<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/NCT01689259</url>
  </required_header>
  <id_info>
    <org_study_id>TNX-CY-F103</org_study_id>
    <nct_id>NCT01689259</nct_id>
  </id_info>
  <brief_title>Comparative Pharmacokinetics and Safety of TNX-102 SL Tablets and Cyclobenzaprine Oral Tablet in Healthy Adults</brief_title>
  <official_title>A Single-Dose, Open-Label, Randomized, Parallel-Design Study of the Comparative Pharmacokinetics and Safety of TNX-102 2.4 mg SL Tablets (With Phosphate) at 2.4 mg and 4.8 mg, TNX-102-A 2.4 mg SL Tablets (Without Phosphate) at 2.4 mg and Cyclobenzaprine 5 mg Oral Tablets in Healthy Adults.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tonix Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tonix Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Very low dose (VLD) cyclobenzaprine at bedtime has shown promise as a treatment for&#xD;
      fibromyalgia, but the chemistry of cyclobenzaprine requires new formulation technology for&#xD;
      bedtime use. The present trial is designed to assess the safety and tolerability of TNX-102&#xD;
      2.4 mg SL Tablets (a new formulation of cyclobenzaprine designed to result in increased&#xD;
      dosage precision and decreased potential for morning grogginess) at 2.4 mg and 4.8 mg and to&#xD;
      compare the bio-availability of TNX-102 2.4 mg SL Tablets at 2.4 mg and 4.8 mg to that of&#xD;
      TNX-102-A 2.4 mg SL Tablets (without phosphate) at 2.4 mg and cyclobenzaprine (5 mg tablets).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">December 2013</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measured levels of cyclobenzaprine and norcyclobenzaprine in plasma and urine</measure>
    <time_frame>27 time points per period for blood assessment ; 3 pooled analyses in urine.</time_frame>
    <description>Blood samples will be taken per period: within 30 minutes pre-dose and 2, 3.5, 5, 10, 20, 30, and 45 minutes and 1, 2, 2.5, 3, 3.33, 3.67, 4, 4.33, 4.67, 5, 5.5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose. A single urine sample will be collected within 30 minutes pre-dose (one sample), and urine will be pooled from 0-24, 24-48 and 48-72 hours post-dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of TNX-102 SL Tablets at 2.4 mg and 4.8 mg.</measure>
    <time_frame>Continuously until the end (day 4) of the study period + Telephone follow-up 7-13 days after dosing (total duration: about 1 month)</time_frame>
    <description>Every adverse events occurring during the study period will be reported.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Adults</condition>
  <arm_group>
    <arm_group_label>SL TNX-102 at 2.4 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 x TNX-102 SL Tablets at 2.4 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SL TNX-102 at 4.8 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 x TNX-102 SL Tablets at 2.4 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SL TNX-102-A at 2.4 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 x TNX-102-A (without phosphate) SL Tablet at 2.4 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cyclobenzaprine tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 x 5 mg cyclobenzaprine oral tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SL TNX-102 at 2.4 mg</intervention_name>
    <description>1 TNX-102 SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing it.</description>
    <arm_group_label>SL TNX-102 at 2.4 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SL TNX-102 at 4.8 mg</intervention_name>
    <description>2 TNX-102 SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing them.</description>
    <arm_group_label>SL TNX-102 at 4.8 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SL TNX-102-A at 2.4 mg</intervention_name>
    <description>1 TNX-102-A SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing it.</description>
    <arm_group_label>SL TNX-102-A at 2.4 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclobenzaprine tablets</intervention_name>
    <description>1 x 5 mg cyclobenzaprine tablet, swallowed with 240 mL of room-temperature water</description>
    <arm_group_label>Cyclobenzaprine tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adults&#xD;
&#xD;
          -  Male or female&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
          -  18-65 years old&#xD;
&#xD;
          -  BMI &gt; 18.5 and &lt; 30.0&#xD;
&#xD;
          -  With medically acceptable form of contraception (female only)&#xD;
&#xD;
          -  With signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any clinically significant abnormality including ECG abnormalities or vital sign&#xD;
             abnormalities (systolic blood pressure &lt; 90 or &gt; 140 mmHg,&#xD;
&#xD;
          -  Diastolic blood pressure lower &lt; 50 or &gt; 90 mmHg, or heart rate &lt; 50 or &gt; 100 BPM)&#xD;
&#xD;
          -  Any abnormal laboratory test (including positivity for Hep B, Hep C, HIV, and&#xD;
&#xD;
          -  Hemoglobin &lt; 128 g/L (males) or &lt; 115 g/L (females) and hematocrit &lt; 0.37 L/L (males)&#xD;
             or &lt; 0.32 L/L (females))&#xD;
&#xD;
          -  History of alcohol or drug abuse or dependence within 1 year and/or positive drug,&#xD;
             cotinine, or alcohol tests&#xD;
&#xD;
          -  Use of any drug (within 30 days), supplement, or food (within 14 days) known to induce&#xD;
             or inhibit hepatic drug metabolism prior to study medication&#xD;
&#xD;
          -  Positive pregnancy test, breastfeeding or lactating&#xD;
&#xD;
          -  Use of medication other than hormonal contraceptives or topical products, including&#xD;
             OTC, natural health products, MAO inhibitors&#xD;
&#xD;
          -  Participation in an investigational study within 30 days prior to dosing&#xD;
&#xD;
          -  Donation of plasma (within 7 days), or donation or loss of blood of 50-499 mL (within&#xD;
             30 days), or of &gt; 499 mL (within 56 days) prior to dosing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Seth M. Lederman, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Tonix Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeffrey P. Kitrelle, MD</last_name>
    <role>Study Director</role>
    <affiliation>Tonix Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Denis Audet, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PharmaNet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PharmaNet, Inc.</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <zip>G1P 0A2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 14, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>September 24, 2014</last_update_submitted>
  <last_update_submitted_qc>September 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 26, 2014</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>Cyclobenzaprine</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/NCT01689259
org study id: TNX-CY-F103
nct id: NCT01689259
lead sponsor: 
has dmc: No
Very low dose (VLD) cyclobenzaprine at bedtime has shown promise as a treatment for
      fibromyalgia, but the chemistry of cyclobenzaprine requires new formulation technology for
      bedtime use. The present trial is designed to assess the safety and tolerability of TNX-102
      2.4 mg SL Tablets (a new formulation of cyclobenzaprine designed to result in increased
      dosage precision and decreased potential for morning grogginess) at 2.4 mg and 4.8 mg and to
      compare the bio-availability of TNX-102 2.4 mg SL Tablets at 2.4 mg and 4.8 mg to that of
      TNX-102-A 2.4 mg SL Tablets (without phosphate) at 2.4 mg and cyclobenzaprine (5 mg tablets).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Measured levels of cyclobenzaprine and norcyclobenzaprine in plasma and urine
time frame: 27 time points per period for blood assessment ; 3 pooled analyses in urine.
description: Blood samples will be taken per period: within 30 minutes pre-dose and 2, 3.5, 5, 10, 20, 30, and 45 minutes and 1, 2, 2.5, 3, 3.33, 3.67, 4, 4.33, 4.67, 5, 5.5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose. A single urine sample will be collected within 30 minutes pre-dose (one sample), and urine will be pooled from 0-24, 24-48 and 48-72 hours post-dose.
measure: Safety and tolerability of TNX-102 SL Tablets at 2.4 mg and 4.8 mg.
time frame: Continuously until the end (day 4) of the study period + Telephone follow-up 7-13 days after dosing (total duration: about 1 month)
description: Every adverse events occurring during the study period will be reported.
arm group label: SL TNX-102 at 2.4 mg
arm group type: Experimental
description: 1 x TNX-102 SL Tablets at 2.4 mg
arm group label: SL TNX-102 at 4.8 mg
arm group type: Experimental
description: 2 x TNX-102 SL Tablets at 2.4 mg
arm group label: SL TNX-102-A at 2.4 mg
arm group type: Experimental
description: 1 x TNX-102-A (without phosphate) SL Tablet at 2.4 mg
arm group label: Cyclobenzaprine tablets
arm group type: Active Comparator
description: 1 x 5 mg cyclobenzaprine oral tablet
intervention type: Drug
intervention name: SL TNX-102 at 2.4 mg
description: 1 TNX-102 SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing it.
arm group label: SL TNX-102 at 2.4 mg
intervention type: Drug
intervention name: SL TNX-102 at 4.8 mg
description: 2 TNX-102 SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing them.
arm group label: SL TNX-102 at 4.8 mg
intervention type: Drug
intervention name: SL TNX-102-A at 2.4 mg
description: 1 TNX-102-A SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing it.
arm group label: SL TNX-102-A at 2.4 mg
intervention type: Drug
intervention name: Cyclobenzaprine tablets
description: 1 x 5 mg cyclobenzaprine tablet, swallowed with 240 mL of room-temperature water
arm group label: Cyclobenzaprine tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Seth M. Lederman, MD
role: Study Chair
affiliation: Tonix Pharmaceuticals, Inc.
last name: Jeffrey P. Kitrelle, MD
role: Study Director
affiliation: Tonix Pharmaceuticals, Inc.
last name: Denis Audet, MD
role: Principal Investigator
affiliation: PharmaNet
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Cyclobenzaprine