<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/NCT03803059</url>
  </required_header>
  <id_info>
    <org_study_id>Bellmed002</org_study_id>
    <nct_id>NCT03803059</nct_id>
  </id_info>
  <brief_title>Efficacy and Tolerability of SkinPen on Male and Female Subjects' Wrinkles of the Neck</brief_title>
  <official_title>A Single-Center Trial to Evaluate the Efficacy and Tolerability of SkinPen on Male and Female Subjects' Wrinkles of the Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bellus Medical, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bellus Medical, LLC</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This single-center, the clinical trial is being conducted over the course of 90 days followed&#xD;
      by 1-month and 6-month post-treatment visits in order to assess the efficacy and tolerability&#xD;
      of the Sponsor's SkinPen device when used by men and women with the wrinkles of the neck.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 32 subjects completed study participation.&#xD;
&#xD;
      At visit 1 (baseline), subjects were screened for eligibility criteria, and those who&#xD;
      qualified either completed day 1 procedures at the same visit or returned to the clinic up to&#xD;
      14 days after visit 1 to complete day 1 procedures at visit 2.&#xD;
&#xD;
      On days 1, 30, 60, and 90, after completion of visit assessments, doctors or fellows at the&#xD;
      testing facility (henceforth referred to as &quot;clinic&quot;) treated each subject's wrinkles of the&#xD;
      neck with SkinPen Precision System at depths of up to 2.5mm.&#xD;
&#xD;
      During the post-treatment period, Clinical evaluations were conducted at visit 2 (day 1),&#xD;
      visit 3 (day 30), visit 4 (day 60), visit 5 (day 90), visit 6 (1month post-treatment), and&#xD;
      visit 7 (3 months post-treatment)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2019</start_date>
  <completion_date type="Actual">January 10, 2020</completion_date>
  <primary_completion_date type="Actual">January 10, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of Wrinkle Severity Using the Lemperle Wrinkle Assessment Scale</measure>
    <time_frame>Day 1 and 3 Month Post Treatment</time_frame>
    <description>Wrinkling in the neck region will be assessed according to the following definitions:&#xD;
Class 0: No Wrinkles Class 1: Just perceptible wrinkle Class 2: Shallow wrinkles Class 3: Moderately deep wrinkle Class 4: Deep wrinkle, well-defined edges Class 5: Very deep wrinkle, redundant fold</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinician's Global Aesthetic Improvement Assessment (CGAIS)</measure>
    <time_frame>3 Month Post Treatment</time_frame>
    <description>This scale is completed in two steps:&#xD;
Based on a live assessment of the subject while referring to the subject's pre-treatment photographs of the neck, and&#xD;
Based on a comparison of the subject's pre-treatment photographs to the current post-treatment photographs of the neck.&#xD;
Rating and its Description&#xD;
1 --Very Much Improved: Optimal cosmetic result in this subject. 2--Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal for this subject.&#xD;
3-Improved: Obvious improvement in appearance from the initial condition, but re-treatment is indicated.&#xD;
4--No Change: The appearance is essentially the same as the original condition. 5--Worse: The appearance is worse than the original condition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Subject Global Aesthetic Improvement Scale (SGAIS)</measure>
    <time_frame>1 Month Post Treatment and 3 Month Post Treatment</time_frame>
    <description>Rating and Description&#xD;
-Very Much Improved: Optimal cosmetic result.&#xD;
-Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal.&#xD;
-Improved: Obvious improvement in appearance from the initial condition.&#xD;
-No Change: The appearance is essentially the same as the original condition.&#xD;
-Worse: The appearance is worse than the original condition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transepidermal Water Loss of the Left Neck by Biox Aquaflux</measure>
    <time_frame>Baseline, 3 Months post treatment</time_frame>
    <description>The severity of wrinkles is more due to increased UV exposure through the driver's side window on the left side of the face and neck, due to this reason, the Principal investigator performed the TEWL on the left side of the neck. This test was pre-specified in the protocol. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
Biox Aquaflux is used to measure transepidermal water loss (TEWL) measurements which evaluate barrier function of the skin epidermal layer to determine the progress of epidermal healing after treatment.&#xD;
Day 1 will be used as a baseline to analyze the change from baseline. TEWL is measured in g/m2/h. Normal rates of TEWL - from 2.3 g/m2/h to 44 g/m2/h - are compromised due to injury, infection, and/or severe damage as in the case of burns A decrease inTEWL reflects less water loss and an improvement in the skin's barrier properties; an absence of a change in treate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular Density Measurements by Optical Coherence Tomography(OCT)</measure>
    <time_frame>Baseline (Day 1) and 3-Month post Treatment</time_frame>
    <description>Vivosight, an Optical coherence tomography (OCT) device, is used to non-invasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. OCT measurements of the vascular density are reported in percentage (%) and were performed on the neck at 100 microns, 200 microns, and 500 microns. Scores multiplied by 1000 for analysis.&#xD;
An increase in value indicates an increase in thickness and vascular density and skin tissue density.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin Roughness Measurements by Optical Coherence Tomography(OCT)</measure>
    <time_frame>Baseline (Day 1) and 3 Months post treatment</time_frame>
    <description>Vivosight, an optical coherence tomography (OCT) device, was used to noninvasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. Roughness measurements were calculated from the histologic images using RA and RZ. Skin roughness is measured in micro-meters.&#xD;
Ra is the average roughness of a surface. Rz is the difference between the tallest &quot;peak&quot; and the deepest &quot;valley&quot; on the surface.&#xD;
A decrease in value indicates a decrease in skin roughness when Baseline and 3 months post-treatment are compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BTC 2000 Measurements- Energy Absorption</measure>
    <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
    <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure energy absorption of the skin.&#xD;
The units for these measurements are Energy absorption - mmHg*mm&#xD;
Decrease in values for energy absorption will be seen as Improvement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BTC 2000 Measurements for Skin Elasticity</measure>
    <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
    <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure Elasticity values of the skin.&#xD;
The units for these measurements are in % of the distance traveled in µm.&#xD;
A decrease case in values for elasticity will be seen as an improvement after the treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BTC 2000 Measurements for Skin Deformations</measure>
    <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
    <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure viscoelastic deformation, elastic deformation, and ultimate deformation values of the skin.&#xD;
The units for these measurements are in mm.&#xD;
A Decrease in values for these deformations will be seen as an Improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BTC 2000 Measurements for Stiffness</measure>
    <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
    <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used for stiffness. Stiffness is measure in mmHg/mm and an increase in values of BTC measurements for stiffness would be seen as an improvement upon treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Satisfaction Questionnaires</measure>
    <time_frame>1 month post treatment</time_frame>
    <description>Subjects completed a Sponsor-provided questionnaire regarding improvement in wrinkles, satisfaction with the treatment, and willingness to recommend the treatment to friends and family members</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ultrasound Measurements</measure>
    <time_frame>Day 1, 3 Months post treatment.</time_frame>
    <description>Ultrasound measurements were performed using a 75 MHz ultrasonic transducer interfaced to a DUB 6100 OEM System (Taberna Pro Medicum, Lüneburg, Germany). Density and skin thickness measurements were obtained from the scans and increases in these values suggest a thickening of the epidermal and dermal tissue.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Wrinkles</condition>
  <arm_group>
    <arm_group_label>Wrinkles of the Neck</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Microneedle treatment neck areas.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>SkinPen Precision</intervention_name>
    <description>Surgical instrument motors and accessories/attachments/Hydrogel</description>
    <arm_group_label>Wrinkles of the Neck</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        At least 20% of subjects will have Fitzpatrick skin types IV-VI Individuals who grade a 4&#xD;
        or higher on the Fitzpatrick Wrinkle Scale Individuals that desire correction of their&#xD;
        wrinkles Individuals willing to withhold aesthetic therapies to the areas of the neck being&#xD;
        treated or judged to potentially impact results by the Investigator.&#xD;
&#xD;
        Women of childbearing potential agree to take a urine pregnancy test at the Baseline visit&#xD;
        and 6-months post-treatment or when deemed by Investigator and/or Sponsor. This may be&#xD;
        changed to one monthly pregnancy test at the Sponsor's discretion. Women who are of&#xD;
        childbearing potential must have a negative urine pregnancy test result and must not be&#xD;
        lactating at the baseline visit. Women must be willing and able to use an acceptable method&#xD;
        of birth control (e.g. barrier methods used with a spermicidal agent, hormonal methods,&#xD;
        IUD, surgical sterilization, abstinence) during the study. Women will not be considered of&#xD;
        childbearing potential if one of the following conditions is documented on the medical&#xD;
        history:&#xD;
&#xD;
          -  Postmenopausal for at least 12 months prior to the study;&#xD;
&#xD;
          -  Without a uterus and/or both ovaries;&#xD;
&#xD;
          -  Bilateral tubal ligation at least 6 months prior to study enrollment. Women of child&#xD;
             bearing potential agree to take a urine pregnancy test at the Baseline visit and&#xD;
             6-months post-treatment or when deemed by Investigator and/or Sponsor. This may be&#xD;
             changed to one month pregnancy test at the Sponsor's discretion. Women who are of&#xD;
             childbearing potential must have a negative urine pregnancy test result and must not&#xD;
             be lactating at the baseline visit. Women must be willing and able to use an&#xD;
             acceptable method of birth control (e.g. barrier methods used with a spermicidal&#xD;
             agent, hormonal methods, IUD, surgical sterilization, abstinence) during the study.&#xD;
             Women will not be considered of childbearing potential if one of the following&#xD;
             conditions is documented on the medical history:&#xD;
&#xD;
          -  Postmenopausal for at least 12 months prior to the study;&#xD;
&#xD;
          -  Without a uterus and/or both ovaries;&#xD;
&#xD;
          -  Bilateral tubal ligation at least 6 months prior to study enrollment.&#xD;
&#xD;
        Individuals of child-bearing potential who use an acceptable method of contraception&#xD;
        throughout the study. Acceptable methods of birth control include:&#xD;
&#xD;
          1. Established use of hormonal methods of contraception (oral, injected, implanted,&#xD;
             patch, or vaginal ring).&#xD;
&#xD;
          2. Barrier methods of contraception with spermicide: condom or occlusive cap (diaphragm&#xD;
             or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.&#xD;
&#xD;
          3. Intrauterine device (IUD) or intrauterine system (IUS)&#xD;
&#xD;
          4. Surgical sterilization (e.g., vasectomy that has been confirmed effective by sperm&#xD;
             count check, tubal occlusion, hysterectomy, bilateral salpingectomy/oophorectomy)&#xD;
&#xD;
          5. Abstinence from heterosexual intercourse, when this is in line with the preferred and&#xD;
             usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation,&#xD;
             symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of&#xD;
             contraception.&#xD;
&#xD;
               -  Individuals that are willing to provide written informed consent and are able to&#xD;
                  read, speak, write, and understand English.&#xD;
&#xD;
               -  Individuals willing to sign a photography release.&#xD;
&#xD;
               -  Willingness to cooperate and participate by following study requirements&#xD;
                  (including those outlined in section 5.5) for the duration of the study and to&#xD;
                  report any changes in health status or medications, adverse event symptoms, or&#xD;
                  reactions immediately.&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               -  Individuals diagnosed with known allergies to facial or general skincare&#xD;
                  products.&#xD;
&#xD;
               -  Individuals who have the presence of an active systemic or local skin disease&#xD;
                  that may affect wound healing.&#xD;
&#xD;
               -  Individuals who have severe solar elastosis.&#xD;
&#xD;
               -  Individuals with sensitivity to topical lidocaine.&#xD;
&#xD;
               -  Individuals who have physical or psychological conditions unacceptable to the&#xD;
                  Investigator.&#xD;
&#xD;
               -  Individuals who have a recent history of significant trauma to the areas to be&#xD;
                  treated (&lt; 6 months).&#xD;
&#xD;
               -  Individuals who have significant scarring, other than acne scars, in the area(s)&#xD;
                  to be treated.&#xD;
&#xD;
               -  Individuals who have severe or cystic active and clinically significant acne on&#xD;
                  the area(s) to be treated. Clinically significant acne is defined as a subject&#xD;
                  who has &gt; 5 active inflammatory acne lesions (including acne conglobate, nodules,&#xD;
                  or cysts) in either the right or left treatment area.&#xD;
&#xD;
               -  Individuals who have a recent or current history of inflammatory skin disease,&#xD;
                  infection, cancerous/pre-cancerous lesion, unhealed wound or clinically&#xD;
                  significant acne in the proposed treatment areas. Individuals who have a history&#xD;
                  of systemic granulomatous diseases, active or inactive, (e.g. Sarcoid, Wegeners,&#xD;
                  TB, etc.) or connective tissue diseases (e.g. lupus, dermatomyositis, etc.).&#xD;
&#xD;
               -  Individuals who currently have or have a history of hypertrophic scars or keloid&#xD;
                  scars.&#xD;
&#xD;
               -  Individuals who currently have cancerous or pre-cancerous lesions in the areas to&#xD;
