xml: <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/NCT06020235</url>
    </required_header>
    <id_info>
      <org_study_id>LAI-Nu-3-CLIN004</org_study_id>
      <nct_id>NCT06020235</nct_id>
    </id_info>
    <brief_title>Nu-3 Gel for Infected Diabetic Foot Ulcers</brief_title>
    <official_title>A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Antimicrobial Efficacy Of Topically Once Or Twice Daily Applied Bisphosphocin® Nu-3 Gel At 5% And 10% Concentrations To Infected Diabetic Foot Ulcers (iDFU)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Lakewood-Amedex Inc</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Lakewood-Amedex Inc</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to test a topical drug in patients with mild infections of&#xD;
        their diabetic foot ulcer. The main questions it aims to answer are:&#xD;
  &#xD;
        What strength does the drug need to be in order to make the infection better? How frequently&#xD;
        does the drug need to be applied in order to make the infection better? Participants will be&#xD;
        asked to apply the medicine on their foot ulcer twice a day for 2 weeks and remain off of&#xD;
        that foot during that time.&#xD;
  &#xD;
        Participants will receive the medication either once a day or twice a day, in either a 5% or&#xD;
        10% gel, or placebo.&#xD;
  &#xD;
        Researchers will compare the 5% and 10% gels to placebo to see if the infection improves.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">July 2024</completion_date>
    <primary_completion_date type="Anticipated">May 2024</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>Safety</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>Number of AEs overall and those assessed by the investigators as possibly, probably, and definitely related to the study drug; number of SAEs per patient and cohort</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Efficacy</measure>
      <time_frame>Day 0 to Day 14</time_frame>
      <description>The rate of reduction in CFUs by &gt;=2 logs per pathogen identified as typical and highly suspicious for being the cause of the infection, in each treatment group compared to placebo group at Day 7 compared to Day 0, and Day 14 compared to Day 0.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Treatment failure rate per treatment regimen</measure>
      <time_frame>Day 0 to Day 14</time_frame>
      <description>The proportion of patients whose infection was not cured, defined as resolution of all wound infection signs, or whose infection did not improve over the course of the study defined as a lower number of clinical signs of infection or lower extent or severity as assesed by wound infection score.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Treatment failure rate per treatment regimen</measure>
      <time_frame>Day 0 to Day 14</time_frame>
      <description>Number of treatment failures, defined as need to switch to oral antibiotic treatment based on clinical wound-infection assessment by the PI, per cohort</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>Number of AEs (overall and those assessed by the investigators as possibly, probably and definitely related to the study drug) and SAEs per patient and cohort and clinically relevant changes in physical examination, vital signs, laboratory and/or ECG measurements at the defined timepoints compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>Change in parameters indicative of skin irritation and/or skin sensitization compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics</measure>
      <time_frame>Day 0 to Day 13</time_frame>
      <description>Maximum concentration in the first 20 patients sampled for PK across all dosing groups after initial and repeated dosing</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Wound healing</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>Percentage area reduction of wound size at Day 7, Day 14, and Day 28 compared to baseline</description>
    </other_outcome>
    <other_outcome>
      <measure>Wound healing</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>Change in the 5-component clinical signs DFI score at all timepoints compared to baseline</description>
    </other_outcome>
    <other_outcome>
      <measure>Wound healing</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>Change in the overall DFI score at all timepoints compared to baseline</description>
    </other_outcome>
    <number_of_arms>5</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Diabetic Foot Infection</condition>
    <arm_group>
      <arm_group_label>5% Nu-3 gel once daily</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The 5% Nu-3 gel is applied once per day and placebo is applied once per day.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>5% Nu-3 gel twice daily</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The 5% Nu-3 gel is applied twice per day.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>10% Nu-3 gel once daily</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The 10% Nu-3 gel is applied once per day and placebo is applied once per day.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>10% Nu-3 gel twice daily</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The 10% Nu-3 gel is applied twice per day.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>The placebo is applied twice per day.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>5% Nu-3 gel</intervention_name>
      <description>The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.</description>
      <arm_group_label>5% Nu-3 gel once daily</arm_group_label>
      <arm_group_label>5% Nu-3 gel twice daily</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>10% Nu-3 gel</intervention_name>
      <description>The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.</description>
      <arm_group_label>10% Nu-3 gel once daily</arm_group_label>
      <arm_group_label>10% Nu-3 gel twice daily</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo gel is either applied once per day or twice per day to the infected ulcer.</description>
      <arm_group_label>10% Nu-3 gel once daily</arm_group_label>
      <arm_group_label>5% Nu-3 gel once daily</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1. Male and female subjects ≥18 years of age. 2. Voluntary written informed consent,&#xD;
               including information about the provisions of the Health Insurance Portability and&#xD;
               accountability act (HIPAA) as applicable.&#xD;
  &#xD;
               3. Non-hospitalized ambulatory subjects diagnosed with diabetes mellitus, Type I or II&#xD;
               per ADA criteria with signs of a localized mild foot infection as defined by the IDSA&#xD;
               infection severity criteria (Lipsky,2012)&#xD;
  &#xD;
               a. the presence of purulent drainage or at least two of the following criteria: i.&#xD;
               erythema, ii. warmth, iii. pain or tenderness, iv. edema, or v. induration (The&#xD;
               diagnosis of mild infection must be confirmed immediately following debridement at&#xD;
               Baseline).&#xD;
  &#xD;
               4. The target ulcer is classified as a grade 1 ulcer according to the Wagner Scale&#xD;
               (Wagner 1979). The ulcer is a superficial, full-thickness ulcer limited to the dermis,&#xD;
               not extending to the subcutis. Target ulcer is &gt;1 cm2 and &lt;12 cm2 post debridement at&#xD;
               baseline and must be no higher than the ankle, on or below the malleolus (ankle bone)&#xD;
               with ≥50% below the malleolus.&#xD;
  &#xD;
               5. Adequate vascular perfusion as evidenced by one of the following:&#xD;
  &#xD;
                 1. Dorsal transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure&#xD;
                    (SPP) measurement of ≥ 40 mmHg&#xD;
  &#xD;
                 2. Ankle Branchial Index (ABI) between 0.9 and 1.3 within 3 months of Screening&#xD;
                    using the extremity with the target ulcer.&#xD;
  &#xD;
                 3. Arterial Doppler ultrasound evaluating for biphasic or triphasic dorsalis pedis&#xD;
                    and posterior tibial vessels at the level of the ankle or a TBI (Toe Brachial&#xD;
                    Index) of &gt;0.75.&#xD;
  &#xD;
                    6. Subject has a caregiver who will attend the Baseline visit (V2) and/or watch&#xD;
                    the dosing and dressing demonstration video and apply wound treatment along with&#xD;
                    study dressings for the study duration.&#xD;
  &#xD;
                    7. Must meet one of the following criteria:&#xD;
  &#xD;
               a. Female subjects of Non-Child-Bearing Potential i. Postmenopausal for at least 1&#xD;
               year ii. Surgically sterilized (i.e., hysterectomy or bilateral oophorectomy more than&#xD;
               3 months prior to Screening) iii. Bilateral tube ligation &gt; 6 months prior to&#xD;
               screening iv. A negative serum β-hCG pregnancy test at screening and no breastfeeding&#xD;
               after the administration of the study drug.&#xD;
  &#xD;
               b. Male subjects of Non-Childbearing Potential defined as: i. Vasectomized subjects&#xD;
               for &gt; 6 months prior to Screening ii. Those diagnosed as sterile by a physician. c.&#xD;
               Females and Males of Childbearing Potential who practice an acceptable method of&#xD;
               contraception defined as the i. Use of any form of hormonal contraceptive ii. Use of a&#xD;
               barrier method with spermicide, condoms, intrauterine device, iii. Abstinence from&#xD;
               sexual intercourse starting at least 60 days prior to Screening and continuing at&#xD;
               least 14 days following the last treatment.&#xD;
  &#xD;
               8. Subjects must be willing to undergo all clinical investigation-related procedures,&#xD;
               attend all required visits, and cooperate fully with the investigator and site&#xD;
               personnel.&#xD;
  &#xD;
               9. Subject must be willing to wear offloading RCW, if necessary, throughout the&#xD;
               duration of the clinical treatment.&#xD;
  &#xD;
               10. Subject must have plain radiograph taken at screening and prior to randomization&#xD;
               showing no evidence of bony abnormalities consistent with osteomyelitis, or gas&#xD;
               compatible with tissue crepitus, in the affected foot.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1. Ulceration with exposed tendon, capsule, or bone 2. IDSA-defined moderate or severe&#xD;
               DFU infection. 3. Infected diabetic foot ulcer that is associated with local wound&#xD;
               complication such as prosthetic materials or protruding surgical hardware.&#xD;
  &#xD;
               4. &gt; 1 infected foot ulcer 5. Subject is currently receiving topical antimicrobial&#xD;
               treatment for a localized infection of the study ulcer and whose infection is&#xD;
               improving in response to treatment.&#xD;
  &#xD;
               6. Subject has received a systemic antibiotic within 48 hours prior to Screening.&#xD;
  &#xD;
               7. Concurrent or expected to require systemic antimicrobials during the study period&#xD;
               for any infection including diabetic foot ulcer.&#xD;
  &#xD;
               8. Any subject that has active viral hepatitis (A, B, C) and/or untreated HIV/AIDS.&#xD;
  &#xD;
               9. Any subject that has vascular compromise requiring surgical intervention or has&#xD;
               undergone vascular reconstruction or angioplasty less than 1 month prior to&#xD;
               randomization. Any planned surgical procedures during the study participation 10. eGFR&#xD;
               &lt;60 and/or subject on hemodialysis within 3 months prior to randomization.&#xD;
  &#xD;
               11. Hemoglobin A1c (HbA1c) &gt;12% within 3 months prior to randomization. 12. Aspartate&#xD;
               Aminotransferase (AST, GOT) and/or Alanine Aminotransferase (ALT, GPT) &gt;3.0 x the&#xD;
               upper limit of normal and/or bilirubin &gt;1.5 x the upper limit of normal within 3&#xD;
               months prior to randomization.&#xD;
  &#xD;
               13. Acute active Charcot foot 14. Any subject that would be unable to safely monitor&#xD;
               the infection status at home and return for scheduled visits.&#xD;
  &#xD;
               15. History of immunosuppression within 3 months prior to randomization, or taking&#xD;
               immunosuppressive agents including systemic corticosteroids, except stable daily doses&#xD;
               of 5 mg/day or less for chronic conditions 16. Any subject with a life expectancy ≤ 6&#xD;
               months 17. Use of investigational drugs within 28 days prior to screening 18. Use of&#xD;
               Aspirin® or acetylsalicylic acid containing medication (except low-dose aspirin) &lt; 7&#xD;
               days before baseline, 19. Use of oral anticoagulants (e.g., warfarin, Xarelto® or&#xD;
               comparable products).&#xD;
  &#xD;
               20. History of concurrent condition that, in the Investigator's opinion, would&#xD;
               jeopardize the safety of the subject or compliance with the protocol including known&#xD;
               or suspected active abuse of alcohol, narcotics, or non-prescription drugs.&#xD;
  &#xD;
               21. Prior randomization in this clinical trial, or a previous Bisphosphocin study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Thomas Balzer</last_name>
      <phone>941-225-2516</phone>
      <phone_ext>108</phone_ext>
      <email>tbalzer@lakewoodamedex.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 27, 2023</last_update_submitted>
    <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</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>Diabetic Foot</mesh_term>
      <mesh_term>Foot Ulcer</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06020235
  org study id: LAI-Nu-3-CLIN004
  nct id: NCT06020235
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The goal of this clinical trial is to test a topical drug in patients with mild infections of
        their diabetic foot ulcer. The main questions it aims to answer are:
  
        What strength does the drug need to be in order to make the infection better? How frequently
        does the drug need to be applied in order to make the infection better? Participants will be
        asked to apply the medicine on their foot ulcer twice a day for 2 weeks and remain off of
        that foot during that time.
  
        Participants will receive the medication either once a day or twice a day, in either a 5% or
        10% gel, or placebo.
  
        Researchers will compare the 5% and 10% gels to placebo to see if the infection improves.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Safety
  time frame: Day 0 to Day 28
  description: Number of AEs overall and those assessed by the investigators as possibly, probably, and definitely related to the study drug; number of SAEs per patient and cohort
  measure: Efficacy
  time frame: Day 0 to Day 14
  description: The rate of reduction in CFUs by >=2 logs per pathogen identified as typical and highly suspicious for being the cause of the infection, in each treatment group compared to placebo group at Day 7 compared to Day 0, and Day 14 compared to Day 0.
  measure: Treatment failure rate per treatment regimen
  time frame: Day 0 to Day 14
  description: The proportion of patients whose infection was not cured, defined as resolution of all wound infection signs, or whose infection did not improve over the course of the study defined as a lower number of clinical signs of infection or lower extent or severity as assesed by wound infection score.
  measure: Treatment failure rate per treatment regimen
  time frame: Day 0 to Day 14
  description: Number of treatment failures, defined as need to switch to oral antibiotic treatment based on clinical wound-infection assessment by the PI, per cohort
  measure: Safety
  time frame: Day 0 to Day 28
  description: Number of AEs (overall and those assessed by the investigators as possibly, probably and definitely related to the study drug) and SAEs per patient and cohort and clinically relevant changes in physical examination, vital signs, laboratory and/or ECG measurements at the defined timepoints compared to baseline
  measure: Safety
  time frame: Day 0 to Day 28
  description: Change in parameters indicative of skin irritation and/or skin sensitization compared to baseline
  measure: Pharmacokinetics
  time frame: Day 0 to Day 13
  description: Maximum concentration in the first 20 patients sampled for PK across all dosing groups after initial and repeated dosing
  measure: Wound healing
  time frame: Day 0 to Day 28
  description: Percentage area reduction of wound size at Day 7, Day 14, and Day 28 compared to baseline
  measure: Wound healing
  time frame: Day 0 to Day 28
  description: Change in the 5-component clinical signs DFI score at all timepoints compared to baseline
  measure: Wound healing
  time frame: Day 0 to Day 28
  description: Change in the overall DFI score at all timepoints compared to baseline
  arm group label: 5% Nu-3 gel once daily
  arm group type: Experimental
  description: The 5% Nu-3 gel is applied once per day and placebo is applied once per day.
  arm group label: 5% Nu-3 gel twice daily
  arm group type: Experimental
  description: The 5% Nu-3 gel is applied twice per day.
  arm group label: 10% Nu-3 gel once daily
  arm group type: Experimental
  description: The 10% Nu-3 gel is applied once per day and placebo is applied once per day.
  arm group label: 10% Nu-3 gel twice daily
  arm group type: Experimental
  description: The 10% Nu-3 gel is applied twice per day.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: The placebo is applied twice per day.
  intervention type: Drug
  intervention name: 5% Nu-3 gel
  description: The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.
  arm group label: 5% Nu-3 gel once daily
  arm group label: 5% Nu-3 gel twice daily
  intervention type: Drug
  intervention name: 10% Nu-3 gel
  description: The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.
  arm group label: 10% Nu-3 gel once daily
  arm group label: 10% Nu-3 gel twice daily
  intervention type: Drug
  intervention name: Placebo
  description: Placebo gel is either applied once per day or twice per day to the infected ulcer.
  arm group label: 10% Nu-3 gel once daily
  arm group label: 5% Nu-3 gel once daily
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Thomas Balzer
  phone: 941-225-2516
  phone ext: 108
  email: tbalzer@lakewoodamedex.com
  responsible party type: Sponsor
  mesh term: Diabetic Foot
  mesh term: Foot Ulcer
  sharing ipd: No