<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/NCT01731730</url>
  </required_header>
  <id_info>
    <org_study_id>ADYX-002</org_study_id>
    <nct_id>NCT01731730</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Safety/Efficacy of a Single Pre-Op Dose of AYX1 Injection to Treat Pain After Knee Replacement Surgery</brief_title>
  <official_title>Study to Evaluate the Safety &amp; Efficacy of a Single Intrathecal Pre-Operative Administration of AYX1 Injection at Two Dose Levels Compared to Placebo in Patients Undergoing Unilateral Total Knee Arthroplasty (TKA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adynxx, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adynxx, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this proof of concept study are to evaluate the safety and preventive&#xD;
      analgesic efficacy of a single preoperative intrathecal administration of AYX1 Injection in&#xD;
      patients undergoing unilateral total knee arthroplasty.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain with walking during 5 meter walk test</measure>
    <time_frame>0-48 hours after surgery</time_frame>
    <description>Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 5 meter walk test during inpatient stay 0-48 hours</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pain with walking during 15 meter walk test</measure>
    <time_frame>From hospital discharge to Day 28</time_frame>
    <description>Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 15 meter walk test during outpatient period up to Day 28</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total use of opioid medications (morphine equivalents) during hospital stay</measure>
    <time_frame>0-48 hours after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total use of opioid medications (morphine equivalents) post-discharge to Day 28</measure>
    <time_frame>From hospital discharge to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain with 45 degrees of knee flexion</measure>
    <time_frame>0-48 hours after surgery</time_frame>
    <description>Mean pain rating on the Numerical Rating Scale (NRS) for 45 degrees active knee flexion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain with 90 degrees of knee flexion</measure>
    <time_frame>From 7 to 28 days after surgery</time_frame>
    <description>Mean pain rating on the Numerical Rating Scale (NRS) for 90 degrees active knee flexion</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Brief Pain Inventory functional interference scores at Days 7, 14, 21, 28, and 42</measure>
    <time_frame>7 to 42 days after surgery</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">102</enrollment>
  <condition>Postsurgical Pain</condition>
  <arm_group>
    <arm_group_label>Placebo (Vehicle) Injection</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single Intrathecal (spinal) administration of Placebo Injection just prior to intrathecal administration of spinal anesthetic for knee surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AYX1 Injection 110 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Intrathecal (spinal) administration of AYX1 Injection (110 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AYX1 Injection 330 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Intrathecal (spinal) administration of AYX1 Injection (330 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Injection</intervention_name>
    <description>3mL solution for intrathecal injection; Vehicle formulation designed to mimic AYX1 Injection (with no active drug)</description>
    <arm_group_label>Placebo (Vehicle) Injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AYX1 Injection 110 mg</intervention_name>
    <description>3mL solution for intrathecal injection with 110 mg of AYX1</description>
    <arm_group_label>AYX1 Injection 110 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AYX1 Injection 330 mg</intervention_name>
    <description>3mL solution for intrathecal injection with 330 mg of AYX1</description>
    <arm_group_label>AYX1 Injection 330 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Scheduled to undergo primary unilateral TKA for painful osteoarthritis&#xD;
&#xD;
          -  American Society of Anesthesiologists Physical Status Classification System ≤ 3&#xD;
&#xD;
          -  Medically stable as determined by the Investigator based on pre-study medical history,&#xD;
             physical/neurological examination, clinical lab tests, and 12-lead ECG findings&#xD;
&#xD;
          -  Body mass index of 18-40 kg/m2&#xD;
&#xD;
          -  Stable medical regimen for ≥ 1 month before randomization&#xD;
&#xD;
          -  Able to read and understand study instructions in English, and willing and able to&#xD;
             comply with all study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  More than 2 other current focal areas of pain, none greater in intensity than the&#xD;
             target knee and no other active chronic pain conditions that would compromise&#xD;
             operative knee pain evaluation&#xD;
&#xD;
          -  Inflammatory arthridities (i.e., rheumatoid arthritis, lupus, ankylosing spondylitis,&#xD;
             psoriatic arthritis, gout)&#xD;
&#xD;
          -  Operative arthroscopy in the surgical knee in the last 6 months, or other prior&#xD;
             surgery in either knee in the last 12 months, except for diagnostic arthroscopy&#xD;
&#xD;
          -  Planned use of any of the following for TKA: general endotracheal anesthesia (GETA),&#xD;
             peripheral nerve block (i.e., femoral nerve block), neuroaxial (intrathecal or&#xD;
             epidural) opioids postoperatively, or knee capsule injections&#xD;
&#xD;
          -  Received aspirin within 1 week of randomization, or any nonsteroidal anti-inflammatory&#xD;
             drug (NSAID) within 5 half-lives prior to randomization, or planned use of NSAIDS&#xD;
             post-operatively through Day 28&#xD;
&#xD;
          -  Use of more than 20 mg per day (on average) of oral morphine or its equivalent within&#xD;
             1 month prior to randomization&#xD;
&#xD;
          -  Use of adjuvant analgesics for chronic pain control (i.e., gabapentin, pregabalin)&#xD;
             during the month prior to randomization or planned use post-operatively through Day 28&#xD;
&#xD;
          -  Daily use of benzodiazepines in the 3 months prior to randomization (unless used for&#xD;