                  be treated and/or with a history of skin cancer.&#xD;
&#xD;
               -  Individuals who have the inability to understand instructions or to give informed&#xD;
                  consent.&#xD;
&#xD;
               -  Individuals who have had microdermabrasion or glycolic acid treatment to the&#xD;
                  treatment area(s) within 1 month prior to study participation or who will have&#xD;
                  this treatment during the study.&#xD;
&#xD;
               -  Individuals who have a history of chronic drug or alcohol abuse.&#xD;
&#xD;
               -  Individuals undergoing concurrent therapy that, in the Investigator's opinion,&#xD;
                  would interfere with the evaluation of the safety or efficacy of the study&#xD;
                  device.&#xD;
&#xD;
               -  Individuals who, in the Investigator's opinion, have a history of poor&#xD;
                  cooperation, noncompliance with medical treatment, or unreliability.&#xD;
&#xD;
               -  Individuals who are current smokers or have smoked in the last 5 years.&#xD;
&#xD;
               -  Individuals who have a history of the following cosmetic treatments in the&#xD;
                  area(s) to be treated:&#xD;
&#xD;
                    -  Skin tightening procedure within the past year;&#xD;
&#xD;
                    -  Injectable filler of any type within the past:&#xD;
&#xD;
                         -  12 months for Hyaluronic acid fillers (e.g. Restylane)&#xD;
&#xD;
                         -  12 months for Ca Hydroxyapatite fillers (e.g. Radiesse)&#xD;
&#xD;
                         -  24 months for Poly-L-Lactic acid fillers (e.g. Sculptra)&#xD;
&#xD;
                         -  Ever for permanent fillers (e.g. Silicone, ArteFill)&#xD;
&#xD;
                    -  Neurotoxins within the past 3 months;&#xD;
&#xD;
                    -  Ablative resurfacing laser treatment;&#xD;
&#xD;
                    -  Non-ablative, rejuvenating laser or light treatment within the past 6&#xD;
                       months;&#xD;
&#xD;
                    -  Surgical dermabrasion or deep facial peels;&#xD;
&#xD;
                    -  Had a chemical peel, dermabrasion, non-ablative laser, or fractional laser&#xD;
                       resurfacing of the neck within 4 weeks&#xD;
&#xD;
               -  Individuals with a history of using the following prescription medications:&#xD;
&#xD;
                    -  Accutane or other systemic retinoids within the past 6 months;&#xD;
&#xD;
                    -  Topical Retinoids within the past 2 weeks;&#xD;
&#xD;
                    -  Prescription-strength skin lightening devices (e.g. hydroquinone, tretinoin,&#xD;
                       AHA, BHA and polyhydroxy acids, 4-hydroxyanisole alone or in combination&#xD;
                       with tretinoin, etc.) within 4 months;&#xD;
&#xD;
                    -  Any anti-wrinkle, skin lightening devices, or any other device or topical or&#xD;
                       systemic medication is known to affect skin aging or dyschromia (devices&#xD;
                       containing alpha/beta/poly-hydroxy acids, vitamin C, soy, Q-10,&#xD;
                       hydroquinone; systemic or licorice extract (topically), Tego® Cosmo C250,&#xD;
                       Giga white, lemon juice extract (topically), Emblica extract, etc.) within 2&#xD;
                       weeks;&#xD;
&#xD;
                    -  Antiplatelet agents/Anticoagulants (Coumadin, Heparin, Plavix, chronic NSAID&#xD;
                       use); and/or&#xD;
&#xD;
                    -  Psychiatric drugs that in the Investigator's opinion would impair the&#xD;
                       subject from understanding the protocol requirements or understanding and&#xD;
                       signing the informed consent.&#xD;
&#xD;
               -  Individuals who are nursing, pregnant, or planning to become pregnant during the&#xD;
                  study according to the subject self-report.&#xD;
&#xD;
               -  Individuals having a health condition and/or pre-existing or dormant dermatologic&#xD;
                  disease on the face or body (e.g., psoriasis, rosacea, eczema, seborrheic&#xD;
                  dermatitis, vitiligo, hyper or hypo-skin pigmentation conditions such as&#xD;
                  post-inflammatory hyperpigmentation) that the Investigator or designee deems&#xD;
                  inappropriate for participation or could interfere with the outcome of the study.&#xD;
&#xD;
               -  Individuals with a history of immunosuppression/immune deficiency disorders&#xD;
                  (including HIV infection or AIDS) or currently using immunosuppressive&#xD;
                  medications (e.g., azathioprine, belimumab, cyclophosphamide, Enbrel, Imuran,&#xD;
                  Humira, mycophenolate mofetil, methotrexate, prednisone, Remicade, Stelara.)&#xD;
                  and/or radiation as determined by study documentation.&#xD;
&#xD;
               -  Individuals with uncontrolled diseases such as asthma, diabetes, hyperthyroidism,&#xD;
                  medically significant hypertension or hypothyroidism. Individuals having multiple&#xD;
                  health conditions may be excluded from participation even if the conditions are&#xD;
                  controlled by diet, medication, etc.&#xD;
&#xD;
               -  Individuals with any planned surgeries, overnight hospitalization, and/or&#xD;
                  invasive medical procedures during the course of the study.&#xD;
&#xD;
               -  Individuals who are currently participating in any other study involving the use&#xD;
                  of investigational devices or drugs or have participated in any clinical trial at&#xD;
                  UT Southwestern or at another research facility or doctor's office within 4 weeks&#xD;
                  prior to inclusion into the study.&#xD;
&#xD;
               -  Individuals who have an observable suntan, nevi, excessive hair, etc. or other&#xD;
                  dermal conditions on the neck that might influence the test results in the&#xD;
                  opinion of the Investigator or designee.&#xD;
&#xD;
               -  Individuals who have any condition, which in the opinion of the Investigator&#xD;
                  makes the patient unable to complete the study per protocol (e.g. patients not&#xD;
                  likely to avoid other facial cosmetic treatments; patients not likely to stay in&#xD;
                  the study for its duration because of other commitments, concomitant conditions,&#xD;
                  or past history; patients anticipated to be unreliable, or patients who have a&#xD;
                  concomitant condition that may develop symptoms that might confuse or confound&#xD;
                  study treatments or assessments).&#xD;
&#xD;
               -  Individuals who started hormone replacement therapies (HRT) or hormones for birth&#xD;
                  control less than 3 months prior to study entry or who plan on starting,&#xD;
                  stopping, or changing doses of HRT or hormones for birth control during the&#xD;
                  study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey Kenkel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Southwestern Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <results_first_submitted>July 6, 2021</results_first_submitted>
  <results_first_submitted_qc>November 3, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 1, 2021</results_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT03803059/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Pre-screening was conducted by phone to determine eligibility criteria through an IRB-approved script. Followed by in-clinic screening visits conducted between</recruitment_details>
      <pre_assignment_details>Only participants who met eligibility requirements were enrolled into the study.&#xD;
