<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/NCT03259958</url>
  </required_header>
  <id_info>
    <org_study_id>P-16010</org_study_id>
    <nct_id>NCT03259958</nct_id>
  </id_info>
  <brief_title>A Bioequivalence Study of Corplex™ Donepezil Transdermal Delivery System Compared to Aricept®</brief_title>
  <official_title>A Study to Assess the Steady-State Bioequivalence of Once-Weekly Corplex™ 10mg Donepezil Transdermal Delivery System Compared to Daily Oral Administration of Aricept®</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Corium, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Corium, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A study to assess the steady-state bioequivalence of once-weekly Corplex™ Donepezil 10 mg&#xD;
      Transdermal Delivery System (TDS) compared to daily administration of Aricept®&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Open label, randomized, 2-period, multiple-dose crossover study.&#xD;
&#xD;
      Approximately 86 healthy, adult male and female subjects will be enrolled.&#xD;
&#xD;
      Subjects will be randomized to 1 of 2 treatment sequences prior to the first study product&#xD;
      treatment in treatment period 1.&#xD;
&#xD;
      For each treatment period; subjects will receive donepezil for 5 consecutive weeks. Blood&#xD;
      samples for donepezil PK will be collected pre-dose through week 10.&#xD;
&#xD;
      Adhesion and skin irritation will be monitored throughout TDS treatments. Safety will be&#xD;
      monitored throughout the study by adverse event reporting, repeated clinical and laboratory&#xD;
      evaluations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2017</start_date>
  <completion_date type="Actual">March 14, 2018</completion_date>
  <primary_completion_date type="Actual">March 13, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PK, AUC</measure>
    <time_frame>Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total</time_frame>
    <description>To assess the plasma concentration (AUC) of once-weekly Corplex Donepezil (TDS) compared to once-daily (QD) administration of Aricept (donepezil hydrochloride [HCl]).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK, Cmax</measure>
    <time_frame>Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total</time_frame>
    <description>To assess the maximum observed concentrations (Cmax) of once-weekly Corplex Donepezil (TDS) compared to once-daily (QD) administration of Aricept (donepezil hydrochloride [HCl]).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Daily during 5 week treatment period and during the 5 week follow-on period</time_frame>
    <description>General Safety (AE and SAE as reported by subject following guidance CTCAE v4.0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PI assessment of local skin irritation response to TDS</measure>
    <time_frame>0.5hr, 24hr, 48hr and 72hr after each TDS removal. (5 consecutive weeks)</time_frame>
    <description>To evaluate the safety and tolerability (including local skin irritation) of once-weekly Corplex Donepezil TDS. Dermal Response assessed using 8 point categorical scale. Other effects assessed using a 6 point scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PI assessment of TDS Adhesion</measure>
    <time_frame>Daily during 5 week treatment period</time_frame>
    <description>Adhesion data will be collected during each 7-day patch wear period throughout 5 week treatment period. Percent adherence will be assessed using 12 point categorical scale.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Donepezil TDS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Corplex Donepezil TDS 5 mg/day followed by Donepezil TDS 10mg/day applied weekly for 5 consecutive weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aricept</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Aricept 5 mg/day followed by Aricept 10 mg/day once daily for 5 consecutive weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donepezil TDS</intervention_name>
    <description>Donepezil Hydrochloride Transdermal Delivery System</description>
    <arm_group_label>Donepezil TDS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aricept</intervention_name>
    <description>Aricept Tablet</description>
    <arm_group_label>Aricept</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy, adult, male or female&#xD;
&#xD;
          -  Body mass index ≥ 18.0 and ≤ 32.0 kg/m2 at screening&#xD;
&#xD;
          -  Medically healthy with no clinically significant medical history, physical&#xD;
             examination, laboratory profiles, vital signs or electrocardiograms (ECGs), as deemed&#xD;
             by the Investigator&#xD;
&#xD;
          -  Have a Fitzpatrick skin type of I, II or III or have skin colorimeter scores&#xD;
             equivalent to the allowed Fitzpatrick skin type&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of hypersensitivity or idiosyncratic reaction to the study drugs&#xD;
             or related compounds (including piperidine derivatives and other cholinesterase&#xD;
             inhibitors)&#xD;
&#xD;
          -  Has intolerance to venipuncture and/or inability to comply with the extensive blood&#xD;
             sampling required for this study or does not have suitable veins in both arms&#xD;
&#xD;
          -  Potential for occupational exposure to anticholinesterase agents.&#xD;
&#xD;
          -  Female subjects with a positive pregnancy test or lactating&#xD;
&#xD;
          -  Positive urine drug or alcohol results&#xD;
&#xD;
          -  Estimated creatinine clearance in non-elderly subjects &lt;80 mL/min at screening and in&#xD;
             elderly subjects (i.e., ≥55 years of age) &lt;60 mL/min at screening&#xD;
&#xD;
          -  Hemoglobin value of less than 11.5 g/dl for females, 13.0 g/dl for males at screening&#xD;
             and first check-in&#xD;
&#xD;
          -  Any of the following drugs for 28 days prior to the first dose of study drug in&#xD;
             Treatment Period 1 and throughout the study:&#xD;
&#xD;
               -  significant inducers of cytochrome P450 (CYP) enzymes and/or P-glycoprotein;&#xD;
&#xD;
               -  anti-inflammatory drugs or cyclooxygenase 2 (COX-2) analgesic;&#xD;
&#xD;
               -  beta-blockers;&#xD;
&#xD;
               -  anti-fungal medications;&#xD;
&#xD;
               -  anti-histamines;&#xD;
&#xD;
               -  cholinergics and anti-cholinergics;&#xD;
&#xD;
               -  oral corticosteroids;&#xD;
&#xD;
               -  Prolia;&#xD;
&#xD;
               -  adjuvant analgesics&#xD;
&#xD;
          -  Muscle relaxants, anti-Parkinsonian or neuroleptic medications prior to the first dose&#xD;
             of study drug&#xD;
&#xD;
          -  History or presence of excessive hairy skin on application sites as deemed by the&#xD;
             Investigator to potentially interfere with drug absorption&#xD;
&#xD;
          -  History or presence of significant skin damage, diffuse skin diseases, scars, tattoos&#xD;
             on the application sites or other skin disturbances as deemed by the Investigator to&#xD;
             potentially interfere with drug absorption or irritation assessments&#xD;
&#xD;
          -  Use of donepezil hydrochloride or related drugs within 30 days prior to the first&#xD;
             study drug administration&#xD;
&#xD;
          -  Participation in another clinical study within 30 days prior to the first study drug&#xD;
             administration&#xD;
&#xD;
          -  Clinically significant depression symptoms or suicidal ideation or behavior as&#xD;
             determined by the Investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Danielle Armas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Celerion</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion Inc.</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>July 31, 2018</last_update_submitted>
  <last_update_submitted_qc>July 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2018</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>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Donepezil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No Plans</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03259958
org study id: P-16010
nct id: NCT03259958
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A study to assess the steady-state bioequivalence of once-weekly Corplex™ Donepezil 10 mg
      Transdermal Delivery System (TDS) compared to daily administration of Aricept®
Open label, randomized, 2-period, multiple-dose crossover study.

      Approximately 86 healthy, adult male and female subjects will be enrolled.

      Subjects will be randomized to 1 of 2 treatment sequences prior to the first study product
      treatment in treatment period 1.

      For each treatment period; subjects will receive donepezil for 5 consecutive weeks. Blood
      samples for donepezil PK will be collected pre-dose through week 10.

      Adhesion and skin irritation will be monitored throughout TDS treatments. Safety will be
      monitored throughout the study by adverse event reporting, repeated clinical and laboratory
      evaluations.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PK, AUC
time frame: Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total
description: To assess the plasma concentration (AUC) of once-weekly Corplex Donepezil (TDS) compared to once-daily (QD) administration of Aricept (donepezil hydrochloride [HCl]).
measure: PK, Cmax
time frame: Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total
description: To assess the maximum observed concentrations (Cmax) of once-weekly Corplex Donepezil (TDS) compared to once-daily (QD) administration of Aricept (donepezil hydrochloride [HCl]).
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Daily during 5 week treatment period and during the 5 week follow-on period
description: General Safety (AE and SAE as reported by subject following guidance CTCAE v4.0)
measure: PI assessment of local skin irritation response to TDS
time frame: 0.5hr, 24hr, 48hr and 72hr after each TDS removal. (5 consecutive weeks)
description: To evaluate the safety and tolerability (including local skin irritation) of once-weekly Corplex Donepezil TDS. Dermal Response assessed using 8 point categorical scale. Other effects assessed using a 6 point scale.
measure: PI assessment of TDS Adhesion
time frame: Daily during 5 week treatment period
description: Adhesion data will be collected during each 7-day patch wear period throughout 5 week treatment period. Percent adherence will be assessed using 12 point categorical scale.
arm group label: Donepezil TDS
arm group type: Experimental
description: Corplex Donepezil TDS 5 mg/day followed by Donepezil TDS 10mg/day applied weekly for 5 consecutive weeks
arm group label: Aricept
arm group type: Active Comparator
description: Aricept 5 mg/day followed by Aricept 10 mg/day once daily for 5 consecutive weeks
intervention type: Drug
intervention name: Donepezil TDS
description: Donepezil Hydrochloride Transdermal Delivery System
arm group label: Donepezil TDS
intervention type: Drug
intervention name: Aricept
description: Aricept Tablet
arm group label: Aricept
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Danielle Armas, MD
role: Principal Investigator
affiliation: Celerion
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Donepezil
sharing ipd: No
ipd description: No Plans