<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/NCT03827642</url>
  </required_header>
  <id_info>
    <org_study_id>INS012-18-119</org_study_id>
    <nct_id>NCT03827642</nct_id>
  </id_info>
  <brief_title>A Study to Compare Bioavailability of Naloxone Nasal Spray, Naloxone Hydrochloride (HCl) Intravenous (IV) and Intramuscular Injection (IM) in Healthy Volunteers</brief_title>
  <official_title>A Phase 1, Open-Label, Randomized, Crossover, Comparative Bioavailability Study of Naloxone Nasal Spray and Naloxone Hydrochloride Intravenous and Intramuscular Injection in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>INSYS Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>INSYS Therapeutics 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of this study was to compare the bioavailability of two test formulations&#xD;
      of Naloxone Nasal Spray with the reference formulations of Naloxone HCl IV and IM injection&#xD;
      under fasted conditions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 23, 2018</start_date>
  <completion_date type="Actual">May 6, 2018</completion_date>
  <primary_completion_date type="Actual">May 6, 2018</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 the Curve From Time 0 to the Last Measured Concentration (AUC0-t) for Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC Extrapolated to Infinity (AUC0-inf) for Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) for Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Reach Maximum Plasma Concentration (Tmax) for Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time Prior to the First Measurable (Non-Zero) Concentration (Tlag) for Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination Rate Constant (λz) for Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination Half-Life (t1/2) of Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Partial Area Under the Concentration Curve (AUC) of Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 24 hours post-dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentrations of Unconjugated Naloxone</measure>
    <time_frame>Pre-dose and at multiple time points up to 2 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Day 1 to Day 14</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A serious AE (SAE) is any AE that results in death, is life threatening, requires hospitalization or prolongs existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Treatment Sequence A-D-C-B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Treatment A on Day 1 of Period 1, Treatment D on Day 1 of Period 2, Treatment C on Day 1 of Period 3 and Treatment B on Day 1 of Period 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Treatment Sequence B-C-D-A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Treatment B on Day 1 of Period 1, Treatment C on Day 1 of Period 2, Treatment D on Day 1 of Period 3 and Treatment A on Day 1 of Period 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: Treatment Sequence C-A-B-D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Treatment C on Day 1 of Period 1, Treatment A on Day 1 of Period 2, Treatment B on Day 1 of Period 3 and Treatment D on Day 1 of Period 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4: Treatment Sequence D-B-A-C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Treatment D on Day 1 of Period 1, Treatment B on Day 1 of Period 2, Treatment A on Day 1 of Period 3 and Treatment C on Day 1 of Period 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment A: Naloxone Nasal Spray</intervention_name>
    <description>Participants received naloxone nasal spray following a 10 hour fast.</description>
    <arm_group_label>Cohort 1: Treatment Sequence A-D-C-B</arm_group_label>
    <arm_group_label>Cohort 2: Treatment Sequence B-C-D-A</arm_group_label>
    <arm_group_label>Cohort 3: Treatment Sequence C-A-B-D</arm_group_label>
    <arm_group_label>Cohort 4: Treatment Sequence D-B-A-C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment B: Naloxone Nasal Spray</intervention_name>
    <description>Participants received naloxone nasal spray following a 10 hour fast.</description>
    <arm_group_label>Cohort 1: Treatment Sequence A-D-C-B</arm_group_label>
    <arm_group_label>Cohort 2: Treatment Sequence B-C-D-A</arm_group_label>
    <arm_group_label>Cohort 3: Treatment Sequence C-A-B-D</arm_group_label>
    <arm_group_label>Cohort 4: Treatment Sequence D-B-A-C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment C: Naloxone HCl Intravenous (IV) Injection</intervention_name>
    <description>Participants received naloxone HCl IV injection following a 10 hour fast.</description>
    <arm_group_label>Cohort 1: Treatment Sequence A-D-C-B</arm_group_label>
    <arm_group_label>Cohort 2: Treatment Sequence B-C-D-A</arm_group_label>
    <arm_group_label>Cohort 3: Treatment Sequence C-A-B-D</arm_group_label>
    <arm_group_label>Cohort 4: Treatment Sequence D-B-A-C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment D: Naloxone HCl Intramuscular (IM) Injection</intervention_name>
    <description>Participants received naloxone HCl IM injection following a 10 hour fast.</description>
    <arm_group_label>Cohort 1: Treatment Sequence A-D-C-B</arm_group_label>
    <arm_group_label>Cohort 2: Treatment Sequence B-C-D-A</arm_group_label>
    <arm_group_label>Cohort 3: Treatment Sequence C-A-B-D</arm_group_label>
    <arm_group_label>Cohort 4: Treatment Sequence D-B-A-C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A minimum body weight of 50 kg. Body mass index (BMI) between 18.0 and 32.0 kg/m2&#xD;
&#xD;
          -  A seated blood pressure between 90 and 140 mmHg systolic/50 and 90 mmHg diastolic&#xD;
&#xD;
          -  Female subjects had a negative serum β human chorionic gonadotropin (β-hCG) pregnancy&#xD;
             test at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A known allergy or history of significant adverse reaction to naloxone, other opioids&#xD;
             or related compounds, or to any of the excipients&#xD;
&#xD;
          -  Any documented clinically significant infection, injury, or illness within 1 month&#xD;
             prior to screening&#xD;
&#xD;
          -  An active malignancy of any type, or had been diagnosed with cancer within 5 years&#xD;
             prior to screening&#xD;
&#xD;
          -  A documented history of alcohol or drug abuse/dependence/misuse or narcotic analgesic&#xD;
             abuse/dependence/misuse within 2 years prior to screening&#xD;
&#xD;
          -  A positive urine test result for alcohol, drugs, or cotinine at screening or check-in&#xD;
&#xD;
          -  A condition that the investigator believed would have interfered with the ability to&#xD;
             provide informed consent or comply with study instructions, or that could confound the&#xD;
             interpretation of the study results or put the subject at undue risk&#xD;
&#xD;
          -  Used any opioids for 30 days prior to Day 1&#xD;
&#xD;
          -  Required treatment with monoamine oxidase inhibitors (MAOIs) within 30 days prior to&#xD;
             Day 1 and during the study.&#xD;
&#xD;
          -  Presence of an ongoing upper respiratory infection, rhinitis, rhinorrhea, or nasal&#xD;
             congestions&#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>Giovanni DeCastro</last_name>
    <role>Study Director</role>
    <affiliation>INSYS Therapeutics Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Worldwide Clinical Trials</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>January 31, 2019</last_update_submitted>
  <last_update_submitted_qc>January 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2019</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>Naloxone</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/NCT03827642
org study id: INS012-18-119
nct id: NCT03827642
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main objective of this study was to compare the bioavailability of two test formulations
      of Naloxone Nasal Spray with the reference formulations of Naloxone HCl IV and IM injection
      under fasted conditions.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Curve From Time 0 to the Last Measured Concentration (AUC0-t) for Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: AUC Extrapolated to Infinity (AUC0-inf) for Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Maximum Plasma Concentration (Cmax) for Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) for Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Time Prior to the First Measurable (Non-Zero) Concentration (Tlag) for Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Elimination Rate Constant (λz) for Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Elimination Half-Life (t1/2) of Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Partial Area Under the Concentration Curve (AUC) of Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Plasma Concentrations of Unconjugated Naloxone
time frame: Pre-dose and at multiple time points up to 2 hours post-dose
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Day 1 to Day 14
description: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A serious AE (SAE) is any AE that results in death, is life threatening, requires hospitalization or prolongs existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention.
arm group label: Cohort 1: Treatment Sequence A-D-C-B
arm group type: Experimental
description: Participants received Treatment A on Day 1 of Period 1, Treatment D on Day 1 of Period 2, Treatment C on Day 1 of Period 3 and Treatment B on Day 1 of Period 4.
arm group label: Cohort 2: Treatment Sequence B-C-D-A
arm group type: Experimental
description: Participants received Treatment B on Day 1 of Period 1, Treatment C on Day 1 of Period 2, Treatment D on Day 1 of Period 3 and Treatment A on Day 1 of Period 4.
arm group label: Cohort 3: Treatment Sequence C-A-B-D
arm group type: Experimental
description: Participants received Treatment C on Day 1 of Period 1, Treatment A on Day 1 of Period 2, Treatment B on Day 1 of Period 3 and Treatment D on Day 1 of Period 4.
arm group label: Cohort 4: Treatment Sequence D-B-A-C
arm group type: Experimental
description: Participants received Treatment D on Day 1 of Period 1, Treatment B on Day 1 of Period 2, Treatment A on Day 1 of Period 3 and Treatment C on Day 1 of Period 4.
intervention type: Drug
intervention name: Treatment A: Naloxone Nasal Spray
description: Participants received naloxone nasal spray following a 10 hour fast.
arm group label: Cohort 1: Treatment Sequence A-D-C-B
arm group label: Cohort 2: Treatment Sequence B-C-D-A
arm group label: Cohort 3: Treatment Sequence C-A-B-D
arm group label: Cohort 4: Treatment Sequence D-B-A-C
intervention type: Drug
intervention name: Treatment B: Naloxone Nasal Spray
description: Participants received naloxone nasal spray following a 10 hour fast.
arm group label: Cohort 1: Treatment Sequence A-D-C-B
arm group label: Cohort 2: Treatment Sequence B-C-D-A
arm group label: Cohort 3: Treatment Sequence C-A-B-D
arm group label: Cohort 4: Treatment Sequence D-B-A-C
intervention type: Drug
intervention name: Treatment C: Naloxone HCl Intravenous (IV) Injection
description: Participants received naloxone HCl IV injection following a 10 hour fast.
arm group label: Cohort 1: Treatment Sequence A-D-C-B
arm group label: Cohort 2: Treatment Sequence B-C-D-A
arm group label: Cohort 3: Treatment Sequence C-A-B-D
arm group label: Cohort 4: Treatment Sequence D-B-A-C
intervention type: Drug
intervention name: Treatment D: Naloxone HCl Intramuscular (IM) Injection
description: Participants received naloxone HCl IM injection following a 10 hour fast.
arm group label: Cohort 1: Treatment Sequence A-D-C-B
arm group label: Cohort 2: Treatment Sequence B-C-D-A
arm group label: Cohort 3: Treatment Sequence C-A-B-D
arm group label: Cohort 4: Treatment Sequence D-B-A-C
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Giovanni DeCastro
role: Study Director
affiliation: INSYS Therapeutics Inc
facility: 
country: United States
responsible party type: Sponsor
mesh term: Naloxone