<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/NCT02263222</url>
  </required_header>
  <id_info>
    <org_study_id>P13-02</org_study_id>
    <nct_id>NCT02263222</nct_id>
  </id_info>
  <brief_title>A Feasibility Dose-escalating Study of MDT-10013 for Acute Postoperative Pain Following Total Knee Arthroplasty</brief_title>
  <official_title>A Feasibility Dose-escalating Study to Evaluate the Tolerability and Systemic Exposure of MDT-10013 Plus Routine Care in the Treatment of Acute Postoperative Pain Following Total Knee Arthroplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medtronic Spinal and Biologics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medtronic Spinal and Biologics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label dose-escalating study to evaluate the tolerability and systemic&#xD;
      exposure of MDT-10013 in men and women at least 18 years of age who are undergoing primary&#xD;
      unilateral TKA.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>February 2016</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) parameters of MDT-10013--maximum plasma concentration observed (Cmax)</measure>
    <time_frame>From day 1 to day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) parameters of MDT-10013--time to maximum plasma concentration observed (tmax)</measure>
    <time_frame>From day 1 to day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) parameters of MDT-10013--area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>From day 1 to day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of study drug/treatment-related serious adverse events (SAEs)</measure>
    <time_frame>up to 3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Summed pain intensity scores at rest</measure>
    <time_frame>up to 120 hours</time_frame>
    <description>Summed pain intensity scores (calculated as a time-weighted average) by using an 11-point (0 to 10) numerical rating scale (NRS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed pain intensity scores over 2 to 48 hours (SPI-48) with activity</measure>
    <time_frame>up to 48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aggregate dosage of all opioid analgesia</measure>
    <time_frame>0 to 24 hours and 0 to 48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total use of opioid analgesia</measure>
    <time_frame>From 48 hours through Day 6/120 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first use of opioid analgesia defined as the time from Time 0 to the first use of opioid analgesia.</measure>
    <time_frame>Time 0 is defined as the initiation of arthrotomy closure to the first opioid analgesia use</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject global evaluation of study treatment</measure>
    <time_frame>up to 10-14 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Post-operation Pain</condition>
  <arm_group>
    <arm_group_label>MDT-10013</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive MDT-10013.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MDT-10013</intervention_name>
    <arm_group_label>MDT-10013</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Is male or female at least 18 years of age&#xD;
&#xD;
          2. Has a body mass index from 18 kg/m2 to 40 kg/m2&#xD;
&#xD;
          3. Is scheduled to undergo standard primary (first-time) unilateral TKA surgery (due to&#xD;
             osteoarthritis) with or without patellar resurfacing. Standard conventional&#xD;
             instrumentation and cemented components must be used and the surgery shall be&#xD;
             conducted under spinal anesthesia.&#xD;
&#xD;
          4. Females must meet the following criteria:&#xD;
&#xD;
               -  Is of nonchildbearing potential, defined as any woman who has undergone surgical&#xD;
                  sterilization or is more than 2 years postmenopausal&#xD;
&#xD;
               -  If of childbearing potential, may be enrolled if pregnancy test results are&#xD;
                  negative at Screening and if she is routinely using an effective method of birth&#xD;
                  control with a low failure rate (i.e., hormonal contraception, intrauterine&#xD;
                  device, condoms in combination with a spermicidal cream, or total sexual&#xD;
                  abstinence).&#xD;
&#xD;
               -  May not be pregnant or lactating&#xD;
&#xD;
          5. Has read, understood, and signed the informed consent before study entry&#xD;
&#xD;
          6. Is mentally competent, reliable, and cooperative to undergo all visits and procedures&#xD;
             scheduled in the study protocol and to record the required information.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has had previous spinal surgery or other contraindications that preclude use of spinal&#xD;
             anesthesia or is not indicated for surgery because of an inflammatory process or risk&#xD;
             of infection or delayed wound healing (e.g., autoimmune disorder)&#xD;
&#xD;
          2. Is scheduled to undergo a concurrent surgical procedure (e.g., bilateral TKA)&#xD;
&#xD;
          3. Has a concurrent painful condition or surgery that may require analgesic treatment&#xD;
             (such as a nonsteroidal antiinflammatory drug [NSAID] or opioid) in the postsurgical&#xD;
             period for pain not strictly related to the TKA, and that may confound postsurgical&#xD;
             assessments&#xD;
&#xD;
          4. Has a history of allergy or hypersensitivity to the components in the investigational&#xD;
             product or to the routine care medications&#xD;
&#xD;
          5. Has current orthostatic hypotension (i.e., systolic blood pressure decrease of at&#xD;
             least 20 mmHg or diastolic blood pressure decrease of at least 10 mmHg or an increase&#xD;
             in heart rate of 20 beats per minute within 3 minutes of standing)&#xD;
&#xD;
          6. Has any clinically significant cardiovascular condition as evidenced by physical&#xD;
             examination, medical history, and/or baseline electrocardiogram (ECG), including&#xD;
             inadequately controlled hypertension&#xD;
&#xD;
          7. Has evidence of bradycardia as shown by heart rate of &lt;50 beats per minute via&#xD;
             screening ECG&#xD;
&#xD;
          8. In the investigator's opinion, subject is not a suitable candidate for study treatment&#xD;
             and/or has any poorly controlled or serious medical conditions, psychiatric illnesses,&#xD;
             or clinically significant laboratory values that the investigator suspects could&#xD;
             compromise the subject's safety or the scientific integrity of the study (e.g., human&#xD;
             immunodeficiency virus [HIV], hepatitis B or C [hep B, hep C])&#xD;
&#xD;
          9. Has presence or history of local or systemic malignant disease in the past 5 years&#xD;
             (history of basal cell carcinoma will be allowed)&#xD;
&#xD;
         10. Has undergone prior open surgery in the affected knee&#xD;
&#xD;
         11. Has impaired renal function (creatinine &gt;1.5 times upper limit of normal)&#xD;
&#xD;
         12. Has chronic liver function impairment (aspartate aminotransferase or alanine&#xD;
             aminotransferase &gt;3 times upper limit of normal)&#xD;
&#xD;
         13. Has insulin-dependent diabetes or uncontrolled diabetes mellitus (glycosylated&#xD;
             hemoglobin &gt;7%)&#xD;
&#xD;
         14. Has leukopenia (&lt;3500 leukocytes/μL)&#xD;
&#xD;
         15. Has current treatment with any of the following medications:&#xD;
&#xD;
               1. Systemic corticosteroids within 1 month of the planned surgery&#xD;
                  (intranasal/inhaled steroids are acceptable)&#xD;
&#xD;
               2. Immunosuppressant therapy to treat autoimmune diseases (e.g., rheumatoid&#xD;
                  arthritis, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus,&#xD;
                  sarcoidosis, focal segmental glomerulosclerosis, Crohn's disease, Behcet's&#xD;
                  disease, pemphigus, or ulcerative colitis)&#xD;
&#xD;
               3. Oral or topical products containing clonidine (e.g., Catapres®)&#xD;
&#xD;
               4. Antiepileptic drugs, antipsychotics, monoamine oxidase inhibitors, lithium, or&#xD;
                  sulfonamides&#xD;
&#xD;
               5. Calcium channel blocker, digoxin, or beta-adrenergic blockers&#xD;
&#xD;
         16. Chronically uses opioids, defined as use on at least 20 of the last 30 days before&#xD;
             study Screening, and is unable to refrain from opioid use within the 24 hour period&#xD;
             before surgery&#xD;
&#xD;
         17. Investigator determines subject has a known or suspected history of drug or alcohol&#xD;
             abuse&#xD;
&#xD;
         18. Recent dose adjustment or commencement of treatment with selective serotonin reuptake&#xD;
             inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and/or&#xD;
             tricyclic antidepressants (use of these medications is allowed if the dose is stable&#xD;
             for at least 8 weeks before receiving study treatment)&#xD;
&#xD;
         19. Has received any other investigational drug or device within 30 days of Screening&#xD;
&#xD;
         20. Experiences any surgical complication that, in the investigator's opinion, precludes&#xD;
             implantation of MDT-10013.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Achieve Clinical Research, LLC</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Research Associates, LLC</name>
      <address>
        <city>Deland</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Department, University of Orthopedics Center</name>
      <address>
        <city>Altoona</city>
        <state>Pennsylvania</state>
        <zip>16602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2016</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>June 6, 2016</last_update_submitted>
  <last_update_submitted_qc>June 6, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 7, 2016</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 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/NCT02263222
org study id: P13-02
nct id: NCT02263222
lead sponsor: 
has dmc: Yes
This is an open-label dose-escalating study to evaluate the tolerability and systemic
      exposure of MDT-10013 in men and women at least 18 years of age who are undergoing primary
      unilateral TKA.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetic (PK) parameters of MDT-10013--maximum plasma concentration observed (Cmax)
time frame: From day 1 to day 14
measure: Pharmacokinetic (PK) parameters of MDT-10013--time to maximum plasma concentration observed (tmax)
time frame: From day 1 to day 14
measure: Pharmacokinetic (PK) parameters of MDT-10013--area under the plasma concentration versus time curve (AUC)
time frame: From day 1 to day 14
measure: Rate of study drug/treatment-related serious adverse events (SAEs)
time frame: up to 3 months
measure: Summed pain intensity scores at rest
time frame: up to 120 hours
description: Summed pain intensity scores (calculated as a time-weighted average) by using an 11-point (0 to 10) numerical rating scale (NRS).
measure: Summed pain intensity scores over 2 to 48 hours (SPI-48) with activity
time frame: up to 48 hours
measure: Aggregate dosage of all opioid analgesia
time frame: 0 to 24 hours and 0 to 48 hours
measure: Total use of opioid analgesia
time frame: From 48 hours through Day 6/120 hours
measure: Time to first use of opioid analgesia defined as the time from Time 0 to the first use of opioid analgesia.
time frame: Time 0 is defined as the initiation of arthrotomy closure to the first opioid analgesia use
measure: Subject global evaluation of study treatment
time frame: up to 10-14 days
arm group label: MDT-10013
arm group type: Experimental
description: Subjects will receive MDT-10013.
intervention type: Drug
intervention name: MDT-10013
arm group label: MDT-10013
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative