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/NCT05968482</url>
    </required_header>
    <id_info>
      <org_study_id>AMZ001-008</org_study_id>
      <nct_id>NCT05968482</nct_id>
    </id_info>
    <brief_title>Bioavailability and Safety Study Comparing Two Dose Levels of AMZ001 and One Dose Level of Diclofenac Sodium 1% Gel in Healthy Participants</brief_title>
    <official_title>A Phase 1, Single-Center, Randomized, Open-Label, Bioavailability and Safety Three Period Crossover Multiple-Dose Study Comparing Two Dose Levels of AMZ001 (Diclofenac Sodium Gel 3.06%) and One Dose Level of Diclofenac Sodium 1% Gel in Healthy Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Amzell</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Amzell</source>
    <oversight_info>
      <has_dmc>No</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 goal of this clinical trial is to compare drug exposure from two different products&#xD;
        (AMZ001 and Diclofenac Sodium 1% Gel) in healthy participants on Day 7 after repeated topical&#xD;
        administrations for 7 days.&#xD;
  &#xD;
        Participants will receive, in a crossover design, three different treatments&#xD;
  &#xD;
          -  AMZ001 Low dose&#xD;
  &#xD;
          -  AMZ001 High dose&#xD;
  &#xD;
          -  Diclofenac Sodium 1% Gel&#xD;
  &#xD;
        Safety and tolerability of AMZ001 will be also investigated.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        On their both knees, participants will apply once daily either low dose of AMZ001 or high&#xD;
        dose of AMZ001 for 7 consecutive days. Participants will also apply Diclofenac Sodium 1% Gel&#xD;
        as per label information on each knee.&#xD;
  &#xD;
        Intensive pharmacokinetic assessment (blood samplings) will be performed on the first day of&#xD;
        application (Day 1) as well as on the last day of application (Day 7).&#xD;
  &#xD;
        Each participant will receive each of the three treatments in a randomized manner. Between&#xD;
        each treatment, participant will not receive any of the three tested therapies between 3&#xD;
        weeks before receiving the next therapy. (washout period)&#xD;
  &#xD;
        Participants will stay on the clinical unit only during each period of treatment but not&#xD;
        during washout period.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 11, 2023</start_date>
    <completion_date type="Anticipated">May 17, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 26, 2023</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Compare exposure to diclofenac</measure>
      <time_frame>Day 7</time_frame>
      <description>Area under the curve from time zero to 24 hours and maximum (peak) plasma drug concentration</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic parameter - Cmin</measure>
      <time_frame>Day 7</time_frame>
      <description>Minimum plasma drug concentration (Cmin)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic parameter - Tmax</measure>
      <time_frame>Day 7</time_frame>
      <description>Time to reach maximum plasma concentration (Tmax)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic parameter - Ke</measure>
      <time_frame>Day 7</time_frame>
      <description>Terminal disposition rate constant (Ke)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic parameter - Cavg</measure>
      <time_frame>Day 7</time_frame>
      <description>Average plasma concentration (Cavg)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic parameter - Cmax</measure>
      <time_frame>Day 1</time_frame>
      <description>Maximum plasma drug concentration (Cmax)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic parameter - Tmax</measure>
      <time_frame>Day 1</time_frame>
      <description>Time to reach maximum plasma concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic parameter - Cavg</measure>
      <time_frame>Day 1</time_frame>
      <description>Average plasma concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Local tolerability</measure>
      <time_frame>Day 1 to Day 7</time_frame>
      <description>Incidence of application site reactions according to the terminology of the International Contact Dermatitis Research Group</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">75</enrollment>
    <condition>Healthy</condition>
    <arm_group>
      <arm_group_label>AMZ001 Low dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>AMZ001 applied once daily for 7 consecutive days</description>
    </arm_group>
    <arm_group>
      <arm_group_label>AMZ001 High dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>AMZ001 applied once daily for 7 consecutive days</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Diclofenac Sodium 1% Gel</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Reference product applied four-times daily for 7 consecutive days</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Diclofenac Sodium Gel</intervention_name>
      <description>Topical application on both knees</description>
      <arm_group_label>AMZ001 High dose</arm_group_label>
      <arm_group_label>AMZ001 Low dose</arm_group_label>
      <arm_group_label>Diclofenac Sodium 1% Gel</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Healthy male or female participants 18-65 years of age (e.g., in general good physical&#xD;
               health, as judged by the Investigator and no clinically relevant abnormalities&#xD;
               identified by a detailed medical history, full physical examination, including blood&#xD;
               pressure and pulse rate measurement, 12-lead ECG (electrocardiogram) or clinical&#xD;
               laboratory tests)&#xD;
  &#xD;
            -  Has a body mass index (BMI) between 18.0 and 35.0 kg/m^2 (kilogram per square meter)&#xD;
               at Screening.&#xD;
  &#xD;
            -  In the case of females of child-bearing potential ([FCBP) unless surgically sterilized&#xD;
               [hysterectomy, bilateral oophorectomy, bilateral tubal ligation] or are postmenopausal&#xD;
               for at least 12 months), are using two acceptable forms of birth control (hormonal&#xD;
               contraceptives i.e., oral/implant/injectable/transdermal; intrauterine device (IUD)&#xD;
               and/or barrier methods [female condom, male condom, diaphragm, cervical cap,&#xD;
               spermicide]; note: 2 barrier methods are two acceptable forms of birth control)).&#xD;
               Abstinence or partner's vasectomies are acceptable if the female participant agrees to&#xD;
               implement two acceptable forms of birth control if her lifestyle/partner changes.&#xD;
  &#xD;
            -  Females of child-bearing potential have a negative serum pregnancy test (SPT) at&#xD;
               Screening and negative urine pregnancy test (UPT) on Day -1 of each period and at end&#xD;
               of treatment (EOT) visit&#xD;
  &#xD;
            -  Are free of any systemic or dermatologic disorder and chronic or acute infections,&#xD;
               which, in the opinion of the Principal Investigator (PI), will interfere with the&#xD;
               study results or increase the risk of adverse events (AEs)&#xD;
  &#xD;
            -  Read, understand, and provide signed informed consent before any assessment is&#xD;
               performed.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participant has any visible skin disease, skin lesions, wounds, or a significant&#xD;
               amount of hair at the application site (knee)&#xD;
  &#xD;
            -  Use of an investigational medicinal product (IMP) within 30 days or 5 half-lives (if&#xD;
               known), whichever is longer, of enrollment or during the study.&#xD;
  &#xD;
            -  Treated with systemic or local diclofenac within 30 days of enrollment or during the&#xD;
               study (except for study IMP)&#xD;
  &#xD;
            -  Known hypersensitivity to diclofenac, aspirin, Xarelto, coumadin, or other&#xD;
               non-steroidal anti-inflammatory drugs (NSAIDs), including Cyclooxygenase-2 (COX-2)&#xD;
               inhibitors.&#xD;
  &#xD;
            -  Any history of drug hypersensitivity, asthma, urticaria, or other significant allergic&#xD;
               diathesis. Participants with uncomplicated seasonal allergic rhinitis can be accepted&#xD;
               only if the expected allergy season is clearly outside enrollment / treatment periods.&#xD;
  &#xD;
            -  Females who are pregnant and/or lactating&#xD;
  &#xD;
            -  Of child-bearing potential but not willing to use adequate contraception for the&#xD;
               duration of the study&#xD;
  &#xD;
            -  Participant is a current smoker and unable to abstain from smoking during the&#xD;
               treatment periods.&#xD;
  &#xD;
            -  Use of any topical medication, cosmetics, cream, ointments, lotions on the treatment&#xD;
               site 1 week prior to enrollment through EOT visit&#xD;
  &#xD;
            -  Use of any medication (including over-the-counter medication, dietary supplements, and&#xD;
               herbal remedies) within 2 weeks before first scheduled study drug administration or&#xD;
               within less than 5 times the elimination half-life of the respective drug (whichever&#xD;
               is longer) or is anticipated to require concomitant medication during the 2-week&#xD;
               period or at any time throughout the study. Consumption of any drug metabolizing&#xD;
               enzyme (e.g., cytochrome P450 3A4 (CYP3A4) or other cytochrome P450 enzymes) inducing&#xD;
               or inhibiting beverages or food (e.g., broccoli, Brussel sprouts, grapefruit,&#xD;
               grapefruit juice, star fruit) within 3 days prior to and during each treatment period&#xD;
  &#xD;
            -  Participant has a known or suspected malignancy, excluding basal cell cancer unless it&#xD;
               is associated with the treatment area.&#xD;
  &#xD;
            -  Participant has a positive blood screen for human immunodeficiency virus (HIV),&#xD;
               hepatitis B surface antigen (HBsAg), hepatitis C antibody (Anti-HCV)&#xD;
  &#xD;
            -  Participant has any acute or chronic condition or is using medications, which, in the&#xD;
               investigator's opinion, would make it unsafe for the participant to participate in&#xD;
               this study, including clinically significant abnormal laboratory values, vital signs,&#xD;
               physical examination findings prior to randomization or during study participation.&#xD;
  &#xD;
            -  History or current evidence of renal disease or impaired renal function at screening&#xD;
               as indicated by abnormal levels of serum creatinine (greater than (&gt;) 1.43 mg/dL&#xD;
               (milligram per deciliter)) or blood urea nitrogen (greater than or equal to (≥) 35&#xD;
               mg/dL) or the presence of clinical significant abnormal urinary constituents (e.g.,&#xD;
               albuminuria)&#xD;
  &#xD;
            -  History or current evidence of ongoing hepatic disease or impaired hepatic function at&#xD;
               screening. A participant will be excluded if more than one of the following lab value&#xD;
               deviations are found: 1) aspartate aminotransferase (AST) (≥ 1.5 upper limit of normal&#xD;
               (ULN)), alanine aminotransferase (ALT) (≥ 1.5 ULN), 2) Gamma-Glutamyl Transferase&#xD;
               (GGT) (≥ 1.5 ULN), alkaline phosphatase (ALP) (≥ 1.5 ULN), 3) total bilirubin (&gt; 2.00&#xD;
               mg/dL) or creatine kinase (≥ 3 ULN). A single deviation from the above values is&#xD;
               acceptable and will not exclude the participant, unless specifically advised by the&#xD;
               Investigator.&#xD;
  &#xD;
            -  Participant has clinically relevant chronic or acute infectious illnesses or febrile&#xD;
               infections within 2 weeks prior to the first scheduled study drug administration&#xD;
  &#xD;
            -  Participant has gastrointestinal bleeding issues, e.g., Gastroesophageal Reflux&#xD;
               Disease (GERD), Peptic Ulcer Disease (PUD)&#xD;
  &#xD;
            -  Participant has a hospital admission or major surgery within 30 days prior to&#xD;
               randomization.&#xD;
  &#xD;
            -  Participant has a donation or blood collection of more than 1 unit (approximately 450&#xD;
               mL(milliliter)) of blood (or blood products) or acute loss of blood during the 30 days&#xD;
               prior to randomization.&#xD;
  &#xD;
            -  Participant has a history of alcohol abuse, prescription drug abuse, or illicit drug&#xD;
               use within 6 months prior to Screening.&#xD;
  &#xD;
            -  Participant meets eligibility criteria, but study is filled&#xD;
  &#xD;
            -  Participant who is an investigational site staff member directly involved in the&#xD;
               conduct of the study and his/her family members, site staff member otherwise&#xD;
               supervised by the Investigator, or participant who is a Amzell B.V. employee directly&#xD;
               involved in the conduct of the study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Irina Krause, MD</last_name>
      <phone>(201)336-1175</phone>
      <email>ikrause@tklresearch.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>TKL Research</name>
        <address>
          <city>Fair Lawn</city>
          <state>New Jersey</state>
          <zip>07410</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Irina Krause</last_name>
        <email>ikrause@tklresearch.com</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 7, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diclofenac</mesh_term>
    </intervention_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/NCT05968482
  org study id: AMZ001-008
  nct id: NCT05968482
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this clinical trial is to compare drug exposure from two different products
        (AMZ001 and Diclofenac Sodium 1% Gel) in healthy participants on Day 7 after repeated topical
        administrations for 7 days.
  
        Participants will receive, in a crossover design, three different treatments
  
          -  AMZ001 Low dose
  
          -  AMZ001 High dose
  
          -  Diclofenac Sodium 1% Gel
  
        Safety and tolerability of AMZ001 will be also investigated.
  On their both knees, participants will apply once daily either low dose of AMZ001 or high
        dose of AMZ001 for 7 consecutive days. Participants will also apply Diclofenac Sodium 1% Gel
        as per label information on each knee.
  
        Intensive pharmacokinetic assessment (blood samplings) will be performed on the first day of
        application (Day 1) as well as on the last day of application (Day 7).
  
        Each participant will receive each of the three treatments in a randomized manner. Between
        each treatment, participant will not receive any of the three tested therapies between 3
        weeks before receiving the next therapy. (washout period)
  
        Participants will stay on the clinical unit only during each period of treatment but not
        during washout period.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Compare exposure to diclofenac
  time frame: Day 7
  description: Area under the curve from time zero to 24 hours and maximum (peak) plasma drug concentration
  measure: Pharmacokinetic parameter - Cmin
  time frame: Day 7
  description: Minimum plasma drug concentration (Cmin)
  measure: Pharmacokinetic parameter - Tmax
  time frame: Day 7
  description: Time to reach maximum plasma concentration (Tmax)
  measure: Pharmacokinetic parameter - Ke
  time frame: Day 7
  description: Terminal disposition rate constant (Ke)
  measure: Pharmacokinetic parameter - Cavg
  time frame: Day 7
  description: Average plasma concentration (Cavg)
  measure: Pharmacokinetic parameter - Cmax
  time frame: Day 1
  description: Maximum plasma drug concentration (Cmax)
  measure: Pharmacokinetic parameter - Tmax
  time frame: Day 1
  description: Time to reach maximum plasma concentration
  measure: Pharmacokinetic parameter - Cavg
  time frame: Day 1
  description: Average plasma concentration
  measure: Local tolerability
  time frame: Day 1 to Day 7
  description: Incidence of application site reactions according to the terminology of the International Contact Dermatitis Research Group
  arm group label: AMZ001 Low dose
  arm group type: Experimental
  description: AMZ001 applied once daily for 7 consecutive days
  arm group label: AMZ001 High dose
  arm group type: Experimental
  description: AMZ001 applied once daily for 7 consecutive days
  arm group label: Diclofenac Sodium 1% Gel
  arm group type: Active Comparator
  description: Reference product applied four-times daily for 7 consecutive days
  intervention type: Drug
  intervention name: Diclofenac Sodium Gel
  description: Topical application on both knees
  arm group label: AMZ001 High dose
  arm group label: AMZ001 Low dose
  arm group label: Diclofenac Sodium 1% Gel
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Irina Krause, MD
  phone: (201)336-1175
  email: ikrause@tklresearch.com
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Diclofenac
  sharing ipd: No