<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/NCT04468425</url>
  </required_header>
  <id_info>
    <org_study_id>AC-1101-PK-001</org_study_id>
    <nct_id>NCT04468425</nct_id>
  </id_info>
  <brief_title>Tofacitinib Citrate Topical Gel 3.2% FDA BA Bridging Study</brief_title>
  <official_title>Open-label, Fixed-sequence, Two-period Comparative Bioavailability Study of Tofacitinib From Repeated Topical Applications of Tofacitinib Citrate Topical Gel 3.2% to Single Oral Administration of Xeljanz 5 mg Tablet in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TWi Biotechnology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TWi Biotechnology, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, single center, open-label, fixed sequence, two-period pharmacokinetic (PK)&#xD;
      study to evaluate the safety and relative systemic bioavailability of topical and oral&#xD;
      tofacitinib formulations in approximately 14 healthy subjects. Participants will receive a&#xD;
      single oral dose of tofacitinib 5 mg tablet in Period 1 of the study followed by a 7-day&#xD;
      washout period. In Period 2, participants will receive repeat administration of Tofacitinib&#xD;
      Citrate Topical Gel 3.2% BID for 14 days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Actual">December 21, 2020</completion_date>
  <primary_completion_date type="Actual">December 21, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Plasma Concentration [Cmax] of tofacitinib from single oral dosing in Period 1</measure>
    <time_frame>Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under Curve [AUC] of tofacitinib from single oral dosing in Period 1</measure>
    <time_frame>Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration [Cmax] of tofacitinib from repeat topical dosing in Period 2</measure>
    <time_frame>Day 8</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under Curve [AUC] of tofacitinib from repeat topical dosing in Period 2</measure>
    <time_frame>Day 8</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration [Cmax] of tofacitinib from repeat topical dosing in Period 2</measure>
    <time_frame>Day 21</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under Curve [AUC] of tofacitinib from repeat topical dosing in Period 2</measure>
    <time_frame>Day 21</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of Tofacitinib Citrate Topical Gel 3.2% as assessed by treatment-emergent adverse events and Dermal Reaction Scoring, respectively.</measure>
    <time_frame>Day 24</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Pharmacokinetic Study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Period 1 (Day 1) and 2 (Day 8 - Day 21) separated by 7-day washout period. Period 1: A single 5 mg tofacitinib tablet will be administered orally on Day 1.&#xD;
Period 2: Repeat dosing of Tofacitinib Citrate Topical Gel 3.2% to approximately 10% BSA in the morning of Day 8 and twice daily from Day 9 to Day 20 with the last dose in the morning of Day 21.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib Citrate</intervention_name>
    <description>Period 1: Xelijanz® 5 mg tablet (tofacitinib citrate) for single oral dosing. Period 2: Tofacitinib Citrate Topical Gel 3.2% for repeat topical dosing BID for 14 days.</description>
    <arm_group_label>Pharmacokinetic Study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, smoker (no more than 25 cigarettes or equivalent daily) or non-smoker,&#xD;
             ≥18 and ≤60 years of age, with BMI &gt;18.5 and &lt;30.0 kg/m2 and body weight ≥50.0 kg for&#xD;
             males and ≥45.0 kg for females.&#xD;
&#xD;
          2. Healthy as defined by:&#xD;
&#xD;
               1. The absence of clinically significant illness. Subjects vomiting within 24 hours&#xD;
                  pre dose will be carefully evaluated for upcoming illness/disease. Inclusion pre&#xD;
                  dosing is at the discretion of the Investigator;&#xD;
&#xD;
               2. The absence of clinically significant history of dermatological, neurological,&#xD;
                  endocrine, cardiovascular, respiratory, hematological, immunological,&#xD;
                  psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.&#xD;
&#xD;
          3. Females of childbearing potential who are sexually active with a male partner must be&#xD;
             willing to use one of the following acceptable contraceptive methods throughout the&#xD;
             study and for 30 days after the last study drug administration:&#xD;
&#xD;
               1. Intra-uterine contraceptive device without hormone release system placed at least&#xD;
                  4 weeks prior to study drug administration;&#xD;
&#xD;
               2. Male condom with intravaginally applied spermicide started at least 21 days prior&#xD;
                  to study drug administration;&#xD;
&#xD;
               3. Sterile male partner (vasectomized since at least 6 months).&#xD;
&#xD;
          4. Absence of excessive body hair at the topical application site, or willing to have&#xD;
             excess body hair removed prior to dosing.&#xD;
&#xD;
          5. Capable of consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of any clinically significant abnormality at physical examination, clinically&#xD;
             significant abnormal laboratory assessment or positive test for hepatitis B, hepatitis&#xD;
             C, or HIV found during medical screening.&#xD;
&#xD;
          2. Positive urine drug screen or alcohol breath test at screening.&#xD;
&#xD;
          3. History of allergic reactions to tofacitinib or other related drugs, or to any&#xD;
             excipient in the formulation.&#xD;
&#xD;
          4. Positive pregnancy test at screening.&#xD;
&#xD;
          5. Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood&#xD;
             pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or&#xD;
             over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening.&#xD;
&#xD;
          6. History of significant alcohol abuse within 1 year prior to screening or regular use&#xD;
             of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol&#xD;
             per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).&#xD;
&#xD;
          7. History of significant drug abuse within 1 year prior to screening or use of soft&#xD;
             drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs&#xD;
             (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and&#xD;
             amphetamine derivatives) within 1 year prior to screening.&#xD;
&#xD;
          8. Participation in a clinical research study involving the administration of an&#xD;
             investigational or marketed drug or device within 30 days prior to the first dosing,&#xD;
             administration of a biological product in the context of a clinical research study&#xD;
             within 90 days prior to the first dosing, or concomitant participation in an&#xD;
             investigational study involving no drug or device administration.&#xD;
&#xD;
          9. Use of medications for the timeframes specified below, with the exception of&#xD;
             medications exempted by the Investigator on a case-by-case basis because they are&#xD;
             judged unlikely to affect the pharmacokinetic profile of the study drug or subject&#xD;
             safety e.g. topical drug products without significant systemic absorption (not&#xD;
             including topical drug products administered to the gel application site):&#xD;
&#xD;
               1. Prescription medications within 14 days prior to the first dosing;&#xD;
&#xD;
               2. Over-the-counter products and natural health products (including herbal remedies,&#xD;
                  homeopathic and traditional medicines, probiotics, food supplements such as&#xD;
                  vitamins, minerals, amino acids, essential fatty acids, and protein supplements&#xD;
                  used in sports) within 7 days prior to the first dosing, with the exception of&#xD;
                  the occasional use of acetaminophen (up to 2 g daily);&#xD;
&#xD;
               3. Depot injection or implant of any drug within 3 months prior to the first dosing;&#xD;
&#xD;
               4. Any drugs known to induce or inhibit hepatic drug metabolism via the CYP3A4 and&#xD;
                  CYP2C19 enzymes within 30 days prior to first dose;&#xD;
&#xD;
                    -  Examples of inducers for CYP3A4 include barbiturates, carbamazepine,&#xD;
                       phenytoin, glucocorticoids, St. John's wort, etc.&#xD;
&#xD;
                    -  Examples of inhibitors for CYP3A4 include HIV antivirals, clarithromycin,&#xD;
                       ciprofloxacin, gestodene, etc.&#xD;
&#xD;
                    -  Examples of inducers for CYP2C19 include carbamazepine, norethindrone,&#xD;
                       prednisone, rifampicin, etc.&#xD;
&#xD;
                    -  Examples of inhibitors for CYP2C19 include proton pump inhibitors,&#xD;
                       fluoxetine, ketoconazole, etc.&#xD;
&#xD;
         10. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding&#xD;
             volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than&#xD;
             499 mL within 56 days prior to the first dosing.&#xD;
&#xD;
         11. Breast-feeding subject.&#xD;
&#xD;
         12. History of active tuberculosis or exposure to endemic areas within 8 weeks prior to&#xD;
             QuantiFERON®-TB testing performed at screening.&#xD;
&#xD;
         13. Positive QuantiFERON®-TB indicating possible tuberculosis infection.&#xD;
&#xD;
         14. Immunization with a live attenuated vaccine within 1 month prior to dosing or planned&#xD;
             vaccination during the course of the study.&#xD;
&#xD;
         15. History of clinically significant opportunistic infection e.g. invasive candidiasis or&#xD;
             pneumocystis pneumonia.&#xD;
&#xD;
         16. Serious local infection e.g. cellulitis, abscess, or systemic infection e.g.&#xD;
             septicemia, within 3 months prior to screening.&#xD;
&#xD;
         17. Presence of fever (body temperature &gt;37.6 °C) e.g. a fever associated with a&#xD;
             symptomatic viral or bacterial infection, within 2 weeks prior to the first dosing.&#xD;
&#xD;
         18. Presence of sunburn at the gel application site, or excessive exposure to ultraviolet&#xD;
             light such as sunlight or a tanning lamp, or recent use of laser at the gel&#xD;
             application areas that would prevent a safe application of the gel formulation as&#xD;
             judged by the Investigator, within 7 days before the gel application.&#xD;
&#xD;
         19. Presence of tattoos or significant skin aberrations at the gel application site, which&#xD;
             in the opinion of the investigator, would interfere with the ability to perform an&#xD;
             accurate dermal reaction assessment.&#xD;
&#xD;
         20. Any reason that, in the opinion of the Investigator, would prevent the subject from&#xD;
             participating in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Syneos Health Facility</name>
      <address>
        <city>Québec</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>November 25, 2021</last_update_submitted>
  <last_update_submitted_qc>November 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2021</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>Tofacitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 4, 2022</submitted>
    <returned>September 13, 2023</returned>
  </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/NCT04468425
org study id: AC-1101-PK-001
nct id: NCT04468425
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1, single center, open-label, fixed sequence, two-period pharmacokinetic (PK)
      study to evaluate the safety and relative systemic bioavailability of topical and oral
      tofacitinib formulations in approximately 14 healthy subjects. Participants will receive a
      single oral dose of tofacitinib 5 mg tablet in Period 1 of the study followed by a 7-day
      washout period. In Period 2, participants will receive repeat administration of Tofacitinib
      Citrate Topical Gel 3.2% BID for 14 days.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Other
masking: None (Open Label)
measure: Maximum Plasma Concentration [Cmax] of tofacitinib from single oral dosing in Period 1
time frame: Day 1
measure: Area Under Curve [AUC] of tofacitinib from single oral dosing in Period 1
time frame: Day 1
measure: Maximum Plasma Concentration [Cmax] of tofacitinib from repeat topical dosing in Period 2
time frame: Day 8
measure: Area Under Curve [AUC] of tofacitinib from repeat topical dosing in Period 2
time frame: Day 8
measure: Maximum Plasma Concentration [Cmax] of tofacitinib from repeat topical dosing in Period 2
time frame: Day 21
measure: Area Under Curve [AUC] of tofacitinib from repeat topical dosing in Period 2
time frame: Day 21
measure: Safety and tolerability of Tofacitinib Citrate Topical Gel 3.2% as assessed by treatment-emergent adverse events and Dermal Reaction Scoring, respectively.
time frame: Day 24
arm group label: Pharmacokinetic Study
arm group type: Experimental
description: Period 1 (Day 1) and 2 (Day 8 - Day 21) separated by 7-day washout period. Period 1: A single 5 mg tofacitinib tablet will be administered orally on Day 1.
Period 2: Repeat dosing of Tofacitinib Citrate Topical Gel 3.2% to approximately 10% BSA in the morning of Day 8 and twice daily from Day 9 to Day 20 with the last dose in the morning of Day 21.
intervention type: Drug
intervention name: Tofacitinib Citrate
description: Period 1: Xelijanz® 5 mg tablet (tofacitinib citrate) for single oral dosing. Period 2: Tofacitinib Citrate Topical Gel 3.2% for repeat topical dosing BID for 14 days.
arm group label: Pharmacokinetic Study
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Tofacitinib
sharing ipd: No
submitted: November 4, 2022
returned: September 13, 2023