<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/NCT03297502</url>
  </required_header>
  <id_info>
    <org_study_id>SYM 2016-01</org_study_id>
    <nct_id>NCT03297502</nct_id>
  </id_info>
  <brief_title>Safety and Bioequivalence of Pimecrolimus Cream 1% and Elidel R in Treatment of Mild to Moderate Atopic Dermatitis</brief_title>
  <official_title>Multicenter Study of the Safety and Bioequivalence of Par's Pimecrolimus Cream, 1% and RLD Elidel® (Pimecrolimus Cream, 1%) and Compare Both Active Treatments to a Vehicle Control in Treatment of Mild to Moderate Atopic Dermatitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Par Pharmaceutical, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Par Pharmaceutical, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase 3, double-blind, randomized, parallel-group, placebo-controlled, multicenter study to&#xD;
      evaluate the safety and bioequivalence of Par Pharmaceutical Inc.'s Pimecrolimus Cream, 1%&#xD;
      and Reference Listed Elidel® (Pimecrolimus Cream, 1%). The study compares both active&#xD;
      treatments to a placebo control in the treatment of mild to moderate atopic dermatitis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2016</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of subjects with treatment success in each treatment group</measure>
    <time_frame>Day 15</time_frame>
    <description>Treatment success is defined as an Investigator's Global Assessment (IGA) Rating of &quot;clear&quot; or &quot;almost clear&quot; ( i.e., a score of 0 or 1 on a scale of 0 [clear] through 4. IGA Scale: 0 = Clear (minor discoloration, no erythema, induration, population, oozing/crusting. 1= Almost Clear (trace, faint erythema, almost no induration/population, no oozing/crusting. 2 = Mild (faint erythema, mild induration/population, no oozing/crusting. 3 = Moderate (Pink-red erythema, moderate induration/population, some oozing/crusting. 4 = Severe (Deep/bright erythema, severe induration/population, with oozing/crusting.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in severity (erythema)</measure>
    <time_frame>Baseline, Day 15</time_frame>
    <description>Change from baseline in severity in clinical signs and symptoms of erythema is assessed.&#xD;
0 = None: No erythema present&#xD;
= Mild: Slight erythema, very light-pink&#xD;
= Moderate: Dull red, clearly distinguishable&#xD;
= Severe: Deep/dark red</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in severity (induration/population)</measure>
    <time_frame>Baseline, Day 15</time_frame>
    <description>Change from baseline in severity in clinical signs and symptoms of induration/papulation is assessed.&#xD;
0 = None: No elevation&#xD;
= Mild: Slightly perceptible elevation&#xD;
= Moderate: Clearly perceptible elevation&#xD;
= Severe: Marked and extensive elevation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in severity (lichenification)</measure>
    <time_frame>Baseline, Day 15</time_frame>
    <description>Change from baseline in severity in clinical signs and symptoms of lichenification is assessed.&#xD;
0 = None: No lichenification&#xD;
= Mild: Slight thickening of the skin discernible only by touch and with skin markings minimally exaggerated&#xD;
= Moderate: Definite thickening of the skin with skin markings exaggerated so that they form a visible criss-cross pattern&#xD;
= Severe: Thickened indurated skin with skin markings visibly portraying an exaggerated criss-cross pattern</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in severity (pruritis)</measure>
    <time_frame>Baseline, Day 15</time_frame>
    <description>Change from baseline in severity in clinical signs and symptoms of puritus is assessed.&#xD;
0 = None: No itching&#xD;
= Mild: Occasional, slight itching/scratching&#xD;
= Moderate: Constant or intermittent itching/scratching/discomfort that is not disturbing sleep&#xD;
= Severe: Bothersome itching/scratching/discomfort that is disturbing sleep</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">582</enrollment>
  <condition>Atopic Dermatitis</condition>
  <arm_group>
    <arm_group_label>Pimecrolimus cream, 1%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Elidel (pimecrolimus) cream 1%</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pimecrolimus cream 1%</intervention_name>
    <arm_group_label>Pimecrolimus cream, 1%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Elidel (pimecrolimus) cream 1%</intervention_name>
    <arm_group_label>Elidel (pimecrolimus) cream 1%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent/assent for the study.&#xD;
&#xD;
          2. Non-immunocompromised male or female aged 12 years or older.&#xD;
&#xD;
          3. A clinical diagnosis of mild to moderate atopic dermatitis that has failed to respond&#xD;
             adequately to other topical prescription treatments for atopic dermatitis, or subjects&#xD;
             for whom the use of those other treatments is deemed inadvisable.&#xD;
&#xD;
          4. A diagnosis of atopic dermatitis for at least 3 months.&#xD;
&#xD;
          5. A baseline Investigator's Global Assessment (IGA) of disease severity of mild or&#xD;
             moderate (score of 2 or 3). (See Section 9.6.10 for the scale.)&#xD;
&#xD;
          6. An affected area of atopic dermatitis involvement of at least 5% of the body surface&#xD;
             area (BSA) at Visit 2/Day 1 (Baseline), as defined by the criteria of Hanifin and&#xD;
             Rajka (1980).&#xD;
&#xD;
          7. Treatment with a bland emollient for at least 7 days prior to Visit 2/Day 1&#xD;
             (Baseline).&#xD;
&#xD;
          8. Agree to adhere to protocol-specified requirements and concomitant therapy&#xD;
             restrictions.&#xD;
&#xD;
          9. Willing to avoid constant sun exposure and the use of tanning booths or other UV light&#xD;
             sources during participation in the study.&#xD;
&#xD;
         10. In general good health, non-immunocompromised, and free from any clinically&#xD;
             significant disease, other than atopic dermatitis, that might interfere with the study&#xD;
             evaluations.&#xD;
&#xD;
         11. Willing and able to understand and comply with the requirements of the study, apply&#xD;
             the study medication as instructed, return for the required study visits, comply with&#xD;
             therapy prohibitions, and complete the study.&#xD;
&#xD;
         12. Female subjects of childbearing potential (excluding women who are surgically&#xD;
             sterilized [hysterectomy, bilateral tubal ligation, or bilateral ovariectomy] or have&#xD;
             been postmenopausal for at least 1 year) must have a negative urine pregnancy test and&#xD;
             must be willing to use a medically accepted method of contraception during the study.&#xD;
             The following are considered acceptable methods of birth control for the purpose of&#xD;
             this study: oral contraceptives, contraceptive patches, contraceptive implant, vaginal&#xD;
             contraceptive, double barrier methods (e.g., condom and spermicide), contraceptive&#xD;
             injection (Depo-Provera®), intrauterine device (IUD), hormonal IUD (Mirena®), Essure®&#xD;
             permanent birth control, and abstinence with a documented second acceptable method of&#xD;
             birth control if the subject becomes sexually active.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Females who are pregnant, breastfeeding, intending to become pregnant during the&#xD;
             study, or who do not agree to use an acceptable form of birth control during the&#xD;
             study.&#xD;
&#xD;
          2. Active cutaneous bacterial or viral infection in any proposed treatment area at Visit&#xD;
             2/Baseline (e.g., clinically infected atopic dermatitis).&#xD;
&#xD;
          3. Sunburn, extensive scarring, or pigmented lesion(s) in any treatment area at Visit&#xD;
             2/Baseline that would interfere with the study evaluations.&#xD;
&#xD;
          4. History of confounding skin conditions, e.g., psoriasis, rosacea, erythroderma, or&#xD;
             ichthyosis.&#xD;
&#xD;
          5. History or presence of Netherton's Syndrome, immunological deficiencies or diseases,&#xD;
             HIV, diabetes, malignancy, serious active or recurrent infection, clinically&#xD;
             significant severe renal insufficiency, or severe hepatic disorders.&#xD;
&#xD;
          6. Use of any treatment listed in Table 9.1 more recently than the indicated washout&#xD;
             period prior to Visit 2/Baseline.&#xD;
&#xD;
          7. Need or intent to continue to use any treatment listed in Table 9.1 during the current&#xD;
             study.&#xD;
&#xD;
             Table 9.1 Medications, Supplements, and Other Substances Prohibited for Study Entry&#xD;
             Prohibited Medications, Supplements, and Other Substances Washout Period Prior to&#xD;
             Randomization Visit 2/Baseline&#xD;
&#xD;
               -  Systemic corticosteroids (oral and injectable [intravenous and intramuscular])&#xD;
                  (Intranasal and Inhalational steroids are allowed if use is kept constant during&#xD;
                  the study)&#xD;
&#xD;
               -  UVA/UVB therapy&#xD;
&#xD;
               -  PUVA (psoralen plus ultraviolet A) therapy&#xD;
&#xD;
               -  Tanning booths&#xD;
&#xD;
               -  Nonprescription UV light sources&#xD;
&#xD;
               -  Immunomodulators or immunosuppressive therapies&#xD;
&#xD;
               -  Interferon&#xD;
&#xD;
               -  Cytotoxic drugs (e.g., methotrexate, cyclophosphamide, azathioprine)&#xD;
&#xD;
               -  Oral retinoids&#xD;
&#xD;
               -  Systemic anti-fungals&#xD;
&#xD;
               -  Tacrolimus&#xD;
&#xD;
               -  Pimecrolimus 30 days (1 month)&#xD;
&#xD;
               -  Systemic antibiotics&#xD;
&#xD;
               -  Topical calcipotriene or other topical vitamin D preparations&#xD;
&#xD;
               -  Topical retinoids 14 days (2 weeks)&#xD;
&#xD;
               -  Topical and oral antihistamines&#xD;
&#xD;
               -  Topical antibiotics&#xD;
&#xD;
               -  Topical corticosteroids&#xD;
&#xD;
               -  Topical antifungals&#xD;
&#xD;
               -  Other topical drug products 7 days (1 week)&#xD;
&#xD;
               -  Any topical product (e.g., sunscreens, lotions, creams) in areas to be treated&#xD;
                  except for bland emollient (moisturizer)&#xD;
&#xD;
               -  Grapefruit or grapefruit juice which is considered a CYP3A inhibitor 24 hours&#xD;
&#xD;
          8. Current use of calcium channel blockers (e.g, amlodipine, nifedipine, verapamil,&#xD;
             diltiazem, felodipine, isradipine, nisoldipine, etc) and/or cimetidine (e.g., Tagamet)&#xD;
             which are CPY3A inhibitors.&#xD;
&#xD;
          9. Known allergy or hypersensitivity to pimecrolimus or any other component of the Test&#xD;
             or Reference product.&#xD;
&#xD;
         10. Unwilling to minimize or avoid natural and artificial sunlight exposure during&#xD;
             treatment.&#xD;
&#xD;
         11. Consumption of excessive alcohol, abuse of drugs, or a condition that could compromise&#xD;
             the subject's ability to comply with study requirements.&#xD;
&#xD;
         12. Any clinically significant condition or situation other than the condition being&#xD;
             studied that, in the opinion of the investigator, would interfere with the study&#xD;
             evaluations or optimal participation in the study.&#xD;
&#xD;
         13. Use of any investigational drug or investigational device within 30 days prior to&#xD;
             Visit 2/Baseline.&#xD;
&#xD;
         14. Previous participation in this study.&#xD;
&#xD;
         15. Employees of the research center or investigator.&#xD;
&#xD;
         16. Family members of employees of the research center or investigator.&#xD;
&#xD;
         17. Family members living in the same household participating at the same time.&#xD;
&#xD;
        Table 9.2 Medications (Prescription and Over-the-Counter), Supplements, and Other&#xD;
        Substances Prohibited During the Study Prohibited Medications, Supplements, and Other&#xD;
        Substances Treatment for atopic dermatitis other than assigned study medication or bland&#xD;
        emollient.&#xD;
&#xD;
        Topical or systemic (oral and injectable) corticosteroid (Intranasal and inhalational&#xD;
        steroids are allowed if kept constant during the study) Topical or systemic antibiotic&#xD;
        Topical or systemic antifungal Topical or oral antihistamine (e.g., diphenhydramine,&#xD;
        hydroxyzine) Immunosuppressive drugs Immunomodulator (e.g., tacrolimus) Calcipotriene or&#xD;
        other topical vitamin D preparations Topical or oral retinoids Interferon Cyclosporine&#xD;
        Methotrexate Azathioprine CPY3A inhibitor (e.g., erythromycin, itraconazole, ketoconazole,&#xD;
        fluconazole, calcium channel blockers, cimetidine, grapefruit or grapefruit juice) Topical&#xD;
        product other than assigned study medication or bland emollient (e.g., sunscreen, new brand&#xD;
        of cosmetic or cleanser, cream, lotion, ointment, or powder) applied on or near the&#xD;
        treatment area(s) Phototherapy (e.g., PUVA, UVA or UVB therapy)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew Davis, MD, RPh</last_name>
    <role>Study Director</role>
    <affiliation>Endo Pharmaceuticals</affiliation>
  </overall_official>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>September 28, 2017</last_update_submitted>
  <last_update_submitted_qc>September 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatitis, Atopic</mesh_term>
    <mesh_term>Dermatitis</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pimecrolimus</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03297502
org study id: SYM 2016-01
nct id: NCT03297502
lead sponsor: 
has dmc: No
A phase 3, double-blind, randomized, parallel-group, placebo-controlled, multicenter study to
      evaluate the safety and bioequivalence of Par Pharmaceutical Inc.'s Pimecrolimus Cream, 1%
      and Reference Listed Elidel® (Pimecrolimus Cream, 1%). The study compares both active
      treatments to a placebo control in the treatment of mild to moderate atopic dermatitis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of subjects with treatment success in each treatment group
time frame: Day 15
description: Treatment success is defined as an Investigator's Global Assessment (IGA) Rating of "clear" or "almost clear" ( i.e., a score of 0 or 1 on a scale of 0 [clear] through 4. IGA Scale: 0 = Clear (minor discoloration, no erythema, induration, population, oozing/crusting. 1= Almost Clear (trace, faint erythema, almost no induration/population, no oozing/crusting. 2 = Mild (faint erythema, mild induration/population, no oozing/crusting. 3 = Moderate (Pink-red erythema, moderate induration/population, some oozing/crusting. 4 = Severe (Deep/bright erythema, severe induration/population, with oozing/crusting.
measure: Change from baseline in severity (erythema)
time frame: Baseline, Day 15
description: Change from baseline in severity in clinical signs and symptoms of erythema is assessed.
0 = None: No erythema present
= Mild: Slight erythema, very light-pink
= Moderate: Dull red, clearly distinguishable
= Severe: Deep/dark red
measure: Change from baseline in severity (induration/population)
time frame: Baseline, Day 15
description: Change from baseline in severity in clinical signs and symptoms of induration/papulation is assessed.
0 = None: No elevation
= Mild: Slightly perceptible elevation
= Moderate: Clearly perceptible elevation
= Severe: Marked and extensive elevation
measure: Change from baseline in severity (lichenification)
time frame: Baseline, Day 15
description: Change from baseline in severity in clinical signs and symptoms of lichenification is assessed.
0 = None: No lichenification
= Mild: Slight thickening of the skin discernible only by touch and with skin markings minimally exaggerated
= Moderate: Definite thickening of the skin with skin markings exaggerated so that they form a visible criss-cross pattern
= Severe: Thickened indurated skin with skin markings visibly portraying an exaggerated criss-cross pattern
measure: Change from baseline in severity (pruritis)
time frame: Baseline, Day 15
description: Change from baseline in severity in clinical signs and symptoms of puritus is assessed.
0 = None: No itching
= Mild: Occasional, slight itching/scratching
= Moderate: Constant or intermittent itching/scratching/discomfort that is not disturbing sleep
= Severe: Bothersome itching/scratching/discomfort that is disturbing sleep
arm group label: Pimecrolimus cream, 1%
arm group type: Experimental
arm group label: Elidel (pimecrolimus) cream 1%
arm group type: Active Comparator
arm group label: placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: pimecrolimus cream 1%
arm group label: Pimecrolimus cream, 1%
intervention type: Drug
intervention name: Elidel (pimecrolimus) cream 1%
arm group label: Elidel (pimecrolimus) cream 1%
intervention type: Drug
intervention name: placebo
arm group label: placebo
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Matthew Davis, MD, RPh
role: Study Director
affiliation: Endo Pharmaceuticals
responsible party type: Sponsor
mesh term: Dermatitis, Atopic
mesh term: Dermatitis
mesh term: Eczema
mesh term: Pimecrolimus
mesh term: Tacrolimus