          6. The patient is febrile.&#xD;
&#xD;
          7. The patient has any other disease or condition that, in the investigator's or medical&#xD;
             monitor's opinion, would present undue risk to the patient, or may confound the&#xD;
             interpretation of study results.&#xD;
&#xD;
          8. The patient has taken any of the following drugs, substances, or foods:&#xD;
&#xD;
               -  any investigational drug within 30 days or 5 half-lives (whichever is longer)&#xD;
                  before administration of ADASUVE or, in the case of a new chemical entity, 3&#xD;
                  months or 5 half-lives (whichever is longer) before administration of ADASUVE&#xD;
&#xD;
               -  current use of medications to treat airway disease such as asthma or COPD&#xD;
&#xD;
               -  loxapine or amoxapine within the last 30 days&#xD;
&#xD;
               -  more than 21 units of alcohol per week within the past 2 years or a history of&#xD;
                  alcohol, narcotic, or any other substance abuse or dependence as defined by the&#xD;
                  Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text&#xD;
                  Revision (DSM-IV-TR, American Psychiatric Association 2000). Note: A unit of&#xD;
                  alcohol is equal to 1 ounce of hard liquor, 5 ounces of wine, or 8 ounces of&#xD;
                  beer.&#xD;
&#xD;
               -  clinically significant excessive consumption of coffee, tea, and/or other&#xD;
                  caffeine-containing beverage or food (ie, 600 mg of caffeine or more per day, or&#xD;
                  12-ounce caffeine-containing sodas, 30 ounces of chocolate, or 5 or more cups of&#xD;
                  coffee per day), or a combination of any of these beverages or foods within 2&#xD;
                  weeks before the dose of ADASUVE&#xD;
&#xD;
               -  nicotine-containing products (including but not limited to cigarettes, cigars,&#xD;
                  and chewing or dipping tobacco) within 12 months before administration of ADASUVE&#xD;
                  or use of topical or oral nicotine preparations for smoking cessation within the&#xD;
                  past 3 months before administration of ADASUVE&#xD;
&#xD;
          9. The patient has a known sensitivity or idiosyncratic reaction to loxapine or&#xD;
             amoxapine, any compound present in the study formulation, any metabolites, or any&#xD;
             other related compounds.&#xD;
&#xD;
         10. The patient has a history of any clinically significant cutaneous drug reaction, or a&#xD;
             history of clinically significant hypersensitivity reaction, including multiple&#xD;
             allergies or drug reactions.&#xD;
&#xD;
         11. The patient has a known history of contraindications to anticholinergics (eg, bowel&#xD;
             obstructions, urinary retention, or acute glaucoma).&#xD;
&#xD;
         12. The patient has any procedure or disorder that may interfere with drug absorption,&#xD;
             distribution, metabolism, or excretion (including gastrointestinal surgery; a history&#xD;
             of appendectomy is allowed).&#xD;
&#xD;
         13. The patient has received or donated blood or blood products (eg, plasma or platelets)&#xD;
             in the 3 months before administration of ADASUVE or has made more than 2 blood (≥ 450&#xD;
             mL) or blood product donations within the 12 months before administration of ADASUVE,&#xD;
             or has plans to donate during the study or within 3 months after completion of the&#xD;
             study.&#xD;
&#xD;
         14. The patient has 1 or more clinical laboratory test values outside the range specified&#xD;
             below, or any other clinically significant laboratory abnormality, as determined by&#xD;
             the investigator or medical monitor:&#xD;
&#xD;
               -  hemoglobin value of less than 11.0 g/dL&#xD;
&#xD;
               -  more than twice the upper limit of the normal range (ULN)&#xD;
&#xD;
               -  total bilirubin value of more than the ULN&#xD;
&#xD;
         15. With the exception of the conditions specified in inclusion criterion d, the patient&#xD;
             has had, within 4 weeks before administration of ADASUVE, a clinically significant&#xD;
             illness or, within 1 week before administration of ADASUVE, has had any acute illness,&#xD;
             or at screening or on the day before administration of ADASUVE, has symptoms of any&#xD;
             clinically significant or acute illness.&#xD;
&#xD;
         16. The patient has a positive test result for hepatitis B surface antigen (HBsAg) or&#xD;
             antibodies to hepatitis C virus, or has a known positive human immunodeficiency virus&#xD;
             (HIV) history.&#xD;
&#xD;
         17. The patient is unable to tolerate direct venipuncture.&#xD;
&#xD;
         18. The patient has blood pressure outside the range of 90 to 140 mm Hg (systolic) or 50&#xD;
             to 90 mm Hg (diastolic). Note: Only 2 rechecks are permissible for study eligibility&#xD;
             purposes.&#xD;
&#xD;
         19. The patient has, after resting for 5 minutes, an oxygen saturation at less than 95%.&#xD;
             Note: Only 2 rechecks are permissible for study eligibility purposes.&#xD;
&#xD;
         20. The patient has evidence of a clinically significant ECG abnormality.&#xD;
&#xD;
         21. The patient has a forced expiratory volume in 1 second (FEV1) of less than 80% of&#xD;
             predicted value on spirometry.&#xD;
&#xD;
         22. The patient is unlikely to comply with the study protocol, or is unsuitable for any&#xD;
             other reasons, as judged by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sponsor Medical Expert, MD</last_name>
    <role>Study Director</role>
    <affiliation>Teva Branded Pharmaceutical Products R&amp;D, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Teva Investigational Site 12468</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12469</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>November 5, 2021</last_update_submitted>
  <last_update_submitted_qc>November 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 12, 2021</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>Loxapine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02184767
org study id: TV571-CNS-10018
nct id: NCT02184767
lead sponsor: 
has dmc: Yes
This study is to assess the pharmacokinetics of loxapine and will be using plasma
      concentration data obtained over 48 hours after administration of the study drug
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t)
time frame: 48 hours
measure: area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)
time frame: 48 hours
measure: ratio of AUC0-t to AUC0-inf (AUC0-t/AUC0-inf)
time frame: 48 hours
measure: maximum observed plasma drug concentration (Cmax)
time frame: 48 hours
measure: time to maximum observed concentration (tmax)
time frame: 48 hours
measure: apparent terminal elimination rate constant (Kel)
time frame: 48 hours
measure: elimination half-life (t½)
time frame: 48 hours
measure: apparent clearance (CL/F)
time frame: 48 hours
measure: volume of distribution (V/F)
time frame: 48 hours
measure: The palatability of ADASUVE will be performed using a visual analog scale (VAS)
time frame: 2 1/2 weeks
measure: Summary of participants with adverse events
time frame: 3 weeks
arm group label: ADASUVE®
arm group type: Experimental
description: oral inhalation using a single-use, hand-held, inhaler; dosage determined by the investigator according the participants weight
intervention type: Drug
intervention name: ADASUVE®
description: ADASUVE® 2.5, 5, or 10 mg
arm group label: ADASUVE®
other name: STACCATO® Loxapine for Inhalation
criteria: 
gender: All
minimum age: 10 Years
maximum age: 17 Years
healthy volunteers: No
last name: Sponsor Medical Expert, MD
role: Study Director
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Loxapine