<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/NCT04462029</url>
  </required_header>
  <id_info>
    <org_study_id>BR-DPZ-CT-102</org_study_id>
    <nct_id>NCT04462029</nct_id>
  </id_info>
  <brief_title>A Study to Compare the Pharmacokinetics of BR4002 and BR4002-1 in Healthy Volunteers</brief_title>
  <official_title>A Randomized, Open-label, Single-dose, Crossover Study to Evaluate the Pharmacokinetics and Safety/Tolerability of BR4002 Comparing to BR4002-1 in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boryung Pharmaceutical Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boryung Pharmaceutical Co., Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed as a randomized, open-label, single-dose, 6x3 crossover study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 18 subjects will be randomized into 6 sequence groups. The investigational&#xD;
      products will be administered according to the treatment groups (R, T1, and T2) assigned to&#xD;
      each sequence group in Period 1, Period 2, and Period 3. In between each period, there will&#xD;
      be a washout period (28 days) long enough for the administered IP to be metabolized and&#xD;
      eliminated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 5, 2020</start_date>
  <completion_date type="Actual">October 7, 2020</completion_date>
  <primary_completion_date type="Actual">October 7, 2020</primary_completion_date>
  <phase>Early 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>Pharmacokinetic variables -Area Under the concentration-time Curve from time 0 to t after single dosing(AUCt) of BR4002 and BR4002-1</measure>
    <time_frame>0~240 hours after medication</time_frame>
    <description>PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic variables - maximum observed plasma concentration(Cmax) of BR4002 and BR4002-1</measure>
    <time_frame>0~240 hours after medication</time_frame>
    <description>PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic variables - Area Under the concentration-time Curve from time 0 to infinite after single dosing(AUCinf) of BR4002 and BR4002-1</measure>
    <time_frame>0~240 hours after medication</time_frame>
    <description>PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic variables - Time of occurrence of Cmax(Tmax) of BR4002 and BR4002-1</measure>
    <time_frame>0~240 hours after medication</time_frame>
    <description>PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Dementia Alzheimers</condition>
  <arm_group>
    <arm_group_label>sequence 1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.&#xD;
R(Reference): BR4002-1 (oral intake) 5mg single-dose&#xD;
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)&#xD;
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)&#xD;
sequence 1: R - T1 - T2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sequence 2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.&#xD;
R(Reference): BR4002-1 (oral intake) 5mg single-dose&#xD;
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)&#xD;
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)&#xD;
sequence 2: R - T2 - T1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sequence 3</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.&#xD;
R(Reference): BR4002-1 (oral intake) 5mg single-dose&#xD;
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)&#xD;
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)&#xD;
sequence 3: T1 - R - T2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sequence 4</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.&#xD;
R(Reference): BR4002-1 (oral intake) 5mg single-dose&#xD;
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)&#xD;
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)&#xD;
sequence 4: T1 - T2 - R</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sequence 5</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.&#xD;
R(Reference): BR4002-1 (oral intake) 5mg single-dose&#xD;
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)&#xD;
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)&#xD;
sequence 5: T2 - R - T1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sequence 6</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.&#xD;
R(Reference): BR4002-1 (oral intake) 5mg single-dose&#xD;
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)&#xD;
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)&#xD;
sequence 6: T2 - T1 - R</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BR4002</intervention_name>
    <description>Administration to the T1 group: 5 mg of BR4002 (patch) will be attached using an applicator for 24 hours&#xD;
Administration to the T2 group: 5 mg of BR4002 (patch) will be attached without using an applicator for 24 hours</description>
    <arm_group_label>sequence 1</arm_group_label>
    <arm_group_label>sequence 2</arm_group_label>
    <arm_group_label>sequence 3</arm_group_label>
    <arm_group_label>sequence 4</arm_group_label>
    <arm_group_label>sequence 5</arm_group_label>
    <arm_group_label>sequence 6</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BR4002-1</intervention_name>
    <description>Administration to the R group: 5 mg of BR4002-1 (oral formulation) will be administered with 150 mL of water</description>
    <arm_group_label>sequence 1</arm_group_label>
    <arm_group_label>sequence 2</arm_group_label>
    <arm_group_label>sequence 3</arm_group_label>
    <arm_group_label>sequence 4</arm_group_label>
    <arm_group_label>sequence 5</arm_group_label>
    <arm_group_label>sequence 6</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy adults aged ≥ 19 and ≤ 55 years at screening&#xD;
