<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/NCT02992041</url>
  </required_header>
  <id_info>
    <org_study_id>VVZ149-POP-P2-US002</org_study_id>
    <nct_id>NCT02992041</nct_id>
  </id_info>
  <brief_title>Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injections for Post-Operative Pain Following Laparoscopic Colorectomy</brief_title>
  <official_title>A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Dose Finding Study to Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injections for Post-Operative Pain Following Laparoscopic Colorectal Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vivozon, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vivozon, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this phase 2 study is to evaluate the efficacy and safety of an analgesic drug&#xD;
      candidate, VVZ-149 Injections. The study is designed as randomized, double-blind, parallel,&#xD;
      placebo-controlled study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      VVZ-149 is a dual antagonist of GlyT2 and 5HT2A. GlyT2 blockage increases inhibitory synaptic&#xD;
      transmission by glycine in the spinal cord, resulting in a reduction of pain transmissions to&#xD;
      the brain. 5HT2A blockage decreases descending serotonergic facilitatory modulation on pain&#xD;
      transmission by the brain and reduces nociceptor activation in peripheral nerves, which are&#xD;
      primary sources of pain in post-surgical pain. VVZ-149 has been shown to have comparable&#xD;
      efficacy to morphine in well controlled (blind, complete randomization with a positive&#xD;
      control) animal studies using rat models of post-operative pain and formalin-induced pain.&#xD;
      The PK/PD study in animals indicates that therapeutic plasma concentration in human subjects&#xD;
      will be 600-1,900 ng/ml. A clinical Phase 1 study performed in healthy subjects has shown no&#xD;
      clinically significant adverse events up to a plasma concentration level of 3,261 ng/ml other&#xD;
      than brief symptoms of mild nausea or dizziness, and mild somnolence when the plasma exposure&#xD;
      level is more than 2,000 ng/ml. A clinical Phase 2 study performed in laparoscopic&#xD;
      gastrectomy patients showed that patients who received VVZ-149 had reduced opioid consumption&#xD;
      after surgery compared to those who received placebo, without any significant drug-related&#xD;
      adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 27, 2016</start_date>
  <completion_date type="Actual">April 26, 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>area under the curve (AUC) of Pain Intensity</measure>
    <time_frame>0hr=start of PCA, 1hr and 2 hours</time_frame>
    <description>area under the curve (AUC) of Pain Intensity using Numeric Pain Rating Scale (NRS, 0-10 at rest) measured up to 2 hours post-initiation of PCA</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Opioid Consumption up to 24 hours post-dosing of study drug</measure>
    <time_frame>0-2, 2-4, 4-6, 6-8, 8-10, 10-12, and 12-24 hours</time_frame>
    <description>Total amount of hydromorphone (including rescue doses) consumption up to 24 hours after starting PCA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Intensity (Numeric Pain Rating Scale, NRS)</measure>
    <time_frame>0, 1, 2, 4, 6, 8, 10, 12, and 24 hours</time_frame>
    <description>Pain Intensity (NRS at rest) measured up to 24 hours post-initiation of PCA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global measurement of subject satisfaction with study medication</measure>
    <time_frame>8 and 24 hours post-initiation of PCA</time_frame>
    <description>Global assessment of subject satisfaction with analgesic management using a 5-point scale (0-4)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Richmond Agitation Sedation Scale (RASS)</measure>
    <time_frame>0, 1, 2, 4, 6, 8, 10, 12, and 24 hours post-initiation of PCA</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Depression Assessment</measure>
    <time_frame>0, 1, 2, 4, 6, 8, 10, 12, 24 hours post-initiation of PCA and within 10 minutes prior to administering any rescue doses of hydromorphone</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Nausea and Vomiting scale (PONV)</measure>
    <time_frame>0, 4, 8, 12, and 24 hours post-initiation of PCA</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>Post-Operative Pain</condition>
  <arm_group>
    <arm_group_label>Lower dose VVZ-149 Injections</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Higher dose VVZ-149 Injections</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VVZ-149 Injections</intervention_name>
    <description>IV infusion of 900 or 1100 mg of VVZ-149</description>
