<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/NCT03229798</url>
  </required_header>
  <id_info>
    <org_study_id>REC-0000330, Ver 1</org_study_id>
    <nct_id>NCT03229798</nct_id>
  </id_info>
  <brief_title>Sofusa System With Sumatriptan (KC5010) Phase 1 Dose Escalation Safety and PK Study (KCC-SMT-002)</brief_title>
  <acronym>KCC-SMT-002</acronym>
  <official_title>An Open-Label Phase 1 Study to Establish the Pharmacokinetics and Safety of Sumatriptan Succinate Administered Via the Sofusa™ DoseConnect™ System at Escalating Doses Compared to Oral Imitrex® Single 100 mg Dose in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sorrento Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kimberly-Clark Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sorrento Therapeutics, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study KCC-SMT-002, is a Phase 1, single-site, open-label, non-randomized, crossover, flexible&#xD;
      dose design study to investigate the pharmacokinetic (PK) and safety comparing the Sofusa™&#xD;
      system with sumatriptan (KC5010) to Imitrex® oral tablets in 17 healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2018</start_date>
  <completion_date type="Actual">March 28, 2018</completion_date>
  <primary_completion_date type="Actual">March 28, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PK Cmax</measure>
    <time_frame>48 hours after dosing begins</time_frame>
    <description>Pharmacokinetic profile with Cmax (maximum concentration) of drug in blood, ng/mL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK AUC</measure>
    <time_frame>48 hours after dosing begins</time_frame>
    <description>Pharmacokinetic profile AUC (area under the curve) of drug in blood, ng-hr/mL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dermatological skin response (Draize scale)</measure>
    <time_frame>From Predose to 168 hours after device application</time_frame>
    <description>Skin response as measured on modified Draize scale (erythema, edema, etc.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain of application and wear (VAS scale)</measure>
    <time_frame>Upon application and after wear</time_frame>
    <description>Pain as reported on Visual Analog Scale</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Migraine Disorders</condition>
  <arm_group>
    <arm_group_label>Sumatriptan Succinate Oral Tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>100 mg oral tablet commercial Imitrex sumatriptan succinate tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sofusa Profile #1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination device for transdermal delivery of sumatriptan succinate Current approved dose (SC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sofusa Dose Profile #2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sofusa Dose Profile #3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sofusa Dose Profile #4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sofusa Dose Profile #5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from prior Sofusa Dose Profile #2-4</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sumatriptan Succinate Oral Tablet</intervention_name>
    <description>Sumatriptan succinate commercial Imitrex 100 mg tablet</description>
    <arm_group_label>Sumatriptan Succinate Oral Tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Transdermal delivery of sumatriptan succinate</intervention_name>
    <description>Sumatriptan succinate transdermal drug delivery system</description>
    <arm_group_label>Sofusa Dose Profile #2</arm_group_label>
    <arm_group_label>Sofusa Dose Profile #3</arm_group_label>
    <arm_group_label>Sofusa Dose Profile #4</arm_group_label>
    <arm_group_label>Sofusa Dose Profile #5</arm_group_label>
    <arm_group_label>Sofusa Profile #1</arm_group_label>
    <other_name>Sofusa DoseDisc</other_name>
    <other_name>Sofusa DoseConnect</other_name>
    <other_name>KC5010</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able to give voluntary written informed consent (personally signed and dated) and&#xD;
             HIPPA Authorization prior to any study related procedures.&#xD;
&#xD;
          2. Available to participate for the entire study period.&#xD;
&#xD;
          3. Be a male or female person between 18 and 55 years (inclusive) of age.&#xD;
&#xD;
          4. Healthy as determined by the investigator based on a medical evaluation including&#xD;
             history, physical examination, electrocardiogram (ECG), and laboratory tests.&#xD;
&#xD;
          5. Have systolic blood pressure (sitting) of &lt; 140 mmHg and diastolic blood pressure of &lt;&#xD;
             90 mmHg after 5 minutes of rest. Minor excursions in blood pressure outside of this&#xD;
             range may be acceptable if determined not to be clinically significant by the study&#xD;
             physician or medical monitor.&#xD;
&#xD;
          6. Have resting pulse rate (sitting) within normal range of 60-100 bpm. Minor excursions&#xD;
             in resting pulse outside of this range may be acceptable if determined not to be&#xD;
             clinically significant by the study physician or the medical monitor.&#xD;
&#xD;
          7. Females must be either postmenopausal for at least 1 year, surgically sterile&#xD;
             (bilateral oophorectomy, tubal ligation, tubal occlusion, hysterectomy), or using&#xD;
             adequate contraception from screening until 90 days after completion of study&#xD;
             participation. Adequate contraception is defined as true abstinence, a vasectomized&#xD;
             partner, or one of the following in combination with a diaphragm, cervical cap, or a&#xD;
             condom:&#xD;
&#xD;
               -  Hormonal contraceptives (oral, implant, patch, injection)&#xD;
&#xD;
               -  Intrauterine device&#xD;
&#xD;
             Males must use adequate contraception and must not donate sperm from first admission&#xD;
             to the clinical research center until 90 days after completion of study participation.&#xD;
             Adequate contraception is defined as true abstinence, vasectomy, a partner who is&#xD;
             surgically sterile (bilateral oophorectomy, tubal ligation, tubal occlusion,&#xD;
             hysterectomy), or one of the following in combination with a diaphragm, cervical cap,&#xD;
             or a condom:&#xD;
&#xD;
               -  Hormonal contraceptives (oral, implant, patch, injection)&#xD;
&#xD;
               -  Intrauterine device&#xD;
&#xD;
          8. Have a body weight above 50 kg and below 90 kg (inclusive).&#xD;
&#xD;
          9. Be able to communicate effectively with the study personnel and understand and comply&#xD;
             with all study requirements.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Women who are pregnant or lactating.&#xD;
&#xD;
          2. Current use or has used tobacco- or nicotine-containing products (e.g., cigarettes,&#xD;
             cigars, chewing tobacco, snuff, etc.) 30 days prior to investigational product&#xD;
             administration. A cotinine test (with a cut-off of 200 mg) will be performed at&#xD;
             screening and admission to the study center.&#xD;
&#xD;
          3. Recent history (i.e. within 2 years) of alcohol abuse, illicit drug use, or&#xD;
             significant mental illness.&#xD;
&#xD;
          4. Positive screen for substances of abuse.&#xD;
&#xD;
          5. A positive screening result for human immunodeficiency virus (HIV) antibody, Hepatitis&#xD;
             B surface antigen (HBsAg), or Hepatitis C antibody (anti-HCV).&#xD;
&#xD;
          6. Any disease or condition (medical or surgical) that might compromise a major body&#xD;
             system (e.g. cardiovascular, respiratory, etc.) or conditions that may interfere with&#xD;
             the absorption, distribution, metabolism, or excretion of the study medication.&#xD;
&#xD;
          7. Any bleeding disorders or use of anticoagulants.&#xD;
&#xD;
          8. Any conditions (e.g. diabetes, edema, scleroderma) or receiving medications (e.g.&#xD;
             steroids, antibiotics) that alter skin integrity and/or healing. Any known condition&#xD;
             or receiving medications causing hypo/hyperpigmentation or photosensitivity.&#xD;
&#xD;
          9. Presence or history of hypertension or other cardiovascular abnormalities such as, but&#xD;
             not limited to, myocardial infarction, heart failure, arrhythmia, stroke, or&#xD;
             peripheral vascular disease or any other cardiovascular disease that requires the&#xD;
             subject to wear a pacemaker.&#xD;
&#xD;
         10. Use of a drug therapy known to induce or inhibit hepatic drug metabolism within 30&#xD;
             days prior to the Treatment visit for dosing.&#xD;
&#xD;
         11. Patient has received a live attenuated vaccine within the 4 weeks prior to treatment&#xD;
             or plans to receive one during the study.&#xD;
&#xD;
         12. Febrile illness within 7 days of Treatment visit for dosing.&#xD;
&#xD;
         13. Has a positive history or known sensitivity to sumatriptan or other triptans.&#xD;
&#xD;
         14. Any history of sensitivity to methylene blue, fluorescein or calcein, or other similar&#xD;
             dye product.&#xD;
&#xD;
         15. Subjects who have used ergotamine-containing or ergot-type medications (like&#xD;
             dihydrogergotamine or methysergide) within the past week. The Imitrex® label specifies&#xD;
             that these medication are contraindicated within 24 hours of use.&#xD;
&#xD;
         16. Diagnosed with ischemic bowel disease or severe hepatic impairment which are known&#xD;
             contraindications to sumatriptan.&#xD;
&#xD;
         17. Concomitant therapy with the following medications which have significant drug&#xD;
             interactions with sumatriptan: selective serotonin reuptake inhibitors (SSRIs),&#xD;
             serotonin/norepinephrine reuptake inhibitor (SNRIs), tricyclic antidepressants, and&#xD;
             monomine oxidase (MAO) inhibitors due to an increased risk of serotonin syndrome.&#xD;
             Subjects receiving these medications may enroll in the study if these medications have&#xD;
             been discontinued for 5 or more half-lives prior to the first Treatment visit.&#xD;
&#xD;
         18. Subjects who are currently taking prescription or over-the-counter medications&#xD;
             (including vitamins and herbal preparations) that could interfere with the evaluation&#xD;
             or the safety of the subject, as determined by the Investigator.&#xD;
&#xD;
         19. Participation in the treatment phase of a clinical study or receipt of an&#xD;
             investigational drug or medical device within 30 days prior to the Treatment visit for&#xD;
             dosing.&#xD;
&#xD;
         20. History of difficulty with phlebotomy procedures.&#xD;
&#xD;
         21. Donated blood (&gt;400 mL) or blood products within 45 days prior to the Treatment visit&#xD;
             for dosing.&#xD;
&#xD;
         22. Subjects who have skin conditions or tattoos extensive enough to cover areas where the&#xD;
             device is to be applied.&#xD;
&#xD;
         23. Any history of skin contact sensitivity to metals, plastics or adhesives.&#xD;
&#xD;
         24. Has a condition that, in the opinion of the Investigator, may increase the risk to the&#xD;
             subject and/or the interpretation of the data.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wayne L Harper, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Carolina Phase I Research, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carolina Phase 1 Research</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Imitrex_Tablets/pdf/IMITREX-TABLETS-PI-PIL.PDF</url>
    <description>Imitrex® oral prescribing information (November 2013)</description>
  </link>
  <reference>
    <citation>Kam KR, Walsh LA, Bock SM, Koval M, Fischer KE, Ross RF, Desai TA. Nanostructure-mediated transport of biologics across epithelial tissue: enhancing permeability via nanotopography. Nano Lett. 2013 Jan 9;13(1):164-71. doi: 10.1021/nl3037799. Epub 2012 Dec 24.</citation>
    <PMID>23186530</PMID>
  </reference>
  <reference>
    <citation>Walsh L, Ryu J, Bock S, Koval M, Mauro T, Ross R, Desai T. Nanotopography facilitates in vivo transdermal delivery of high molecular weight therapeutics through an integrin-dependent mechanism. Nano Lett. 2015 Apr 8;15(4):2434-41. doi: 10.1021/nl504829f. Epub 2015 Mar 27.</citation>
    <PMID>25790174</PMID>
  </reference>
  <reference>
    <citation>Owen K, Hartley K, Tucker ML, Parkinson MM, Tweats DJ, Jackson MR. The preclinical toxicological evaluation of sumatriptan. Hum Exp Toxicol. 1995 Dec;14(12):959-73. doi: 10.1177/096032719501401205.</citation>
    <PMID>8962747</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>August 5, 2022</last_update_submitted>
  <last_update_submitted_qc>August 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2022</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>Migraine Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sumatriptan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03229798
org study id: REC-0000330, Ver 1
nct id: NCT03229798
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
Study KCC-SMT-002, is a Phase 1, single-site, open-label, non-randomized, crossover, flexible
      dose design study to investigate the pharmacokinetic (PK) and safety comparing the Sofusa™
      system with sumatriptan (KC5010) to Imitrex® oral tablets in 17 healthy volunteers.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PK Cmax
time frame: 48 hours after dosing begins
description: Pharmacokinetic profile with Cmax (maximum concentration) of drug in blood, ng/mL
measure: PK AUC
time frame: 48 hours after dosing begins
description: Pharmacokinetic profile AUC (area under the curve) of drug in blood, ng-hr/mL
measure: Dermatological skin response (Draize scale)
time frame: From Predose to 168 hours after device application
description: Skin response as measured on modified Draize scale (erythema, edema, etc.)
measure: Pain of application and wear (VAS scale)
time frame: Upon application and after wear
description: Pain as reported on Visual Analog Scale
arm group label: Sumatriptan Succinate Oral Tablet
arm group type: Active Comparator
description: 100 mg oral tablet commercial Imitrex sumatriptan succinate tablet
arm group label: Sofusa Profile #1
arm group type: Experimental
description: Combination device for transdermal delivery of sumatriptan succinate Current approved dose (SC)
arm group label: Sofusa Dose Profile #2
arm group type: Experimental
description: Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #1
arm group label: Sofusa Dose Profile #3
arm group type: Experimental
description: Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #2
arm group label: Sofusa Dose Profile #4
arm group type: Experimental
description: Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #3
arm group label: Sofusa Dose Profile #5
arm group type: Experimental
description: Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from prior Sofusa Dose Profile #2-4
intervention type: Drug
intervention name: Sumatriptan Succinate Oral Tablet
description: Sumatriptan succinate commercial Imitrex 100 mg tablet
arm group label: Sumatriptan Succinate Oral Tablet
intervention type: Combination Product
intervention name: Transdermal delivery of sumatriptan succinate
description: Sumatriptan succinate transdermal drug delivery system
arm group label: Sofusa Dose Profile #2
arm group label: Sofusa Dose Profile #3
arm group label: Sofusa Dose Profile #4
arm group label: Sofusa Dose Profile #5
arm group label: Sofusa Profile #1
other name: Sofusa DoseDisc
other name: Sofusa DoseConnect
other name: KC5010
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wayne L Harper, MD
role: Principal Investigator
affiliation: Carolina Phase I Research, LLC
facility: 
country: United States
url: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Imitrex_Tablets/pdf/IMITREX-TABLETS-PI-PIL.PDF
description: Imitrex® oral prescribing information (November 2013)
citation: Kam KR, Walsh LA, Bock SM, Koval M, Fischer KE, Ross RF, Desai TA. Nanostructure-mediated transport of biologics across epithelial tissue: enhancing permeability via nanotopography. Nano Lett. 2013 Jan 9;13(1):164-71. doi: 10.1021/nl3037799. Epub 2012 Dec 24.
PMID: 23186530
citation: Walsh L, Ryu J, Bock S, Koval M, Mauro T, Ross R, Desai T. Nanotopography facilitates in vivo transdermal delivery of high molecular weight therapeutics through an integrin-dependent mechanism. Nano Lett. 2015 Apr 8;15(4):2434-41. doi: 10.1021/nl504829f. Epub 2015 Mar 27.
PMID: 25790174
citation: Owen K, Hartley K, Tucker ML, Parkinson MM, Tweats DJ, Jackson MR. The preclinical toxicological evaluation of sumatriptan. Hum Exp Toxicol. 1995 Dec;14(12):959-73. doi: 10.1177/096032719501401205.
PMID: 8962747
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Sumatriptan
sharing ipd: Undecided