The subjects were given Pre-study instructions that include wash out Period: No topical medications or topical retinoids 2 weeks prior to visit 1.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Skinpen Precision System</title>
          <description>Microneedle treatment to neck areas using SkinPen Precision system which includes: Surgical instrument motors and accessories/attachments/Hydrogel&#xD;
A total of 32 subjects completed study participation.&#xD;
At visit 1 (baseline), subjects were screened for eligibility criteria and those who qualified either completed day 1 procedures at the same visit or returned to the clinic up to 14 days after visit 1 to complete day 1 procedures at visit 2.&#xD;
On days 1, 30, 60, and 90, after completion of visit assessments, doctors or fellows at the testing facility (henceforth referred to as &quot;clinic&quot;) treated each subject's fine lines and wrinkles, on the neck with SkinPen Precision System at depths of up to 2.5mm. Each subject's treatment depth was recorded. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.&#xD;
During the treatment period (days 1-90), subjects used the supporting materials[SKINFUSE® Purify Cleansing Complex, Reclaim Hydrating Support (Moisturizer), and Shield Zinc Oxide Sunscreen] as directed.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>At visit 1 (baseline), subjects were screened for eligibility criteria and those who qualified either completed day 1 procedures at the same visit or returned to the clinic up to 14 days after visit 1 to complete day 1 procedures at visit 2.&#xD;
35 Subjects were analyzed using the Fitzpatrick wrinkle scale and their scores are recorded.</population>
      <group_list>
        <group group_id="B1">
          <title>SkinPen Precision System</title>
          <description>Microneedle treatment to neck areas using SkinPen Precision system: Surgical instrument motors and accessories/attachments/Hydrogel.&#xD;
At visit 1 (baseline), subjects were screened for eligibility criteria and those who qualified either completed day 1 procedures at the same visit or returned to the clinic up to 14 days after visit 1 to complete day 1 procedures at visit 2.&#xD;
On days 1, 30, 60, and 90, after completion of visit assessments, doctors or fellows at the testing facility (henceforth referred to as &quot;clinic&quot;) treated each subject's fine lines and wrinkles, on the neck with SkinPen Precision System at depths of up to 2.5mm. Each subject's treatment depth was recorded. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.&#xD;
During the treatment period (days 1-90), subjects used the supporting materials[SKINFUSE® Purify Cleansing Complex, Reclaim Hydrating Support (Moisturizer), and Shield Zinc Oxide Sunscreen] as directed.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="35"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Individuals deemed to have fine lines and wrinkles by the Investigator and that desire correction of their fine lines and wrinkles</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fitzpatrick Skin Classification</title>
          <description>The Fitzpatrick skin classification is based on the skin's unprotected response to the first 30 to 45 minutes of sun exposure after a winter season without sun exposure. The categories of skin types are as follows:&#xD;
I-White, Always burns easily; never tans II-White, Always burns easily; tans minimally III-Cream white; Burns moderately; tans gradually IV-Brown; Mediterranean white skin. Burns minimally; always tans well V-Dark Brown; mid-eastern skin types, Rarely burns; tans profusely VI-Black; Never burns; deeply pigmented</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>l</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ll</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>lll</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>lV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>V</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Assessment of Wrinkle Severity Using the Lemperle Wrinkle Assessment Scale</title>
        <description>Wrinkling in the neck region will be assessed according to the following definitions:&#xD;
Class 0: No Wrinkles Class 1: Just perceptible wrinkle Class 2: Shallow wrinkles Class 3: Moderately deep wrinkle Class 4: Deep wrinkle, well-defined edges Class 5: Very deep wrinkle, redundant fold</description>
        <time_frame>Day 1 and 3 Month Post Treatment</time_frame>
        <population>Analysis population includes all participants completing the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of Wrinkle Severity Using the Lemperle Wrinkle Assessment Scale</title>
          <description>Wrinkling in the neck region will be assessed according to the following definitions:&#xD;
Class 0: No Wrinkles Class 1: Just perceptible wrinkle Class 2: Shallow wrinkles Class 3: Moderately deep wrinkle Class 4: Deep wrinkle, well-defined edges Class 5: Very deep wrinkle, redundant fold</description>
          <population>Analysis population includes all participants completing the study.</population>
          <units>Score on a Scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.31" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.45" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using Wilcoxon signed rank test. Testing hypothesis is that the mean change from baseline is zero</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Clinician's Global Aesthetic Improvement Assessment (CGAIS)</title>
        <description>This scale is completed in two steps:&#xD;
Based on a live assessment of the subject while referring to the subject's pre-treatment photographs of the neck, and&#xD;
Based on a comparison of the subject's pre-treatment photographs to the current post-treatment photographs of the neck.&#xD;
Rating and its Description&#xD;
1 --Very Much Improved: Optimal cosmetic result in this subject. 2--Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal for this subject.&#xD;
3-Improved: Obvious improvement in appearance from the initial condition, but re-treatment is indicated.&#xD;
4--No Change: The appearance is essentially the same as the original condition. 5--Worse: The appearance is worse than the original condition.</description>
        <time_frame>3 Month Post Treatment</time_frame>
        <population>The analysis population includes all participants completing the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinician's Global Aesthetic Improvement Assessment (CGAIS)</title>
          <description>This scale is completed in two steps:&#xD;
Based on a live assessment of the subject while referring to the subject's pre-treatment photographs of the neck, and&#xD;
Based on a comparison of the subject's pre-treatment photographs to the current post-treatment photographs of the neck.&#xD;
Rating and its Description&#xD;
1 --Very Much Improved: Optimal cosmetic result in this subject. 2--Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal for this subject.&#xD;
3-Improved: Obvious improvement in appearance from the initial condition, but re-treatment is indicated.&#xD;
4--No Change: The appearance is essentially the same as the original condition. 5--Worse: The appearance is worse than the original condition.</description>
          <population>The analysis population includes all participants completing the study.</population>
          <units>Score on a Scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.06" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using Wilcoxon signed rank test. Testing hypothesis is that the mean score is equal to 4 (no change).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject Global Aesthetic Improvement Scale (SGAIS)</title>
        <description>Rating and Description&#xD;
-Very Much Improved: Optimal cosmetic result.&#xD;
-Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal.&#xD;
-Improved: Obvious improvement in appearance from the initial condition.&#xD;
-No Change: The appearance is essentially the same as the original condition.&#xD;
-Worse: The appearance is worse than the original condition</description>
        <time_frame>1 Month Post Treatment and 3 Month Post Treatment</time_frame>
        <population>Analysis Population includes all participants completing the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Global Aesthetic Improvement Scale (SGAIS)</title>
          <description>Rating and Description&#xD;
-Very Much Improved: Optimal cosmetic result.&#xD;
-Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal.&#xD;
-Improved: Obvious improvement in appearance from the initial condition.&#xD;
-No Change: The appearance is essentially the same as the original condition.&#xD;
-Worse: The appearance is worse than the original condition</description>
          <population>Analysis Population includes all participants completing the study.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.90" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.16" spread="0.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using the Wilcoxon signed rank test. Testing hypothesis is that the mean score is equal to 4.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Transepidermal Water Loss of the Left Neck by Biox Aquaflux</title>
        <description>The severity of wrinkles is more due to increased UV exposure through the driver's side window on the left side of the face and neck, due to this reason, the Principal investigator performed the TEWL on the left side of the neck. This test was pre-specified in the protocol. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
Biox Aquaflux is used to measure transepidermal water loss (TEWL) measurements which evaluate barrier function of the skin epidermal layer to determine the progress of epidermal healing after treatment.&#xD;
Day 1 will be used as a baseline to analyze the change from baseline. TEWL is measured in g/m2/h. Normal rates of TEWL - from 2.3 g/m2/h to 44 g/m2/h - are compromised due to injury, infection, and/or severe damage as in the case of burns A decrease inTEWL reflects less water loss and an improvement in the skin's barrier properties; an absence of a change in treate</description>
        <time_frame>Baseline, 3 Months post treatment</time_frame>
        <population>Analysis population description includes all participants completing this test.</population>
        <group_list>
          <group group_id="O1">
            <title>SkinPen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Transepidermal Water Loss of the Left Neck by Biox Aquaflux</title>
          <description>The severity of wrinkles is more due to increased UV exposure through the driver's side window on the left side of the face and neck, due to this reason, the Principal investigator performed the TEWL on the left side of the neck. This test was pre-specified in the protocol. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
Biox Aquaflux is used to measure transepidermal water loss (TEWL) measurements which evaluate barrier function of the skin epidermal layer to determine the progress of epidermal healing after treatment.&#xD;
Day 1 will be used as a baseline to analyze the change from baseline. TEWL is measured in g/m2/h. Normal rates of TEWL - from 2.3 g/m2/h to 44 g/m2/h - are compromised due to injury, infection, and/or severe damage as in the case of burns A decrease inTEWL reflects less water loss and an improvement in the skin's barrier properties; an absence of a change in treate</description>
          <population>Analysis population description includes all participants completing this test.</population>
          <units>g/m2/h</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.56" spread="6.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 Month post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.62" spread="11.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using paired t-test. The testing hypothesis is that the mean change from baseline is zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.051</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vascular Density Measurements by Optical Coherence Tomography(OCT)</title>
        <description>Vivosight, an Optical coherence tomography (OCT) device, is used to non-invasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. OCT measurements of the vascular density are reported in percentage (%) and were performed on the neck at 100 microns, 200 microns, and 500 microns. Scores multiplied by 1000 for analysis.&#xD;
An increase in value indicates an increase in thickness and vascular density and skin tissue density.</description>
        <time_frame>Baseline (Day 1) and 3-Month post Treatment</time_frame>
        <population>Analysis population includes everyone completing measurements art Baseline and 3 months post-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Vascular Density Measurements by Optical Coherence Tomography(OCT)</title>
          <description>Vivosight, an Optical coherence tomography (OCT) device, is used to non-invasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. OCT measurements of the vascular density are reported in percentage (%) and were performed on the neck at 100 microns, 200 microns, and 500 microns. Scores multiplied by 1000 for analysis.&#xD;
An increase in value indicates an increase in thickness and vascular density and skin tissue density.</description>
          <population>Analysis population includes everyone completing measurements art Baseline and 3 months post-treatment.</population>
          <units>% VD (Vascular Density)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>OTC Measure at 100 microns- Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.66" spread="19.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OTC measure at 100 microns- 3 Month post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.56" spread="55.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OTC measure at 200 Microns- Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.45" spread="39.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OTC measure at 200 Microns- 3 month Post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.06" spread="56.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OTC measure at 500 Microns- Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.81" spread="39.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OTC measure at 500 Microns- 3 month Post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.07" spread="40.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated from paired t-test. The testing hypothesis is that the mean change from baseline is zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Skin Roughness Measurements by Optical Coherence Tomography(OCT)</title>
        <description>Vivosight, an optical coherence tomography (OCT) device, was used to noninvasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. Roughness measurements were calculated from the histologic images using RA and RZ. Skin roughness is measured in micro-meters.&#xD;
Ra is the average roughness of a surface. Rz is the difference between the tallest &quot;peak&quot; and the deepest &quot;valley&quot; on the surface.&#xD;
A decrease in value indicates a decrease in skin roughness when Baseline and 3 months post-treatment are compared.</description>
        <time_frame>Baseline (Day 1) and 3 Months post treatment</time_frame>
        <population>The analysis population includes participants finishing this assessment at day 1 and 3 months post-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Skin Roughness Measurements by Optical Coherence Tomography(OCT)</title>
          <description>Vivosight, an optical coherence tomography (OCT) device, was used to noninvasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. Roughness measurements were calculated from the histologic images using RA and RZ. Skin roughness is measured in micro-meters.&#xD;
Ra is the average roughness of a surface. Rz is the difference between the tallest &quot;peak&quot; and the deepest &quot;valley&quot; on the surface.&#xD;
A decrease in value indicates a decrease in skin roughness when Baseline and 3 months post-treatment are compared.</description>
          <population>The analysis population includes participants finishing this assessment at day 1 and 3 months post-treatment.</population>
          <units>micro-meters</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>RA-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RA-3 month post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RZ-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RZ- 3 Month Post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated from paired t-test. The testing hypothesis is that the mean change from baseline is zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.331</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>BTC 2000 Measurements- Energy Absorption</title>
        <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure energy absorption of the skin.&#xD;
The units for these measurements are Energy absorption - mmHg*mm&#xD;
Decrease in values for energy absorption will be seen as Improvement</description>
        <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
        <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>BTC 2000 Measurements- Energy Absorption</title>
          <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure energy absorption of the skin.&#xD;
The units for these measurements are Energy absorption - mmHg*mm&#xD;
Decrease in values for energy absorption will be seen as Improvement</description>
          <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
          <units>mmHg*mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Energy absorption-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.78" spread="59.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Energy absorption- 3 Month post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.68" spread="65.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using the paired t test. Testing hypothesis is that the mean change from baseline is zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.863</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>BTC 2000 Measurements for Skin Elasticity</title>
        <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure Elasticity values of the skin.&#xD;
The units for these measurements are in % of the distance traveled in µm.&#xD;
A decrease case in values for elasticity will be seen as an improvement after the treatments.</description>
        <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
        <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>BTC 2000 Measurements for Skin Elasticity</title>
          <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure Elasticity values of the skin.&#xD;
The units for these measurements are in % of the distance traveled in µm.&#xD;
A decrease case in values for elasticity will be seen as an improvement after the treatments.</description>
          <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
          <units>% of distance traveled in µm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Elasticity-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.09" spread="0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Elasticity- 3 month post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.33" spread="10.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using the paired t-test. The testing hypothesis is that the mean change from baseline is zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.048</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>BTC 2000 Measurements for Skin Deformations</title>
        <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure viscoelastic deformation, elastic deformation, and ultimate deformation values of the skin.&#xD;
The units for these measurements are in mm.&#xD;
A Decrease in values for these deformations will be seen as an Improvement.</description>
        <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
        <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>BTC 2000 Measurements for Skin Deformations</title>
          <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used to measure viscoelastic deformation, elastic deformation, and ultimate deformation values of the skin.&#xD;
The units for these measurements are in mm.&#xD;
A Decrease in values for these deformations will be seen as an Improvement.</description>
          <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Viscoelastic Deformation- Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.15" spread="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Viscoelastic Deformation- 3 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.16" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Elastic Deformation- Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.44" spread="0.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Elastic Deformation- 3 Month post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.41" spread="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ultimate Deformation-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.59" spread="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ultimate Deformation- 3 Month post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.57" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using the paired t-test. The testing hypothesis is that the mean change from baseline is zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.355</p_value>
            <p_value_desc>P-value reported is for viscoelastic deformation.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>at significance level alpha+0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>BTC 2000 Measurements for Stiffness</title>
        <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used for stiffness. Stiffness is measure in mmHg/mm and an increase in values of BTC measurements for stiffness would be seen as an improvement upon treatment.</description>
        <time_frame>Baseline (Day 1) and 3 month post treatment</time_frame>
        <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>BTC 2000 Measurements for Stiffness</title>
          <description>BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg &amp; mbar)&#xD;
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.&#xD;
BTC 2000 was used for stiffness. Stiffness is measure in mmHg/mm and an increase in values of BTC measurements for stiffness would be seen as an improvement upon treatment.</description>
          <population>Analysis population includes all participants completing this assessment on day 1 and 3 month post treatment.</population>
          <units>mmHg/mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stiffness- Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165.24" spread="65.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stiffness- 3 Month Post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="172.21" spread="65.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Calculated using the paired t test. Testing hypothesis is that the mean change from baseline is zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.859</p_value>
            <p_value_desc>Calculated with a paired T test. Testing hypothesis is that the mean change from baseline is zero.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Satisfaction Questionnaires</title>
        <description>Subjects completed a Sponsor-provided questionnaire regarding improvement in wrinkles, satisfaction with the treatment, and willingness to recommend the treatment to friends and family members</description>
        <time_frame>1 month post treatment</time_frame>
        <population>All</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Satisfaction Questionnaires</title>
          <description>Subjects completed a Sponsor-provided questionnaire regarding improvement in wrinkles, satisfaction with the treatment, and willingness to recommend the treatment to friends and family members</description>
          <population>All</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Do you notice any improvement in how your wrinkles look in the treated area?</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reduction in the number of wrinkles</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reduction in the size of wrinkles</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reduction in Pore Size</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clearer skin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoother skin texture</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>More even skin tone (color)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Would you recommend this treatment to your friends and family</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes- 1 Month post treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No-1 Month post Treatment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Patient satisfaction questionnaires were tabulated, and the frequency and percentage of all response options were reported for each question and time point calculated from the binomial (sign) test. The testing hypothesis is that the proportion of favorable responses is equal to the unfavorable</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>.A binomial (sign) test was performed to test if the the proportion of the combined designated favorable evaluations/responses is equal to the combined designated negative evaluations/responses for each question</non_inferiority_desc>
            <p_value>&lt;0.01</p_value>
            <method>Sign test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ultrasound Measurements</title>
        <description>Ultrasound measurements were performed using a 75 MHz ultrasonic transducer interfaced to a DUB 6100 OEM System (Taberna Pro Medicum, Lüneburg, Germany). Density and skin thickness measurements were obtained from the scans and increases in these values suggest a thickening of the epidermal and dermal tissue.</description>
        <time_frame>Day 1, 3 Months post treatment.</time_frame>
        <population>The analysis population includes all participants completing this assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Skinpen Precision System</title>
            <description>The subject's Fine lines and wrinkles were treated with the skinpen precision system at depths of 2.5mm. The hydrogel was used in conjunction with the treatment to protect against abrasion and friction during the procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Ultrasound Measurements</title>
          <description>Ultrasound measurements were performed using a 75 MHz ultrasonic transducer interfaced to a DUB 6100 OEM System (Taberna Pro Medicum, Lüneburg, Germany). Density and skin thickness measurements were obtained from the scans and increases in these values suggest a thickening of the epidermal and dermal tissue.</description>
          <population>The analysis population includes all participants completing this assessment.</population>
          <units>micro meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Epidermal thickeness-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.97" spread="52.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Epidermal thickness-3 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.46" spread="26.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Epidermal Density-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.74" spread="23.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Epidermal Density-3 M onth post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.46" spread="24.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermis Thickness-Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1034.83" spread="247.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermis Thickness- 3 Month Post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1092.08" spread="189.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermis Density- Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.87" spread="13.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermis Density- 3 Month Post treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.99" spread="15.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis that the mean change from baseline is zero was tested using a paired t-test</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.031</p_value>
            <p_value_desc>All statistical tests were 2-sided at significance level alpha=0.05. No multiple testing corrections were considered in the study.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The adverse event data were collected from Baseline up to 6 months post treatment.</time_frame>
      <desc>An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation where a subject is administered any product or medical device, regardless of a causal relationship with the test article</desc>
      <group_list>
        <group group_id="E1">
          <title>Skinpen Precision System</title>
          <description>Microneedle treatment to neck areas.&#xD;
SkinPen Precision: Surgical instrument motors and accessories/attachments/Hydrogel</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Root canal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Meniscus repair</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Viral Bronchitis</sub_title>
                <description>Subject was in Follow up (not receiving treatment) when the AE was reported to the testing facility.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast Cancer</sub_title>
                <description>Subject was in Follow up (not receiving treatment) when the AE was reported to the testing facility.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep Apnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney Stone removal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Biopsy on Jawline</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Afib Cardioversion</sub_title>
                <description>Subject was in Follow up (not receiving treatment) when the AE was reported to the testing facility.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Thomas Hitchcock, PhD.</name_or_title>
      <organization>Crown Laboratories, Inc</organization>
      <phone>8883723982</phone>
      <email>THitchcock@crownlaboratories.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03803059
org study id: Bellmed002
nct id: NCT03803059
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: Yes
This single-center, the clinical trial is being conducted over the course of 90 days followed
      by 1-month and 6-month post-treatment visits in order to assess the efficacy and tolerability
      of the Sponsor's SkinPen device when used by men and women with the wrinkles of the neck.
A total of 32 subjects completed study participation.

      At visit 1 (baseline), subjects were screened for eligibility criteria, and those who
      qualified either completed day 1 procedures at the same visit or returned to the clinic up to
      14 days after visit 1 to complete day 1 procedures at visit 2.

      On days 1, 30, 60, and 90, after completion of visit assessments, doctors or fellows at the
      testing facility (henceforth referred to as "clinic") treated each subject's wrinkles of the
      neck with SkinPen Precision System at depths of up to 2.5mm.

      During the post-treatment period, Clinical evaluations were conducted at visit 2 (day 1),
      visit 3 (day 30), visit 4 (day 60), visit 5 (day 90), visit 6 (1month post-treatment), and
      visit 7 (3 months post-treatment)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assessment of Wrinkle Severity Using the Lemperle Wrinkle Assessment Scale
time frame: Day 1 and 3 Month Post Treatment
description: Wrinkling in the neck region will be assessed according to the following definitions:
Class 0: No Wrinkles Class 1: Just perceptible wrinkle Class 2: Shallow wrinkles Class 3: Moderately deep wrinkle Class 4: Deep wrinkle, well-defined edges Class 5: Very deep wrinkle, redundant fold
measure: Clinician's Global Aesthetic Improvement Assessment (CGAIS)
time frame: 3 Month Post Treatment
description: This scale is completed in two steps:
Based on a live assessment of the subject while referring to the subject's pre-treatment photographs of the neck, and
Based on a comparison of the subject's pre-treatment photographs to the current post-treatment photographs of the neck.
Rating and its Description
1 --Very Much Improved: Optimal cosmetic result in this subject. 2--Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal for this subject.
3-Improved: Obvious improvement in appearance from the initial condition, but re-treatment is indicated.
4--No Change: The appearance is essentially the same as the original condition. 5--Worse: The appearance is worse than the original condition.
measure: Subject Global Aesthetic Improvement Scale (SGAIS)
time frame: 1 Month Post Treatment and 3 Month Post Treatment
description: Rating and Description
-Very Much Improved: Optimal cosmetic result.
-Much Improved: Marked improvement in appearance from the initial condition, but not completely optimal.
-Improved: Obvious improvement in appearance from the initial condition.
-No Change: The appearance is essentially the same as the original condition.
-Worse: The appearance is worse than the original condition
measure: Transepidermal Water Loss of the Left Neck by Biox Aquaflux
time frame: Baseline, 3 Months post treatment
description: The severity of wrinkles is more due to increased UV exposure through the driver's side window on the left side of the face and neck, due to this reason, the Principal investigator performed the TEWL on the left side of the neck. This test was pre-specified in the protocol. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.
Biox Aquaflux is used to measure transepidermal water loss (TEWL) measurements which evaluate barrier function of the skin epidermal layer to determine the progress of epidermal healing after treatment.
Day 1 will be used as a baseline to analyze the change from baseline. TEWL is measured in g/m2/h. Normal rates of TEWL - from 2.3 g/m2/h to 44 g/m2/h - are compromised due to injury, infection, and/or severe damage as in the case of burns A decrease inTEWL reflects less water loss and an improvement in the skin's barrier properties; an absence of a change in treate
measure: Vascular Density Measurements by Optical Coherence Tomography(OCT)
time frame: Baseline (Day 1) and 3-Month post Treatment
description: Vivosight, an Optical coherence tomography (OCT) device, is used to non-invasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. OCT measurements of the vascular density are reported in percentage (%) and were performed on the neck at 100 microns, 200 microns, and 500 microns. Scores multiplied by 1000 for analysis.
An increase in value indicates an increase in thickness and vascular density and skin tissue density.
measure: Skin Roughness Measurements by Optical Coherence Tomography(OCT)
time frame: Baseline (Day 1) and 3 Months post treatment
description: Vivosight, an optical coherence tomography (OCT) device, was used to noninvasively gather topographical and histologic images of pre-and post-treated skin. This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle. Roughness measurements were calculated from the histologic images using RA and RZ. Skin roughness is measured in micro-meters.
Ra is the average roughness of a surface. Rz is the difference between the tallest "peak" and the deepest "valley" on the surface.
A decrease in value indicates a decrease in skin roughness when Baseline and 3 months post-treatment are compared.
measure: BTC 2000 Measurements- Energy Absorption
time frame: Baseline (Day 1) and 3 month post treatment
description: BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg & mbar)
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.
BTC 2000 was used to measure energy absorption of the skin.
The units for these measurements are Energy absorption - mmHg*mm
Decrease in values for energy absorption will be seen as Improvement
measure: BTC 2000 Measurements for Skin Elasticity
time frame: Baseline (Day 1) and 3 month post treatment
description: BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg & mbar)
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.
BTC 2000 was used to measure Elasticity values of the skin.
The units for these measurements are in % of the distance traveled in µm.
A decrease case in values for elasticity will be seen as an improvement after the treatments.
measure: BTC 2000 Measurements for Skin Deformations
time frame: Baseline (Day 1) and 3 month post treatment
description: BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg & mbar)
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.
BTC 2000 was used to measure viscoelastic deformation, elastic deformation, and ultimate deformation values of the skin.
The units for these measurements are in mm.
A Decrease in values for these deformations will be seen as an Improvement.
measure: BTC 2000 Measurements for Stiffness
time frame: Baseline (Day 1) and 3 month post treatment
description: BTC-2000™ Features: High-Resolution Target Laser (µm) and negative pressure (mmHg & mbar)
This procedure was performed 4-6 cm from the left lateral neck along the sternocleidomastoid muscle.
BTC 2000 was used for stiffness. Stiffness is measure in mmHg/mm and an increase in values of BTC measurements for stiffness would be seen as an improvement upon treatment.
measure: Patient Satisfaction Questionnaires
time frame: 1 month post treatment
description: Subjects completed a Sponsor-provided questionnaire regarding improvement in wrinkles, satisfaction with the treatment, and willingness to recommend the treatment to friends and family members
measure: Ultrasound Measurements
time frame: Day 1, 3 Months post treatment.
description: Ultrasound measurements were performed using a 75 MHz ultrasonic transducer interfaced to a DUB 6100 OEM System (Taberna Pro Medicum, Lüneburg, Germany). Density and skin thickness measurements were obtained from the scans and increases in these values suggest a thickening of the epidermal and dermal tissue.
arm group label: Wrinkles of the Neck
arm group type: Experimental
description: Microneedle treatment neck areas.
intervention type: Device
intervention name: SkinPen Precision
description: Surgical instrument motors and accessories/attachments/Hydrogel
arm group label: Wrinkles of the Neck
criteria: 
gender: All
minimum age: 35 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeffrey Kenkel, MD
role: Principal Investigator
affiliation: University of Texas Southwestern Medical Center
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 