<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/NCT02211625</url>
  </required_header>
  <id_info>
    <org_study_id>CP734-1002</org_study_id>
    <nct_id>NCT02211625</nct_id>
  </id_info>
  <brief_title>A Safety, Tolerability, PD and PK Study in Healthy Adults</brief_title>
  <official_title>A Two-Part Study to Evaluate the Safety, Tolerability, Pharmacodynamics And Pharmacokinetics of TRV734 in Healthy Adult Male and Female Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Trevena Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Trevena Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the safety, tolerability, pharmacodynamics&#xD;
      (PD) and pharmacokinetics (PK) of TRV734 given as a single dose (Part A) and as multiple&#xD;
      ascending doses (Part B) in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be conducted in two-parts enrolling a total of approximately 72 healthy volunteers.&#xD;
&#xD;
        -  Part A will assess the safety, tolerability, PD and PK of a 125mg dose of TRV734 in an&#xD;
           open-label, randomized, three-period crossover study in which subjects are fasted, fed a&#xD;
           standard meal, or fed a high-fat meal.&#xD;
&#xD;
        -  Part B of the trial will assess the safety, tolerability, PD and PK of multiple&#xD;
           ascending doses of TRV734 in a double blind, double dummy, randomized, active- and&#xD;
           placebo-controlled, adaptive study. Oxycodone immediate release (IR) 10 mg will be used&#xD;
           as a benchmark.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety</measure>
    <time_frame>7 days</time_frame>
    <description>Clinical safety data from adverse event reporting, clinical observations, 12-lead ECGs, cardiac telemetry monitoring, vital signs (blood pressure, heart rate, respiratory rate and oral temperature), oxygen saturation and safety laboratory tests.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect on pharmacodynamics of multiple ascending doses (Part B) of TRV734</measure>
    <time_frame>4 days</time_frame>
    <description>Change from baseline in: Pupillometry and Cold Pain Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on pharmacokinetics of multiple ascending (Part B) doses of TRV734</measure>
    <time_frame>4 days</time_frame>
    <description>From the plasma concentration-time data, the following PK parameters will be determined, as data permit: AUC, Cmax, tmax, t½,eff, Vss/F, C, AR, and CL/F. From the urine concentration data, the following will PK parameters will be determined, as data permit: %UR and CLR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on pharmacodynamics of 125mg dose or TRV734 (Part A) following various administration paradigms</measure>
    <time_frame>7 days</time_frame>
    <description>Change from baseline in: Pupillometry and Cold Pain Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on pharmacokinetics of 125mg dose of TRV734 (Part A) following various administration paradigms.</measure>
    <time_frame>7 days</time_frame>
    <description>From the plasma concentration-time data, the following PK parameters will be determined, as data permit: AUC, Cmax, tmax, t½,eff, Vss/F, C, AR, and CL/F. From the urine concentration data, the following will PK parameters will be determined, as data permit: %UR and CLR.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TRV734 125 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A, open-label will evaluate the the safety, PK and PD profile of a 125mg dose of TRV734 in which subjects are fasted, fed a standard meal, or fed a high-fat meal. Part A will also inform the dosing paradigm for Part B.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple ascending dose study, active and placebo comparators</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Part B will assess the safety, tolerability, PD and PK of TRV734. Subjects will be randomized in a ratio of 3:1:1 to receive either multiple doses of TRV734, oxycodone IR 10mg or placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Open-label TRV734 125 mg</intervention_name>
    <description>125 mg</description>
    <arm_group_label>TRV734 125 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TRV734 blinded</intervention_name>
    <description>blinded, multiple ascending dose</description>
    <arm_group_label>Multiple ascending dose study, active and placebo comparators</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxycodone IR 10 mg</intervention_name>
    <arm_group_label>Multiple ascending dose study, active and placebo comparators</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>TRV734-matched and oxycodone placebo</description>
    <arm_group_label>Multiple ascending dose study, active and placebo comparators</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy as determined by a responsible physician or trained qualified designee&#xD;
&#xD;
          -  Males (Part A) or males and females (Part B) between 18 &amp; 64 years of age, inclusive.&#xD;
             Females must be of non-childbearing&#xD;
&#xD;
          -  Capable of giving written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant conditions, or history of fainting or syncope&#xD;
&#xD;
          -  Medical or psychiatric illness&#xD;
&#xD;
          -  Major surgery within 4 weeks of screening&#xD;
&#xD;
          -  Known difficulty with obtaining intravenous access&#xD;
&#xD;
          -  Any ophthalmologic condition that could interfere with pupillometry&#xD;
&#xD;
          -  History of sensitivity to any of the investigational products, or known intolerance to&#xD;
             opioids or a history of medication or other allergy&#xD;
&#xD;
          -  Use of prescription or non prescription medications&#xD;
&#xD;
          -  History of drug abuse within 6 months of screening&#xD;
&#xD;
          -  Use of any illegal drug within 30 days of screening and throughout participation in&#xD;
             the study&#xD;
&#xD;
          -  History of smoking or use of nicotine containing products within 3 months of screening&#xD;
             and throughout participation in the study&#xD;
&#xD;
          -  Donation of blood or plasma within 4 weeks prior to dosing&#xD;
&#xD;
          -  Participation in a clinical trial and has received a medication within 30 days&#xD;
&#xD;
          -  Weight &lt;50 kg or BMI outside range of 18 - 32 kg/m2&#xD;
&#xD;
          -  Positive for HIV antibody, hepatitis B virus surface antigen, or hepatitis C virus&#xD;
&#xD;
          -  If male, unwillingness to abstain from sexual intercourse with a pregnant or lactating&#xD;
             woman and, if engaging in sexual intercourse with a female partner of childbearing&#xD;
             potential, use a condom and spermicide, in addition to having their female partner use&#xD;
             another form of contraception, and abstain from sperm donation&#xD;
&#xD;
          -  Part B Only:&#xD;
&#xD;
               -  Active dermatological condition or eczema on non-dominant hand.&#xD;
&#xD;
               -  Peripheral vascular disease&#xD;
&#xD;
               -  If female, of child bearing potential, pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Franck Skobieranda, MD</last_name>
    <role>Study Director</role>
    <affiliation>Trevena Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ICON Development Solutions</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>December 4, 2014</last_update_submitted>
  <last_update_submitted_qc>December 4, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 5, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy</keyword>
  <keyword>Pharmacodynamics (PD)</keyword>
  <keyword>Pharmacokinetics (PK)</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxycodone</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/NCT02211625
org study id: CP734-1002
nct id: NCT02211625
lead sponsor: 
has dmc: Yes
The primary objective of this study is to evaluate the safety, tolerability, pharmacodynamics
      (PD) and pharmacokinetics (PK) of TRV734 given as a single dose (Part A) and as multiple
      ascending doses (Part B) in healthy subjects.
This will be conducted in two-parts enrolling a total of approximately 72 healthy volunteers.

        -  Part A will assess the safety, tolerability, PD and PK of a 125mg dose of TRV734 in an
           open-label, randomized, three-period crossover study in which subjects are fasted, fed a
           standard meal, or fed a high-fat meal.

        -  Part B of the trial will assess the safety, tolerability, PD and PK of multiple
           ascending doses of TRV734 in a double blind, double dummy, randomized, active- and
           placebo-controlled, adaptive study. Oxycodone immediate release (IR) 10 mg will be used
           as a benchmark.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Safety
time frame: 7 days
description: Clinical safety data from adverse event reporting, clinical observations, 12-lead ECGs, cardiac telemetry monitoring, vital signs (blood pressure, heart rate, respiratory rate and oral temperature), oxygen saturation and safety laboratory tests.
measure: Effect on pharmacodynamics of multiple ascending doses (Part B) of TRV734
time frame: 4 days
description: Change from baseline in: Pupillometry and Cold Pain Test
measure: Effect on pharmacokinetics of multiple ascending (Part B) doses of TRV734
time frame: 4 days
description: From the plasma concentration-time data, the following PK parameters will be determined, as data permit: AUC, Cmax, tmax, t½,eff, Vss/F, C, AR, and CL/F. From the urine concentration data, the following will PK parameters will be determined, as data permit: %UR and CLR.
measure: Effect on pharmacodynamics of 125mg dose or TRV734 (Part A) following various administration paradigms
time frame: 7 days
description: Change from baseline in: Pupillometry and Cold Pain Test
measure: Effect on pharmacokinetics of 125mg dose of TRV734 (Part A) following various administration paradigms.
time frame: 7 days
description: From the plasma concentration-time data, the following PK parameters will be determined, as data permit: AUC, Cmax, tmax, t½,eff, Vss/F, C, AR, and CL/F. From the urine concentration data, the following will PK parameters will be determined, as data permit: %UR and CLR.
arm group label: TRV734 125 mg
arm group type: Experimental
description: Part A, open-label will evaluate the the safety, PK and PD profile of a 125mg dose of TRV734 in which subjects are fasted, fed a standard meal, or fed a high-fat meal. Part A will also inform the dosing paradigm for Part B.
arm group label: Multiple ascending dose study, active and placebo comparators
arm group type: Active Comparator
description: Part B will assess the safety, tolerability, PD and PK of TRV734. Subjects will be randomized in a ratio of 3:1:1 to receive either multiple doses of TRV734, oxycodone IR 10mg or placebo.
intervention type: Drug
intervention name: Open-label TRV734 125 mg
description: 125 mg
arm group label: TRV734 125 mg
intervention type: Drug
intervention name: TRV734 blinded
description: blinded, multiple ascending dose
arm group label: Multiple ascending dose study, active and placebo comparators
intervention type: Drug
intervention name: Oxycodone IR 10 mg
arm group label: Multiple ascending dose study, active and placebo comparators
intervention type: Drug
intervention name: Placebo
description: TRV734-matched and oxycodone placebo
arm group label: Multiple ascending dose study, active and placebo comparators
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Franck Skobieranda, MD
role: Study Director
affiliation: Trevena Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Oxycodone