&#xD;
          2. Body weight of ≥ 50 kg with calculated body mass index (BMI) of ≥ 18.0 to ≤ 29.0 kg/m2&#xD;
&#xD;
          3. Determined eligible based on the results of physical examination and investigator&#xD;
             questioning conducted according to this protocol. That is, absence of congenital or&#xD;
             chronic disease, and absence of pathological symptoms or findings based on medical&#xD;
             examination in the last 3 years.&#xD;
&#xD;
          4. Determined eligible based on the results of the laboratory tests and electrocardiogram&#xD;
             (ECG) conducted according to this protocol&#xD;
&#xD;
          5. Voluntarily decided to participate in the study and provided written consent to follow&#xD;
             precautions after receiving a detailed explanation on this study and fully&#xD;
             understanding the information&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity to, or history of clinically significant hypersensitivity to&#xD;
             donepezil hydrochloride, piperidine derivatives or any ingredients of piperidine&#xD;
             derivatives, or other drugs (aspirin, antibiotics, etc.)&#xD;
&#xD;
          2. Hereditary disorders including galactose intolerance, Lapp lactase deficiency, and&#xD;
             glucose-galactose malabsorption&#xD;
&#xD;
          3. History of heart disease such as sinus node syndrome, intra-atrial conduction&#xD;
             disturbance or atrioventricular junctional conduction disturbance&#xD;
&#xD;
          4. Ongoing administration of non-steroidal anti-inflammatory drugs or history of peptic&#xD;
             ulcer&#xD;
&#xD;
          5. History of asthma or obstructive pulmonary disease&#xD;
&#xD;
          6. Extrapyramidal disorder&#xD;
&#xD;
          7. Psychotic disorders or drug addiction&#xD;
&#xD;
          8. Presence or prior history of a gastrointestinal disorder or prior history of&#xD;
             gastrointestinal surgery or skin graft that may affect the absorption of the IP&#xD;
&#xD;
          9. Presence or prior history of clinically significant cardiovascular, respiratory,&#xD;
             hepatic, renal, neurological, endocrine, hematological and oncological, psychotic, or&#xD;
             urinary disease&#xD;
&#xD;
         10. Clinically significant hypotension (systolic blood pressure &lt; 90 mmHg) or hypertension&#xD;
             (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 95 mmHg) at&#xD;
             screening&#xD;
&#xD;
         11. Any of the following results from screening tests:&#xD;
&#xD;
               -  AST or ALT &gt; 2 times the upper limit of normal&#xD;
&#xD;
               -  Total bilirubin &gt; 2.0 mg/dL&#xD;
&#xD;
               -  Estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73m2&#xD;
&#xD;
         12. QTc &gt; 450 ms or any clinically significant abnormal finding from an ECG result at&#xD;
             screening&#xD;
&#xD;
         13. Continuous alcohol intake or inability to stop drinking during the study period&#xD;
&#xD;
         14. Continuous smoking or inability to stop smoking throughout the hospitalization during&#xD;
             the study period&#xD;
&#xD;
         15. Participated in another clinical study or bioequivalence study within 6 months prior&#xD;
             to the first administration of the IP&#xD;
&#xD;
         16. Donated whole blood within 60 days or blood components within 30 days, or received&#xD;
             blood transfusion within 30 days prior to the first administration of the IP&#xD;
&#xD;
         17. Used any prescription drugs or herbal medicines within 14 days, or any&#xD;
             over-the-counter (OTC) drugs within 7 days prior to the first administration of the IP&#xD;
&#xD;
         18. Used drugs inducing and inhibiting drug-metabolizing enzymes, such as barbitals,&#xD;
             within 1 month prior to initiation of the study&#xD;
&#xD;
         19. Have been on a diet (especially grapefruit juice or its product) which may affect&#xD;
             absorption, distribution, metabolism, and excretion of the drug within 7 days prior to&#xD;
             the first administration of the IP&#xD;
&#xD;
         20. Do not agree to exclude the possibility of pregnancy by using medically acceptable&#xD;
             methods of contraception from the first day of administration of the IP up to 7 days&#xD;
             after the last day of administration of the IP&#xD;
&#xD;
         21. Unwillingness or inability to comply with the diet and lifestyle guidelines required&#xD;
             for the study&#xD;
&#xD;
         22. Clinically significant abnormal laboratory results or considered ineligible for study&#xD;
             participation by the investigator for any other reason&#xD;
&#xD;
         23. Women who are pregnant, have a positive serum/urine hCG test, or are breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sang-Heon Cho</last_name>
    <role>Principal Investigator</role>
    <affiliation>Inha University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Inha University Hospital</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>October 27, 2020</last_update_submitted>
  <last_update_submitted_qc>October 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2020</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>
  <!-- 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/NCT04462029
org study id: BR-DPZ-CT-102
nct id: NCT04462029
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is designed as a randomized, open-label, single-dose, 6x3 crossover study.
A total of 18 subjects will be randomized into 6 sequence groups. The investigational
      products will be administered according to the treatment groups (R, T1, and T2) assigned to
      each sequence group in Period 1, Period 2, and Period 3. In between each period, there will
      be a washout period (28 days) long enough for the administered IP to be metabolized and
      eliminated.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetic variables -Area Under the concentration-time Curve from time 0 to t after single dosing(AUCt) of BR4002 and BR4002-1
time frame: 0~240 hours after medication
description: PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.
measure: Pharmacokinetic variables - maximum observed plasma concentration(Cmax) of BR4002 and BR4002-1
time frame: 0~240 hours after medication
description: PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.
measure: Pharmacokinetic variables - Area Under the concentration-time Curve from time 0 to infinite after single dosing(AUCinf) of BR4002 and BR4002-1
time frame: 0~240 hours after medication
description: PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.
measure: Pharmacokinetic variables - Time of occurrence of Cmax(Tmax) of BR4002 and BR4002-1
time frame: 0~240 hours after medication
description: PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.
arm group label: sequence 1
arm group type: Other
description: A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.
R(Reference): BR4002-1 (oral intake) 5mg single-dose
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)
sequence 1: R - T1 - T2
arm group label: sequence 2
arm group type: Other
description: A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.
R(Reference): BR4002-1 (oral intake) 5mg single-dose
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)
sequence 2: R - T2 - T1
arm group label: sequence 3
arm group type: Other
description: A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.
R(Reference): BR4002-1 (oral intake) 5mg single-dose
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)
sequence 3: T1 - R - T2
arm group label: sequence 4
arm group type: Other
description: A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.
R(Reference): BR4002-1 (oral intake) 5mg single-dose
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)
sequence 4: T1 - T2 - R
arm group label: sequence 5
arm group type: Other
description: A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.
R(Reference): BR4002-1 (oral intake) 5mg single-dose
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)
sequence 5: T2 - R - T1
arm group label: sequence 6
arm group type: Other
description: A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated.
R(Reference): BR4002-1 (oral intake) 5mg single-dose
T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator)
T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator)
sequence 6: T2 - T1 - R
intervention type: Drug
intervention name: BR4002
description: Administration to the T1 group: 5 mg of BR4002 (patch) will be attached using an applicator for 24 hours
Administration to the T2 group: 5 mg of BR4002 (patch) will be attached without using an applicator for 24 hours
arm group label: sequence 1
arm group label: sequence 2
arm group label: sequence 3
arm group label: sequence 4
arm group label: sequence 5
arm group label: sequence 6
intervention type: Drug
intervention name: BR4002-1
description: Administration to the R group: 5 mg of BR4002-1 (oral formulation) will be administered with 150 mL of water
arm group label: sequence 1
arm group label: sequence 2
arm group label: sequence 3
arm group label: sequence 4
arm group label: sequence 5
arm group label: sequence 6
criteria: 
gender: All
minimum age: 19 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sang-Heon Cho
role: Principal Investigator
affiliation: Inha University Hospital
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Alzheimer Disease