    <arm_group_label>Higher dose VVZ-149 Injections</arm_group_label>
    <arm_group_label>Lower dose VVZ-149 Injections</arm_group_label>
    <other_name>Opiranserin Injections</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>IV infusion of 0 mg of VVZ-149</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects undergoing planned laparoscopic colorectal surgery.&#xD;
&#xD;
          -  Ability to provide written informed consent.&#xD;
&#xD;
          -  Ability to understand study procedures and communicate clearly with the investigator&#xD;
             and staff.&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) risk class of I to III.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        &lt;Surgical Factors&gt;&#xD;
&#xD;
          -  Emergency or unplanned surgery.&#xD;
&#xD;
          -  Repeat operation (e.g., previous surgery within 30 days for same condition).&#xD;
&#xD;
          -  Cancer-related condition causing preoperative pain in site of surgery.&#xD;
&#xD;
          -  Surgical duration (from incision to end of closure) &gt; 5 hours.&#xD;
&#xD;
        &lt;Subject Characteristics&gt;&#xD;
&#xD;
          -  Women with childbearing potential (age 18-55) must undergo blood pregnancy test at&#xD;
             screening and then a urine pregnancy test preoperatively on day of surgery. Women with&#xD;
             a positive pregnancy test will be excluded. Women of childbearing potential must agree&#xD;
             to use at least one effective contraceptive method upon enrollment and for 30 days&#xD;
             following the last dose of the investigational product.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Chronic pain diagnosis (e.g., ongoing pain at baseline with NRS ≥ 4/10).&#xD;
&#xD;
          -  Unstable or poorly controlled psychiatric condition (e.g., untreated PTSD, anxiety, or&#xD;
             depression) Subjects who take stable doses of antidepressants and anti-anxiety drugs,&#xD;
             or procedure-related anti-anxiety drugs may be included.&#xD;
&#xD;
          -  Unstable or acute medical condition (e.g., unstable angina, congestive heart failure,&#xD;
             renal failure, hepatic failure, AIDS).&#xD;
&#xD;
          -  Body weight under 55 kg.&#xD;
&#xD;
        &lt;Drug, Alcohol, and Pharmacological Considerations&gt;&#xD;
&#xD;
          -  Renal or hepatic impairment.&#xD;
&#xD;
          -  History of alcohol, opiate or other drug abuse or dependence within 12 months prior to&#xD;
             Screening (TICS alcohol/drug screen will be performed at Screening).&#xD;
&#xD;
          -  Ongoing or recent (within 30 days prior to surgery) use of opioids or antipsychotics.&#xD;
             However, subjects who receive procedure-related opioids (i.e., for a preoperative&#xD;
             colonoscopy) may be included.&#xD;
&#xD;
          -  Alcohol consumption within 24 hours of surgery.&#xD;
&#xD;
          -  Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 24 hours&#xD;
             of surgery. Exception: use of aspirin for cardiovascular prophylaxis is acceptable.&#xD;
&#xD;
          -  Use of herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, jin bu&#xD;
             huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) within 7 days prior to&#xD;
             surgery.&#xD;
&#xD;
        &lt;Anesthetic and Other Exclusion Considerations&gt;&#xD;
&#xD;
          -  Use of neuraxial or regional anesthesia related to the surgery.&#xD;
&#xD;
          -  Use of local anesthetic wound infiltration &gt; 20 ml of 1% lidocaine&#xD;
&#xD;
          -  Use of ketamine, gabapentin, pregabalin, or lidocaine (&gt;1 mg/kg) intra or&#xD;
             peri-operatively, or within 24 hours of surgery.&#xD;
&#xD;
          -  Subjects with known allergies to hydromorphone.&#xD;
&#xD;
          -  Subjects who received another investigational drug within 30 days of scheduled&#xD;
             surgery.&#xD;
&#xD;
          -  Subjects who have long PR (&gt;200 msec) or prolonged QTc (&gt; 450 msec for males and &gt; 470&#xD;
             msec for females) at Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <disposition_first_submitted>August 11, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>August 18, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 25, 2020</disposition_first_posted>
  <last_update_submitted>August 18, 2020</last_update_submitted>
  <last_update_submitted_qc>August 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02992041
org study id: VVZ149-POP-P2-US002
nct id: NCT02992041
lead sponsor: 
has dmc: No
The purpose of this phase 2 study is to evaluate the efficacy and safety of an analgesic drug
      candidate, VVZ-149 Injections. The study is designed as randomized, double-blind, parallel,
      placebo-controlled study.
