<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/NCT02205554</url>
  </required_header>
  <id_info>
    <org_study_id>Syntrix-Omni-Pain-101</org_study_id>
    <secondary_id>R44DA027304</secondary_id>
    <nct_id>NCT02205554</nct_id>
  </id_info>
  <brief_title>Omnitram Pharmacokinetic Study In Healthy Volunteers</brief_title>
  <official_title>A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Triple Cross-Over Study Investigating The Safety, Oral Steady-State Pharmacokinetics, And Clinical Activity Of 20 Mg Omnitram And 50 Mg Tramadol In Normal Human Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Syntrix Biosystems, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Syntrix Biosystems, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the safety, pharmacokinetic properties (the&#xD;
      absorption, distribution and excretion), and analgesic activity of Omnitram (10 mg tablets),&#xD;
      Tramadol (Ultram, 50 mg tablet) following oral administration of 9 doses healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase 1, single-center, randomized, double-blind, placebo-controlled, three-period&#xD;
      cross-over study to compare the safety, steady-state oral pharmacokinetics, and clinical&#xD;
      activity of overencapsulated: 20 mg Omnitram (2x10 mg tablets), 50 mg Tramadol (1x50 mg&#xD;
      Ultram tablet), and placebo.&#xD;
&#xD;
      Forty male subjects in normal health, 21 to 55 years of age, will be randomized to three&#xD;
      parallel arms (N=~13 each) to ingest a total of 9 doses of Omnitram, Tramadol, or placebo in&#xD;
      a first treatment segment (one dose every 6 hours). Around the 9th dose blood samples are&#xD;
      collected to quantify plasma Tramadol and Metabolite 1 (M1) enantiomers. After the 9th dose,&#xD;
      pain tolerance is assessed with a cold pressor test (ice cold water immersion). After the 7th&#xD;
      dose abuse liability measures and pupil diameter will be assessed. Subjects will washout for&#xD;
      7 days after the first treatment segment and second treatment segment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Omnitram and Tramadol Steady State Maximum and Minimum Concentrations</measure>
    <time_frame>0.0, 1.0, 1.5, 2.0, 2.5, and 4.0 hours after the 9th dose of Omnitram and Tramadol.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>29 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cold Water Induced-Pain Reported On a 0 to 10 Scale</measure>
    <time_frame>On Study Day 2, Study Day 12, and Study Day 22, after the 9th dose of Omnitram, Tramadol, and placebo.</time_frame>
    <description>Subject immerses a hand in cold water for a maximum of 3 minutes and reports level of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abuse Liability Assessed With Visual Analogue Scales</measure>
    <time_frame>On Study Day 1, Study Day 11, and Study Day 21, after the 7th dose of Omnitram, Tramadol, and placebo.</time_frame>
    <description>Subjects read a question and respond by placing a mark on a visual analogue scale.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pupil Size</measure>
    <time_frame>On Study Day 1, Study Day 11, and Study Day 21, after the 7th dose of Omnitram, Tramadol, and placebo.</time_frame>
    <description>A pupilometer is used to measure eye pupil size.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Omnitram-Tramadol-Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Omnitram 20 mg every 6 hours for 9 doses, followed by Tramadol 50 mg every 6 hours for 9 doses, followed by Placebo every 6 hours for 9 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tramadol-Placebo-Omnitram</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tramadol 20 mg every 6 hours for 9 doses, followed by Placebo every 6 hours for 9 doses, followed by Omnitram 20 mg every 6 hours for 9 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo-Omnitram-Tramadol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo every 6 hours for 9 doses, followed by Omnitram 20 mg every 6 hours for 9 doses, followed by Tramadol 50 mg every 6 hours for 9 doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omnitram</intervention_name>
    <description>Nine 20 mg doses administered every 6 hours</description>
    <arm_group_label>Omnitram-Tramadol-Placebo</arm_group_label>
    <arm_group_label>Placebo-Omnitram-Tramadol</arm_group_label>
    <arm_group_label>Tramadol-Placebo-Omnitram</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tramadol</intervention_name>
    <description>Nine 50 mg doses administered every 6 hours.</description>
    <arm_group_label>Omnitram-Tramadol-Placebo</arm_group_label>
    <arm_group_label>Placebo-Omnitram-Tramadol</arm_group_label>
    <arm_group_label>Tramadol-Placebo-Omnitram</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Nine doses administered every 6 hours.</description>
    <arm_group_label>Omnitram-Tramadol-Placebo</arm_group_label>
    <arm_group_label>Placebo-Omnitram-Tramadol</arm_group_label>
    <arm_group_label>Tramadol-Placebo-Omnitram</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male with normal vital signs: systolic blood pressure &gt; 90 mm Hg and &lt; 140 mm&#xD;
             Hg; diastolic blood pressure &gt; 50 mm Hg and &lt; 90 mm Hg; pulse 50 to 100 beats per&#xD;
             minute; respiratory rate 12 to 20 breathes per minute&#xD;
&#xD;
          2. Between the ages of 21 and 55 years of age&#xD;
&#xD;
          3. Able and willing to give informed consent&#xD;
&#xD;
          4. Able to comply with all study procedures&#xD;
&#xD;
          5. Have adequate hematologic function as evidenced by the following screening results:&#xD;
&#xD;
               -  White Blood Cell (WBC) &gt;3,500/mm3 and &lt; 12,000/mm3;&#xD;
&#xD;
               -  Platelet Count &gt; 150,000/mm3 and &lt; 540,000/mm3;&#xD;
&#xD;
               -  Hemoglobin &gt; 12.5 gm/dL and &lt; 20.5 gm/dL.&#xD;
&#xD;
             Have adequate liver function as evidenced by the following screening results:&#xD;
&#xD;
               -  Aspartate transaminase (AST) ≤ 60 IU/L;&#xD;
&#xD;
               -  Alanine transaminase (ALT) ≤ 83 IU;&#xD;
&#xD;
               -  Alkaline Phosphatase ≤ 150 IU/L;&#xD;
&#xD;
               -  Total Bilirubin ≤ 1.2 mg/dL;&#xD;
&#xD;
               -  Prothrombin Time (PT) &lt; 1.2 upper limit of normal (ULN); Partial Thromboplastin&#xD;
                  Time (PTT) &lt; 1.2 ULN.&#xD;
&#xD;
          6. Electrocardiogram (ECG) within normal limits as determined by the PI&#xD;
&#xD;
          7. Have adequate renal function as evidenced by the following screening result:&#xD;
&#xD;
             Glomerular filtration rate (GFR) calculated by Cockcroft-Gault formula &gt;60 ml/min.&#xD;
&#xD;
             Urinalysis demonstrating &lt; +1 glucose, +1 ketones, and +1 protein&#xD;
&#xD;
          8. Negative urine test for substances of abuse, including opiates, per clinical research&#xD;
             unit (CRU) standards&#xD;
&#xD;
          9. Negative serology tests for HIV, hepatitis B surface antigen and hepatitis C virus&#xD;
             antibody&#xD;
&#xD;
         10. Body Mass Index (BMI) 19.0 to 32 kg/m&#xD;
&#xD;
         11. Cold pressor screening results as follows: 1) pain tolerance of &gt; 20 seconds and &lt;120&#xD;
             seconds&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Oral temperature &gt; 38°C or history of current illness&#xD;
&#xD;
          2. History of seizures, epilepsy, or recognized increase risk of seizure (e.g., head&#xD;
             trauma, metabolic disorders, alcohol or drug withdrawal)&#xD;
&#xD;
          3. History of cirrhosis or laboratory evidence of liver disease&#xD;
&#xD;
          4. Use of alcohol within 24 hours of day -1 until the end of the study; and grapefruit,&#xD;
             grapefruit-related citrus fruits (e.g., Seville oranges, pomelos), or grapefruit juice&#xD;
             or grapefruit-related juices, or other medication, within 7 days of study drug&#xD;
             administration and until the end of the study&#xD;
&#xD;
          5. History of previous anaphylaxis, severe allergic reaction to Tramadol, codeine, or&#xD;
             other opioid drugs&#xD;
&#xD;
          6. Use of monoamine oxidase (MAO) inhibitors (including linezolid), Serotonin Reuptake&#xD;
             Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and prescription or over-the&#xD;
             counter (OTC) medications known to induce or inhibit drug metabolism, including&#xD;
             cytochrome P450 2D6 (CYP2D6), and other drugs that may affect the serotonergic&#xD;
             neurotransmitter systems including, but not limited to, triptans, dextromethorphan,&#xD;
             tricyclic antidepressants, bupropion, lithium, tramadol, dietary supplements such as&#xD;
             tryptophan and St. John's Wort, and antipsychotics or other dopamine antagonists.&#xD;
             These restrictions are to be maintained from 14 days before study day -1, until the&#xD;
             subject completes the study&#xD;
&#xD;
          7. Any other unstable acute or chronic disease that could interfere with the evaluation&#xD;
             of the safety of the study drug as determined by the principal Investigator in&#xD;
             dialogue with the Sponsor Medical Monitor&#xD;
&#xD;
          8. Unlikely to comply with the study protocol&#xD;
&#xD;
          9. Known or suspected alcohol or drug abuse within the past 6 months&#xD;
&#xD;
         10. Received another investigational agent within 4 weeks of Day 0, or within five&#xD;
             half-lives of Day 0, whichever is longer; or receiving any other investigational agent&#xD;
             during this study&#xD;
&#xD;
         11. Any concurrent disease or condition that in the opinion of the investigator impairs&#xD;
             the subject's ability to complete the trial. Psychological, familial, sociological,&#xD;
             geographical or medical conditions which, in the Investigator's opinion, could&#xD;
             compromise compliance with the objectives and procedures of this protocol, or obscure&#xD;
             interpretation of the trial data&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shawn Searle, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PRA/CRI Lifetree Research Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stuart Kahn, MD</last_name>
    <role>Study Director</role>
    <affiliation>Syntrix Biosystems, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CRI Lifetree Research Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>October 13, 2014</last_update_submitted>
  <last_update_submitted_qc>October 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Analgesia</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Treatment</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tramadol</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/NCT02205554
org study id: Syntrix-Omni-Pain-101
secondary id: R44DA027304
nct id: NCT02205554
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to compare the safety, pharmacokinetic properties (the
      absorption, distribution and excretion), and analgesic activity of Omnitram (10 mg tablets),
      Tramadol (Ultram, 50 mg tablet) following oral administration of 9 doses healthy subjects.