             sleep and dosage will be consistent after surgery)&#xD;
&#xD;
          -  Use of systemic corticosteroids (does not include inhaled steroids) within 3 months or&#xD;
             intra-articular steroid injections within 1 month prior to randomization, or planned&#xD;
             use of either post-op through Day 28&#xD;
&#xD;
          -  Treatment with antibiotics or antivirals (EXCEPTION: topical treatments),&#xD;
             immunosuppressives, antipsychotics, anticholinergics, or anticonvulsants within 1&#xD;
             month of randomization, with the exception of prescribed pre-surgical prophylactic&#xD;
             antibiotics, and aspirin for cardiac prophylaxis (as long as discontinued within 1&#xD;
             week of randomization&#xD;
&#xD;
          -  Current neurologic disorder, which could confound the assessment of pain (i.e.,&#xD;
             Parkinson's, Multiple Sclerosis)&#xD;
&#xD;
          -  Current active depression symptoms&#xD;
&#xD;
          -  Has had a change in dose or regimen of SSRIs or SNRIs for depression within 1 month of&#xD;
             randomization&#xD;
&#xD;
          -  Mini Mental State Exam score &lt; 24 at screening&#xD;
&#xD;
          -  Current history of insulin dependent diabetes mellitus, or autoimmune conditions&#xD;
&#xD;
          -  Severe chronic obstructive or restrictive pulmonary disease, current diagnosis of&#xD;
             obstructive sleep apnea documented by a sleep laboratory study, or current home use of&#xD;
             continuous positive airway pressure (CPAP) or bi-level positive airway pressure&#xD;
             (BIPAP)&#xD;
&#xD;
          -  Current evidence of alcohol abuse or history of alcohol-related complications within 1&#xD;
             year of randomization&#xD;
&#xD;
          -  Known or suspected history of illicit drug abuse within 1 year before randomization,&#xD;
             current or planned use of medical marijuana, or history of opioid dependence within 2&#xD;
             years before randomization&#xD;
&#xD;
          -  Any malignancy within the past year, with the exception of basal cell carcinoma or&#xD;
             uncomplicated or stable skin cancers documented to not require further or immediate&#xD;
             treatment&#xD;
&#xD;
          -  Women who are pregnant or nursing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Donald C Manning, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Adynxx, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Sheffield</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boynton Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Altoona</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nassau Bay</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Odessa</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <disposition_first_submitted>January 14, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>January 14, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">January 27, 2015</disposition_first_posted>
  <last_update_submitted>January 14, 2015</last_update_submitted>
  <last_update_submitted_qc>January 14, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 27, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Postsurgical pain</keyword>
  <keyword>Total knee arthroplasty</keyword>
  <keyword>Total knee replacement</keyword>
  <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/NCT01731730
org study id: ADYX-002
nct id: NCT01731730
lead sponsor: 
has dmc: Yes
The objectives of this proof of concept study are to evaluate the safety and preventive
      analgesic efficacy of a single preoperative intrathecal administration of AYX1 Injection in
      patients undergoing unilateral total knee arthroplasty.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Pain with walking during 5 meter walk test
time frame: 0-48 hours after surgery
description: Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 5 meter walk test during inpatient stay 0-48 hours
measure: Pain with walking during 15 meter walk test
time frame: From hospital discharge to Day 28
description: Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 15 meter walk test during outpatient period up to Day 28
measure: Total use of opioid medications (morphine equivalents) during hospital stay
time frame: 0-48 hours after surgery
measure: Total use of opioid medications (morphine equivalents) post-discharge to Day 28
time frame: From hospital discharge to Day 28
measure: Pain with 45 degrees of knee flexion
time frame: 0-48 hours after surgery
description: Mean pain rating on the Numerical Rating Scale (NRS) for 45 degrees active knee flexion
measure: Pain with 90 degrees of knee flexion
time frame: From 7 to 28 days after surgery
description: Mean pain rating on the Numerical Rating Scale (NRS) for 90 degrees active knee flexion
measure: Brief Pain Inventory functional interference scores at Days 7, 14, 21, 28, and 42
time frame: 7 to 42 days after surgery
arm group label: Placebo (Vehicle) Injection
arm group type: Placebo Comparator
description: Single Intrathecal (spinal) administration of Placebo Injection just prior to intrathecal administration of spinal anesthetic for knee surgery
arm group label: AYX1 Injection 110 mg
arm group type: Experimental
description: Single Intrathecal (spinal) administration of AYX1 Injection (110 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery
arm group label: AYX1 Injection 330 mg
arm group type: Experimental
description: Single Intrathecal (spinal) administration of AYX1 Injection (330 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery
intervention type: Drug
intervention name: Placebo Injection
description: 3mL solution for intrathecal injection; Vehicle formulation designed to mimic AYX1 Injection (with no active drug)
arm group label: Placebo (Vehicle) Injection
intervention type: Drug
intervention name: AYX1 Injection 110 mg
description: 3mL solution for intrathecal injection with 110 mg of AYX1
arm group label: AYX1 Injection 110 mg
intervention type: Drug
intervention name: AYX1 Injection 330 mg
description: 3mL solution for intrathecal injection with 330 mg of AYX1
arm group label: AYX1 Injection 330 mg
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Donald C Manning, MD, PhD
role: Study Director
affiliation: Adynxx, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative