<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/NCT03229291</url>
  </required_header>
  <id_info>
    <org_study_id>SM04755-TOP-01</org_study_id>
    <nct_id>NCT03229291</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SM04755 Following Topical Administration to Healthy Subjects</brief_title>
  <official_title>A Phase 1, Single-Center, Randomized, Single-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SM04755 Following Topical Administration to Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biosplice Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biosplice Therapeutics, Inc.</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>
      This study is a single-center, randomized, single-blind, placebo-controlled, multiple&#xD;
      ascending dose study of SM04755 solution applied topically once daily for 14 days to intact&#xD;
      skin overlying the inner thigh of healthy subjects at an estimated body surface area (BSA) of&#xD;
      80 cm^2. Dosing cohorts will consist of 8 subjects who will be randomized 3:1&#xD;
      (SM04755:placebo).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 3, 2016</start_date>
  <completion_date type="Actual">June 11, 2017</completion_date>
  <primary_completion_date type="Actual">June 11, 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events (AEs)</measure>
    <time_frame>Day 28</time_frame>
    <description>Incidence and severity of AEs events during the treatment and observation periods of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of clinical laboratory abnormalities</measure>
    <time_frame>Day 28</time_frame>
    <description>Incidence and severity of clinical laboratory measurements that are outside the normal range</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in vital signs: blood pressure</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in blood pressure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in vital signs: temperature</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in vital signs: respiratory rate</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in respiratory rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in vital signs: pulse rate</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in pulse rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in electrocardiogram (ECG) parameters</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in 12-lead ECG parameters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK): Cmax</measure>
    <time_frame>Day 1</time_frame>
    <description>Maximum plasma concentration (Cmax) estimate for SM04755 following first dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK):tmax</measure>
    <time_frame>Day 1</time_frame>
    <description>Time to Cmax estimate for SM04755 following first dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK): AUC</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve (AUC) estimate for SM04755 following first dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK):half-life</measure>
    <time_frame>Day 1</time_frame>
    <description>Plasma terminal phase half-life estimate for SM04755 following first dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK):Cmax</measure>
    <time_frame>Day 14</time_frame>
    <description>Maximum plasma concentration (Cmax) estimate for SM04755 following last dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK):tmax</measure>
    <time_frame>Day 14</time_frame>
    <description>Time to Cmax estimate for SM04755 following last dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK): AUC</measure>
    <time_frame>Day 14</time_frame>
    <description>AUC estimate for SM04755 following last dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma pharmacokinetics (PK):half-life</measure>
    <time_frame>Day 14</time_frame>
    <description>Plasma terminal phase half-life estimate for SM04755 following last dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in skin score assessment: erythema</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in erythema skin score assessment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in skin score assessment: scaling</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in scaling skin score assessment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in skin score assessment: pruritus/itching</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in pruritus/itching skin score assessment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in skin score assessment: burning/stinging</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Change from baseline in burning/stinging skin score assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of AEs relative to exposure</measure>
    <time_frame>Day 28</time_frame>
    <description>Incidence and severity of AEs relative to measured plasma exposure to SM04755</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Tendinopathy</condition>
  <arm_group>
    <arm_group_label>Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Topical SM04755 solution (15 mg/mL) applied once per day for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mid Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Topical SM04755 solution (45 mg/mL) applied once per day for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Topical SM04755 solution (90 mg/mL) applied once per day for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vehicle</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vehicle solution applied once per day for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SM04755</intervention_name>
    <description>SM04755 is a small molecule inhibitor of the Wnt pathway.</description>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_label>Low Dose</arm_group_label>
    <arm_group_label>Mid Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vehicle</intervention_name>
    <description>Same formulation as topical SM04755 solution, without SM04755 included.</description>
    <arm_group_label>Vehicle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index of 18 to 30 kg/m^2 at study start&#xD;
&#xD;
          -  Subject must have read and understood the informed consent form, and must have signed&#xD;
             it prior to any study-related procedure being performed&#xD;
&#xD;
          -  Willingness to comply with all scheduled study visits, laboratory tests, contraception&#xD;
             requirements and other study procedures&#xD;
&#xD;
          -  Appropriate skin characteristics at site of application (inner thigh) (for example,&#xD;
             consistent pigmentation, no tattoos, no scarring or noted injury, no varicose veins or&#xD;
             structural repair)&#xD;
&#xD;
          -  Willing to avoid extensive sun exposure, phototherapy, or use of a tanning salon for&#xD;
             the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  Women of childbearing potential who are sexually active and are not willing to use a&#xD;
             highly effective method of birth control during the study period that includes double&#xD;
             barrier, intrauterine device (IUD), or hormonal contraceptive combined with single&#xD;
             barrier, or abstinence&#xD;
&#xD;
          -  Males who are sexually active and not willing to use a condom, and have a partner who&#xD;
             is capable of becoming pregnant, if neither has had surgery to become sterilized,&#xD;
             and/or who are not willing to use double barrier or whose partner is not using a&#xD;
             highly effective method of birth control (e.g., IUD or hormonal contraception combined&#xD;
             with single barrier).&#xD;
&#xD;
          -  History of, or current, skin disease (for example, psoriasis, atopic dermatitis,&#xD;
             seborrheic dermatitis, and skin cancer)&#xD;
&#xD;
          -  History of, or current, skin damage at the treatment site (inner thigh) (for example,&#xD;
             cuts, abrasion, sunburn, sun-damage, or scarring)&#xD;
&#xD;
          -  Phototherapy or use of a tanning salon 2 weeks prior to study start until end of the&#xD;
             study (Day 28)&#xD;
&#xD;
          -  History of, or current, allergy to investigational product/placebo ingredients&#xD;
&#xD;
          -  Known allergy to adhesive tape&#xD;
&#xD;
          -  Current evidence of malignancy or history of malignancy within the last 5 years prior&#xD;
             to study start; prior history of in situ cancer or basal or squamous cell skin cancer,&#xD;
             completely excised, is allowed&#xD;
&#xD;
          -  Treatment with an investigational product within 12 weeks prior to study start; the&#xD;
             last date of participation in the trial, not the last date of receipt of&#xD;
             investigational product, must be at least 12 weeks prior to study start&#xD;
&#xD;
          -  Use of any prescription or nonprescription drugs [except birth control or hormone&#xD;
             replacement therapy (HRT)], topical skin treatments on the application site (inner&#xD;
             thigh), vitamins, grapefruit/grapefruit juice, or dietary or herbal supplements within&#xD;
             14 days prior to study start&#xD;
&#xD;
          -  Blood donation of ≥ 1 pint (473 mL) within 56 days prior to study start or unwilling&#xD;
             to refrain from blood donation for the duration of the study&#xD;
&#xD;
          -  Plasma or platelet donation within 14 days prior to study start or unwilling to&#xD;
             refrain from plasma or platelet donation for the duration of the study&#xD;
&#xD;
          -  Unwilling to refrain from sperm donation for the duration of the study and until 90&#xD;
             days after dose administration&#xD;
&#xD;
          -  Prior or current latent or active tuberculosis (TB) or nontuberculous mycobacteria&#xD;
             infection.&#xD;
&#xD;
          -  Evidence of active infection or illness involving fever within 7 days prior to study&#xD;
             start&#xD;
&#xD;
          -  Occurrence of serious illness requiring hospitalization within 6 months prior to study&#xD;
             start&#xD;
&#xD;
          -  Regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for&#xD;
             men (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces&#xD;
             [45 mL] of hard liquor) within 6 months prior to study start&#xD;
&#xD;
          -  Use of tobacco- or nicotine-containing products (cigarettes, pipe, cigar, chewing&#xD;
             tobacco or nicotine gum, lozenges or patches) within 30 days prior to study start&#xD;
&#xD;
          -  A history of abuse of prescription or illicit drugs within 6 months prior to study&#xD;
             start&#xD;
&#xD;
          -  Marijuana use within 28 days prior to study start&#xD;
&#xD;
          -  Previous treatment with SM04755&#xD;
&#xD;
          -  Subjects who have a current or pending disability claim, workers' compensation, or&#xD;
             litigation(s) that may compromise response to treatment&#xD;
&#xD;
          -  Subjects who are immediate family members (spouse, parent, child, or sibling;&#xD;
             biological or legally adopted) of personnel directly affiliated with the study at the&#xD;
             investigative site, or are directly affiliated with the study at the investigative&#xD;
             site&#xD;
&#xD;
          -  Subjects employed by Samumed, LLC, or any of its affiliates or development partners&#xD;
             (that is, an employee, temporary contract worker, or designee) responsible for the&#xD;
             conduct of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yusuf Yazici, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Biosplice Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 18, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>July 21, 2017</last_update_submitted>
  <last_update_submitted_qc>July 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SM04755</keyword>
  <keyword>topical</keyword>
  <keyword>Samumed</keyword>
  <keyword>Wnt inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tendinopathy</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/NCT03229291
org study id: SM04755-TOP-01
nct id: NCT03229291
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is a single-center, randomized, single-blind, placebo-controlled, multiple
      ascending dose study of SM04755 solution applied topically once daily for 14 days to intact
      skin overlying the inner thigh of healthy subjects at an estimated body surface area (BSA) of
      80 cm^2. Dosing cohorts will consist of 8 subjects who will be randomized 3:1
      (SM04755:placebo).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence of adverse events (AEs)
time frame: Day 28
description: Incidence and severity of AEs events during the treatment and observation periods of the study
measure: Incidence of clinical laboratory abnormalities
time frame: Day 28
description: Incidence and severity of clinical laboratory measurements that are outside the normal range
measure: Change in vital signs: blood pressure
time frame: Baseline and Day 28
description: Change from baseline in blood pressure
measure: Change in vital signs: temperature
time frame: Baseline and Day 28
description: Change from baseline in temperature
measure: Change in vital signs: respiratory rate
time frame: Baseline and Day 28
description: Change from baseline in respiratory rate
measure: Change in vital signs: pulse rate
time frame: Baseline and Day 28
description: Change from baseline in pulse rate
measure: Change in electrocardiogram (ECG) parameters
time frame: Baseline and Day 28
description: Change from baseline in 12-lead ECG parameters
measure: Plasma pharmacokinetics (PK): Cmax
time frame: Day 1
description: Maximum plasma concentration (Cmax) estimate for SM04755 following first dose
measure: Plasma pharmacokinetics (PK):tmax
time frame: Day 1
description: Time to Cmax estimate for SM04755 following first dose
measure: Plasma pharmacokinetics (PK): AUC
time frame: Day 1
description: Area under the plasma concentration-time curve (AUC) estimate for SM04755 following first dose
measure: Plasma pharmacokinetics (PK):half-life
time frame: Day 1
description: Plasma terminal phase half-life estimate for SM04755 following first dose
measure: Plasma pharmacokinetics (PK):Cmax
time frame: Day 14
description: Maximum plasma concentration (Cmax) estimate for SM04755 following last dose
measure: Plasma pharmacokinetics (PK):tmax
time frame: Day 14
description: Time to Cmax estimate for SM04755 following last dose
measure: Plasma pharmacokinetics (PK): AUC
time frame: Day 14
description: AUC estimate for SM04755 following last dose
measure: Plasma pharmacokinetics (PK):half-life
time frame: Day 14
description: Plasma terminal phase half-life estimate for SM04755 following last dose
measure: Change in skin score assessment: erythema
time frame: Baseline and Day 28
description: Change from baseline in erythema skin score assessment
measure: Change in skin score assessment: scaling
time frame: Baseline and Day 28
description: Change from baseline in scaling skin score assessment
measure: Change in skin score assessment: pruritus/itching
time frame: Baseline and Day 28
description: Change from baseline in pruritus/itching skin score assessment
measure: Change in skin score assessment: burning/stinging
time frame: Baseline and Day 28
description: Change from baseline in burning/stinging skin score assessment
measure: Incidence of AEs relative to exposure
time frame: Day 28
description: Incidence and severity of AEs relative to measured plasma exposure to SM04755
arm group label: Low Dose
arm group type: Experimental
description: Topical SM04755 solution (15 mg/mL) applied once per day for 14 days
arm group label: Mid Dose
arm group type: Experimental
description: Topical SM04755 solution (45 mg/mL) applied once per day for 14 days
arm group label: High Dose
arm group type: Experimental
description: Topical SM04755 solution (90 mg/mL) applied once per day for 14 days
arm group label: Vehicle
arm group type: Placebo Comparator
description: Vehicle solution applied once per day for 14 days
intervention type: Drug
intervention name: SM04755
description: SM04755 is a small molecule inhibitor of the Wnt pathway.
arm group label: High Dose
arm group label: Low Dose
arm group label: Mid Dose
intervention type: Drug
intervention name: Vehicle
description: Same formulation as topical SM04755 solution, without SM04755 included.
arm group label: Vehicle
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Yusuf Yazici, M.D.
role: Study Director
affiliation: Biosplice Therapeutics, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tendinopathy