A Phase 1, single-center, randomized, double-blind, placebo-controlled, three-period
      cross-over study to compare the safety, steady-state oral pharmacokinetics, and clinical
      activity of overencapsulated: 20 mg Omnitram (2x10 mg tablets), 50 mg Tramadol (1x50 mg
      Ultram tablet), and placebo.

      Forty male subjects in normal health, 21 to 55 years of age, will be randomized to three
      parallel arms (N=~13 each) to ingest a total of 9 doses of Omnitram, Tramadol, or placebo in
      a first treatment segment (one dose every 6 hours). Around the 9th dose blood samples are
      collected to quantify plasma Tramadol and Metabolite 1 (M1) enantiomers. After the 9th dose,
      pain tolerance is assessed with a cold pressor test (ice cold water immersion). After the 7th
      dose abuse liability measures and pupil diameter will be assessed. Subjects will washout for
      7 days after the first treatment segment and second treatment segment.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Omnitram and Tramadol Steady State Maximum and Minimum Concentrations
time frame: 0.0, 1.0, 1.5, 2.0, 2.5, and 4.0 hours after the 9th dose of Omnitram and Tramadol.
measure: Adverse events
time frame: 29 days
measure: Cold Water Induced-Pain Reported On a 0 to 10 Scale
time frame: On Study Day 2, Study Day 12, and Study Day 22, after the 9th dose of Omnitram, Tramadol, and placebo.
description: Subject immerses a hand in cold water for a maximum of 3 minutes and reports level of pain.
measure: Abuse Liability Assessed With Visual Analogue Scales
time frame: On Study Day 1, Study Day 11, and Study Day 21, after the 7th dose of Omnitram, Tramadol, and placebo.
description: Subjects read a question and respond by placing a mark on a visual analogue scale.
measure: Pupil Size
time frame: On Study Day 1, Study Day 11, and Study Day 21, after the 7th dose of Omnitram, Tramadol, and placebo.
description: A pupilometer is used to measure eye pupil size.
arm group label: Omnitram-Tramadol-Placebo
arm group type: Active Comparator
description: Omnitram 20 mg every 6 hours for 9 doses, followed by Tramadol 50 mg every 6 hours for 9 doses, followed by Placebo every 6 hours for 9 doses.
arm group label: Tramadol-Placebo-Omnitram
arm group type: Active Comparator
description: Tramadol 20 mg every 6 hours for 9 doses, followed by Placebo every 6 hours for 9 doses, followed by Omnitram 20 mg every 6 hours for 9 doses.
arm group label: Placebo-Omnitram-Tramadol
arm group type: Active Comparator
description: Placebo every 6 hours for 9 doses, followed by Omnitram 20 mg every 6 hours for 9 doses, followed by Tramadol 50 mg every 6 hours for 9 doses.
intervention type: Drug
intervention name: Omnitram
description: Nine 20 mg doses administered every 6 hours
arm group label: Omnitram-Tramadol-Placebo
arm group label: Placebo-Omnitram-Tramadol
arm group label: Tramadol-Placebo-Omnitram
intervention type: Drug
intervention name: Tramadol
description: Nine 50 mg doses administered every 6 hours.
arm group label: Omnitram-Tramadol-Placebo
arm group label: Placebo-Omnitram-Tramadol
arm group label: Tramadol-Placebo-Omnitram
intervention type: Drug
intervention name: Placebo
description: Nine doses administered every 6 hours.
arm group label: Omnitram-Tramadol-Placebo
arm group label: Placebo-Omnitram-Tramadol
arm group label: Tramadol-Placebo-Omnitram
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shawn Searle, MD
role: Principal Investigator
affiliation: PRA/CRI Lifetree Research Center
last name: Stuart Kahn, MD
role: Study Director
affiliation: Syntrix Biosystems, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tramadol