VVZ-149 is a dual antagonist of GlyT2 and 5HT2A. GlyT2 blockage increases inhibitory synaptic
      transmission by glycine in the spinal cord, resulting in a reduction of pain transmissions to
      the brain. 5HT2A blockage decreases descending serotonergic facilitatory modulation on pain
      transmission by the brain and reduces nociceptor activation in peripheral nerves, which are
      primary sources of pain in post-surgical pain. VVZ-149 has been shown to have comparable
      efficacy to morphine in well controlled (blind, complete randomization with a positive
      control) animal studies using rat models of post-operative pain and formalin-induced pain.
      The PK/PD study in animals indicates that therapeutic plasma concentration in human subjects
      will be 600-1,900 ng/ml. A clinical Phase 1 study performed in healthy subjects has shown no
      clinically significant adverse events up to a plasma concentration level of 3,261 ng/ml other
      than brief symptoms of mild nausea or dizziness, and mild somnolence when the plasma exposure
      level is more than 2,000 ng/ml. A clinical Phase 2 study performed in laparoscopic
      gastrectomy patients showed that patients who received VVZ-149 had reduced opioid consumption
      after surgery compared to those who received placebo, without any significant drug-related
      adverse events.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: area under the curve (AUC) of Pain Intensity
time frame: 0hr=start of PCA, 1hr and 2 hours
description: area under the curve (AUC) of Pain Intensity using Numeric Pain Rating Scale (NRS, 0-10 at rest) measured up to 2 hours post-initiation of PCA
measure: Opioid Consumption up to 24 hours post-dosing of study drug
time frame: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, and 12-24 hours
description: Total amount of hydromorphone (including rescue doses) consumption up to 24 hours after starting PCA
measure: Pain Intensity (Numeric Pain Rating Scale, NRS)
time frame: 0, 1, 2, 4, 6, 8, 10, 12, and 24 hours
description: Pain Intensity (NRS at rest) measured up to 24 hours post-initiation of PCA
measure: Global measurement of subject satisfaction with study medication
time frame: 8 and 24 hours post-initiation of PCA
description: Global assessment of subject satisfaction with analgesic management using a 5-point scale (0-4)
measure: Richmond Agitation Sedation Scale (RASS)
time frame: 0, 1, 2, 4, 6, 8, 10, 12, and 24 hours post-initiation of PCA
measure: Respiratory Depression Assessment
time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24 hours post-initiation of PCA and within 10 minutes prior to administering any rescue doses of hydromorphone
measure: Post-Operative Nausea and Vomiting scale (PONV)
time frame: 0, 4, 8, 12, and 24 hours post-initiation of PCA
arm group label: Lower dose VVZ-149 Injections
arm group type: Experimental
arm group label: Higher dose VVZ-149 Injections
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: VVZ-149 Injections
description: IV infusion of 900 or 1100 mg of VVZ-149
arm group label: Higher dose VVZ-149 Injections
arm group label: Lower dose VVZ-149 Injections
other name: Opiranserin Injections
intervention type: Drug
intervention name: Placebo
description: IV infusion of 0 mg of VVZ-149
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative