<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/NCT03009045</url>
  </required_header>
  <id_info>
    <org_study_id>21814-01</org_study_id>
    <nct_id>NCT03009045</nct_id>
  </id_info>
  <brief_title>Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint Infections</brief_title>
  <official_title>Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint Infections</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The problem of interest is that doctors are looking for new antibiotic treatments for bone&#xD;
      and joint infections. Treatment for bone and joint infection is not standardized, which&#xD;
      allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called&#xD;
      S. aureus is the most common cause of bone and joint infection. Methicillin resistant S.&#xD;
      aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is&#xD;
      increasingly common in U.S. and non-U.S. medical centers. This problem will be studied by&#xD;
      investigating whether an antibiotic called tedizolid is tolerable, safe and effective to&#xD;
      treat bone and joint infections.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The problem of interest is that doctors are looking for new antibiotic treatments for bone&#xD;
      and joint infections. Treatment for bone and joint infection is not standardized, which&#xD;
      allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called&#xD;
      S. aureus is the most common cause of bone and joint infection. Methicillin resistant S.&#xD;
      aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is&#xD;
      increasingly common in U.S. and non-U.S. medical centers. Trauma-associated bone and joint&#xD;
      infection is also a common problem. Victims of major trauma often suffer bone fractures,&#xD;
      which require temporary or permanent use of metal or other synthetic devices such as&#xD;
      external-fixation pins, plates, and screws. These synthetic devices can also get infected and&#xD;
      cause bone and joint infections.&#xD;
&#xD;
      This problem will be studied by investigating whether an antibiotic called tedizolid is&#xD;
      tolerable, safe and effective to treat bone and joint infections. Tedizolid is a new&#xD;
      FDA-approved antibiotic, and can be given through the bloodstream via an IV or orally in the&#xD;
      form of a pill. Tedizolid has less side effects compared to linezolid and is effective&#xD;
      against types of bacteria like S. aureus. Other research also suggests that the side effects&#xD;
      associated with long-term therapy of older types of antibiotics may not be found with&#xD;
      tedizolid.&#xD;
&#xD;
      This study will advance scientific knowledge of antibiotic treatments for bone and joint&#xD;
      infections. Given the large and increasing burden of disease of bone and joint infection and&#xD;
      the increasing acceptability of oral antibiotics for its management, tedizolid holds promise&#xD;
      as a good option for patients with bone and joint infection. Harbor-UCLA Medical Center is a&#xD;
      large medical center in the County of Los Angeles, the most populous County in the United&#xD;
      States. The Infectious Disease consult service sees many bone and joint infections. Use of&#xD;
      prolonged antibiotics is common in this setting. The investigators believe tedizolid&#xD;
      addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for&#xD;
      use as a prolonged therapy for bone and joint infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 6, 2017</start_date>
  <completion_date type="Anticipated">January 2022</completion_date>
  <primary_completion_date type="Anticipated">July 2021</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>Number of &quot;moderate&quot; or &quot;serious&quot; adverse events as assessed by MedDRA v18.1</measure>
    <time_frame>4-12 Weeks</time_frame>
    <description>Study Hypothesis: Tedizolid is well tolerated for prolonged (4-12 weeks)courses of antibiotic therapy for patients with bone and joint infection. Comprehensive Chemistry Panels including liver function tests (CMP) and Complete Blood Count (CBC) Panels will be collected at regular intervals along with standardized surveys to measure adverse events as defined by the Medical Dictionary for Regulatory Activities Terminology (MedDRA) Version 18.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with an outcome of &quot;cure&quot; as defined as no need for further antibiotics beyond the originally planned duration determined by the participant's primary/treating physician.</measure>
    <time_frame>4-12 Weeks</time_frame>
    <description>Study Hypothesis: Tedizolid is effective for the treatment of bone and joint infection. Specifically, cure will be defined as no need for further antibiotics beyond the originally planned duration (i.e., 6 weeks for non-device associated bone and joint infection or until hardware removal for subjects with implants). Unplanned surgical procedures prompted by inadequate infection control will be categorized as treatment failure. We will also measure long-term efficacy by performing a phone survey 3 months after completion of antibiotics. Recurrence of signs or symptoms of bone and joint infection will be considered a long-term treatment failure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by MedDRA v18.1</measure>
    <time_frame>4-12 weeks</time_frame>
    <description>Study Hypothesis: Tedizolid is safe for prolonged (4-12 weeks) courses of antibiotic therapy for patients with bone and joint infection. Comprehensive Chemistry Panels including liver function tests (CMP) and Complete Blood Count (CBC) Panels will be collected at regular intervals along with standardized surveys to measure adverse events as defined by the Medical Dictionary for Regulatory Activities Terminology (MedDRA) Version 18.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Bone and Joint Infection</condition>
  <arm_group>
    <arm_group_label>Drug: 200mg oral Tedizolid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200mg oral tablet of tedizolid to be taken once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tedizolid</intervention_name>
    <description>200mg oral tedizolid one pill per day</description>
    <arm_group_label>Drug: 200mg oral Tedizolid</arm_group_label>
    <other_name>tedizolid phosphate</other_name>
    <other_name>Sivextro</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Treatment of bone and joint infection in which therapy for Gram positive organisms is&#xD;
             documented or suspected, as determined by the treating physician and treatment of at&#xD;
             least 4 weeks is planned. Bone and joint infection and trauma-associated bone and&#xD;
             joint infection will defined clinically using radiologic (e.g., MRI) and/or surgical&#xD;
             (e.g., intra-operative findings)&#xD;
&#xD;
          -  Aged between 18 years and 85 years.&#xD;
&#xD;
          -  Plans to treat bone and joint infection in outpatient setting.&#xD;
&#xD;
          -  No limited planned course of antibiotics (i.e., no indefinite treatment plans for&#xD;
             chronic suppression). Co-administration of other antibiotics that target other&#xD;
             causative or potentially causative organisms (e.g., fluoroquinolones) is acceptable.&#xD;
&#xD;
          -  Able to come to the research clinic for study follow-up visits for the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Planned prolonged hospitalization (&gt; 1 week).&#xD;
&#xD;
          -  Pregnancy (all female subjects of childbearing age will be given a pregnancy test&#xD;
             prior to enrollment) or breast feeding. If a women is of childbearing potential, she&#xD;
             must consistently use an acceptable method of contraception (IUD, injectable&#xD;
             contraceptive, birth control patch, OCP, barrier method, abstinence) from baseline&#xD;
             through the course of antibiotics (4-12 weeks). If a male patient's sexual partner is&#xD;
             of childbearing potential, the male patient must acknowledge that they will&#xD;
             consistently use an acceptable method of contraception as defined above from baseline&#xD;
             through the course of antibiotics (4-12 weeks).&#xD;
&#xD;
          -  Comorbidities that, in the opinion of the investigator, are uncontrolled (e.g.,&#xD;
             diabetes, hypertension, psychiatric disease).&#xD;
&#xD;
          -  Peripheral or optic neuropathy.&#xD;
&#xD;
          -  Underlying hematologic cytopenias (e.g., baseline thrombocytopenia, or severe anemia,&#xD;
             or leukopenia) as determined by the following limits from a baseline CBC/CMP obtained&#xD;
             within the past 14 days. Note that if a CBC has not been performed within the past 14&#xD;
             days, a CBC will be performed on the day of enrollment prior to any study drug being&#xD;
             administered to ensure the patient does not meet exclusion criteria. Cytopenias are&#xD;
             defined as:&#xD;
&#xD;
               1. Hemoglobin (Hgb) &lt; 8.0g/dL&#xD;
&#xD;
               2. WBC &lt; 4,000 k/cumm&#xD;
&#xD;
               3. Platelets &lt; 150,000 k/cumm&#xD;
&#xD;
          -  Severe hepatic dysfunction as defined by liver function tests (ALT, ALP, AST, total&#xD;
             bilirubin) &gt; 3.0 times the upper limit of normal. as determined by the following&#xD;
             limits from a baseline CMP obtained within the past 7 days. If a CMP has not been&#xD;
             performed within the past 7 days, baseline levels may be used from a CMP performed&#xD;
             within the past 2 months as long as another CMP is performed on the day of enrollment&#xD;
             and the subject's levels are within the following limits.&#xD;
&#xD;
          -  Hypersensitivity to tedizolid or other oxazolidinone-class antibiotics or similar&#xD;
             compounds.&#xD;
&#xD;
          -  Ongoing antibiotic-associated colitis.&#xD;
&#xD;
          -  A diet high in tyramine-containing foods such as pickled or fermented meats and&#xD;
             cheeses, wine, or avocados per investigator discretion.&#xD;
&#xD;
          -  Concurrent use of sodium picosulfate (brand names: Sodipic Picofast, Laxoberal,&#xD;
             Laxoberon, Purg-Odan, Picolax, Guttalax, Namilax, Pico-Salax and Prepopik).&#xD;
&#xD;
          -  Previous participation in the study.&#xD;
&#xD;
          -  Use of tedizolid for any condition in the past 3 months.&#xD;
&#xD;
          -  Any other medical, psychological, or social condition that, in the opinion of the&#xD;
             Investigator, would prevent the patient from fully participating in the study or would&#xD;
             represent a concern for study compliance or constitute a safety concern to the&#xD;
             patient.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Loren G Miller, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Harbor-UCLA Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Los Angeles BioMedical Research Institute (LA BioMed)</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <last_update_submitted>February 22, 2021</last_update_submitted>
  <last_update_submitted_qc>February 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center</investigator_affiliation>
    <investigator_full_name>loren g miller</investigator_full_name>
    <investigator_title>Primary Investigator, Associate Chief of Division of Infectious Diseases</investigator_title>
  </responsible_party>
  <keyword>bone and joint infection</keyword>
  <keyword>osteomyelitis</keyword>
  <keyword>tedizolid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Arthritis, Infectious</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tedizolid</mesh_term>
    <mesh_term>Tedizolid phosphate</mesh_term>
    <mesh_term>Oxazolidinones</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>After publication of trial results, data will be shared with investigators upon request to the Principal Investigator and after signing a Data Use Agreement.</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>March 1, 2023</submitted>
    <returned>March 28, 2023</returned>
    <submitted>August 29, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03009045
org study id: 21814-01
nct id: NCT03009045
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The problem of interest is that doctors are looking for new antibiotic treatments for bone
      and joint infections. Treatment for bone and joint infection is not standardized, which
      allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called
      S. aureus is the most common cause of bone and joint infection. Methicillin resistant S.
      aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is
      increasingly common in U.S. and non-U.S. medical centers. This problem will be studied by
      investigating whether an antibiotic called tedizolid is tolerable, safe and effective to
      treat bone and joint infections.
The problem of interest is that doctors are looking for new antibiotic treatments for bone
      and joint infections. Treatment for bone and joint infection is not standardized, which
      allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called
      S. aureus is the most common cause of bone and joint infection. Methicillin resistant S.
      aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is
      increasingly common in U.S. and non-U.S. medical centers. Trauma-associated bone and joint
      infection is also a common problem. Victims of major trauma often suffer bone fractures,
      which require temporary or permanent use of metal or other synthetic devices such as
      external-fixation pins, plates, and screws. These synthetic devices can also get infected and
      cause bone and joint infections.

      This problem will be studied by investigating whether an antibiotic called tedizolid is
      tolerable, safe and effective to treat bone and joint infections. Tedizolid is a new
      FDA-approved antibiotic, and can be given through the bloodstream via an IV or orally in the
      form of a pill. Tedizolid has less side effects compared to linezolid and is effective
      against types of bacteria like S. aureus. Other research also suggests that the side effects
      associated with long-term therapy of older types of antibiotics may not be found with
      tedizolid.

      This study will advance scientific knowledge of antibiotic treatments for bone and joint
      infections. Given the large and increasing burden of disease of bone and joint infection and
      the increasing acceptability of oral antibiotics for its management, tedizolid holds promise
      as a good option for patients with bone and joint infection. Harbor-UCLA Medical Center is a
      large medical center in the County of Los Angeles, the most populous County in the United
      States. The Infectious Disease consult service sees many bone and joint infections. Use of
      prolonged antibiotics is common in this setting. The investigators believe tedizolid
      addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for
      use as a prolonged therapy for bone and joint infection.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of "moderate" or "serious" adverse events as assessed by MedDRA v18.1
time frame: 4-12 Weeks
description: Study Hypothesis: Tedizolid is well tolerated for prolonged (4-12 weeks)courses of antibiotic therapy for patients with bone and joint infection. Comprehensive Chemistry Panels including liver function tests (CMP) and Complete Blood Count (CBC) Panels will be collected at regular intervals along with standardized surveys to measure adverse events as defined by the Medical Dictionary for Regulatory Activities Terminology (MedDRA) Version 18.1
measure: Number of participants with an outcome of "cure" as defined as no need for further antibiotics beyond the originally planned duration determined by the participant's primary/treating physician.
time frame: 4-12 Weeks
description: Study Hypothesis: Tedizolid is effective for the treatment of bone and joint infection. Specifically, cure will be defined as no need for further antibiotics beyond the originally planned duration (i.e., 6 weeks for non-device associated bone and joint infection or until hardware removal for subjects with implants). Unplanned surgical procedures prompted by inadequate infection control will be categorized as treatment failure. We will also measure long-term efficacy by performing a phone survey 3 months after completion of antibiotics. Recurrence of signs or symptoms of bone and joint infection will be considered a long-term treatment failure.
measure: Number of participants with treatment-related adverse events as assessed by MedDRA v18.1
time frame: 4-12 weeks
description: Study Hypothesis: Tedizolid is safe for prolonged (4-12 weeks) courses of antibiotic therapy for patients with bone and joint infection. Comprehensive Chemistry Panels including liver function tests (CMP) and Complete Blood Count (CBC) Panels will be collected at regular intervals along with standardized surveys to measure adverse events as defined by the Medical Dictionary for Regulatory Activities Terminology (MedDRA) Version 18.1
arm group label: Drug: 200mg oral Tedizolid
arm group type: Experimental
description: 200mg oral tablet of tedizolid to be taken once daily
intervention type: Drug
intervention name: Tedizolid
description: 200mg oral tedizolid one pill per day
arm group label: Drug: 200mg oral Tedizolid
other name: tedizolid phosphate
other name: Sivextro
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Loren G Miller, MD MPH
role: Principal Investigator
affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
investigator full name: loren g miller
investigator title: Primary Investigator, Associate Chief of Division of Infectious Diseases
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Arthritis, Infectious
mesh term: Tedizolid
mesh term: Tedizolid phosphate
mesh term: Oxazolidinones
sharing ipd: Yes
ipd description: After publication of trial results, data will be shared with investigators upon request to the Principal Investigator and after signing a Data Use Agreement.
submitted: March 1, 2023
returned: March 28, 2023
submitted: August 29, 2023