<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/NCT03761004</url>
  </required_header>
  <id_info>
    <org_study_id>WD-1603-1001</org_study_id>
    <nct_id>NCT03761004</nct_id>
  </id_info>
  <brief_title>WD-1603 PK Study in Healthy Volunteers</brief_title>
  <official_title>A Phase 1 Single-Dose, Open-label, Sequential, Three-Period Crossover Study to Evaluate the Pharmacokinetics of WD-1603 Tablets in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hong Kong WD Pharmaceutical Co., Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hong Kong WD Pharmaceutical Co., Limited</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to investigate if the extended release formulation of WD-1603 generates&#xD;
      anticipated plasma concentration profile. The study is an open-label, sequential, 3-way&#xD;
      crossover study to evaluate if WD-1603 generates anticipated plasma levodopa exposure&#xD;
      compared to Sinemet IR tablets in healthy subjects. The study comprises of a medical&#xD;
      Screening visit, three 2-night (3-day) Treatment periods, 2 outpatient visits, and a&#xD;
      Follow-up visit. Study drug administration in each Treatment period is separated by a washout&#xD;
      interval of 5 days. The Follow-up visit will occur approximately 7 days (±1) following the&#xD;
      last study drug administration. The duration of subject participation, including screening,&#xD;
      is approximately 6 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Actual">September 5, 2019</completion_date>
  <primary_completion_date type="Actual">September 5, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>pre-dose（baseline）and specified time points up to 24 hours post-dose(as specified in the Arm/Group description)</time_frame>
    <description>the maximum plasma concentrations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-t</measure>
    <time_frame>pre-dose（baseline）and specified time points up to 24 hours post-dose(as specified in the Arm/Group description)</time_frame>
    <description>the areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-inf</measure>
    <time_frame>pre-dose（baseline）and specified time points up to 24 hours post-dose(as specified in the Arm/Group description)</time_frame>
    <description>the areas under the plasma concentration versus time curve extrapolated from 0 to infinity</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>WD-1603 single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>WD-1603 single dose:&#xD;
A single WD-1603 tablet after breakfast. Plasma samples for PK analysis will be collected at pre-dose (baseline) and 10 min, 30 min, 45 min and 1, 1.5, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours post-dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>WD-1603 BID dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>WD-1603 BID dose:&#xD;
A single WD-1603 tablet after breakfast, and a second WD-1603 tablet approximately 3 hours after completing lunch.&#xD;
Plasma samples for PK analysis will be collected at pre-dose (baseline) and 10 min, 30 min, 45 min and 1, 1.5, 2, 3, 4, 4.5, 5, 6, 7, 7.25, 7.5, 7.75, 8, 8.5, 9, 10, 10.5 11, 12, 16 and 24 hours post-dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sinemet single dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sinemet single dose:&#xD;
A single oral dose of Sinemet after breakfast. Plasma samples for PK analysis will be collected at pre-dose (baseline) and 10 min, 30 min, 45 min and 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12, 16 and 24 hours post-dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>carbidopa-levodopa</intervention_name>
    <description>single dose of WD-1603, BID dose of WD-1603 and Sinemet IR</description>
    <arm_group_label>Sinemet single dose</arm_group_label>
    <arm_group_label>WD-1603 BID dose</arm_group_label>
    <arm_group_label>WD-1603 single dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy adult male or female subjects, 18 to 55 years of age, inclusive, at the time&#xD;
             of signing the informed consent form (ICF).&#xD;
&#xD;
          2. A minimum body weight of 50.0 kg (110.0 lbs) and body mass index (BMI) between 18.0&#xD;
             and 30.0 kg/m2, inclusive, at screening.&#xD;
&#xD;
          3. Non-smoker for at least 3 months and tests negative on urine cotinine test.&#xD;
&#xD;
          4. Medically healthy subjects with clinically insignificant screening and Day -1&#xD;
             admission results (medical history, 12-lead electrocardiogram (ECG), physical&#xD;
             examination, vital signs, and laboratory tests) as determined by the Investigator or&#xD;
             designee.&#xD;
&#xD;
          5. Female subjects of childbearing potential with male sexual partners must be using and&#xD;
             willing to continue using medically acceptable contraception (true abstinence,&#xD;
             hormonal contraceptives [combined oral pill, patch, or vaginal ring], intrauterine&#xD;
             device, or double-barrier methods [condom with spermicide, diaphragm or cervical cap&#xD;
             with spermicide]) from Screening (or at least 3 months prior to Screening for hormonal&#xD;
             contraceptives) until at least 28 days after the last study drug administration.&#xD;
&#xD;
          6. Female subjects of non-childbearing potential must be either post-menopausal&#xD;
             (post-menopausal is defined as being amenorrheic for at least 1 year without another&#xD;
             cause and a follicle-stimulating hormone [FSH] level ≥26 IU/L) or surgically sterile&#xD;
             (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).&#xD;
&#xD;
          7. Male subjects with female sexual partners of childbearing potential must be using and&#xD;
             willing to continue using medically acceptable contraception (true abstinence,&#xD;
             vasectomy, or male condom for subjects plus an additional method of contraception for&#xD;
             their female partners) from Screening until 28 days following the last administration&#xD;
             of study drug.&#xD;
&#xD;
          8. Subjects are able to understand English and to give their signed informed consent&#xD;
             before any study-related procedures are performed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of serious allergic reaction or hypersensitivity to levodopa or carbidopa.&#xD;
&#xD;
          2. Subjects with, or a history of, narrow-angle glaucoma, cancer, diabetes, or any&#xD;
             clinically significant cardiovascular, respiratory, metabolic, renal, hepatic,&#xD;
             gastrointestinal, hematologic, dermatological, neurological, psychiatric, or other&#xD;
             major disorder.&#xD;
&#xD;
          3. History of clinically significant drug and/or food allergies as determined by the&#xD;
             Investigator or designee, or previous status asthmaticus.&#xD;
&#xD;
          4. Subject is not willing to abstain from alcohol for 48 hours prior to admission in&#xD;
             Day-1 until the final blood draw is complete through the final day of blood draws.&#xD;
&#xD;
          5. Use of prescription or non-prescription drugs, including herbal and dietary&#xD;
             supplements, within 7 days prior to the first dose of study medication.&#xD;
&#xD;
          6. Treatment with an investigational drug within 30 days prior to the first dosing, or&#xD;
             more than 5 half-lives of the compound which the subject was treated with , whichever&#xD;
             is longer.&#xD;
&#xD;
          7. Donation or loss of more than 500 mL whole blood within 30 days preceding the first&#xD;
             dose. Subjects must not donate blood or plasma during the study and for at least 56&#xD;
             days after the Follow-up visit.&#xD;
&#xD;
          8. Difficulty with venous access or unsuitable or unwilling to undergo catheter&#xD;
             insertion.&#xD;
&#xD;
          9. Self-reported substance or alcohol dependence (excluding nicotine and caffeine) within&#xD;
             the past 2 years prior to dosing, and/or has ever participated or plans to participate&#xD;
             in a substance or alcohol rehabilitation program to treat their substance or alcohol&#xD;
             dependence.&#xD;
&#xD;
         10. Typical weekly alcohol consumption of 14 alcoholic drinks. One standard alcoholic&#xD;
             drink is equivalent to 43 mL (1.5 oz.) hard liquor or 142 mL (5 oz.) wine or 341 mL&#xD;
             (12 oz.) beer.&#xD;
&#xD;
         11. Positive results in any of the serology tests of human immunodeficiency virus (HIV)&#xD;
             and hepatitis B and C infections.&#xD;
&#xD;
         12. Female subjects who are currently pregnant (have a positive pregnancy test) or&#xD;
             lactating or who are planning to become pregnant within 30 days of the last study drug&#xD;
             administration.&#xD;
&#xD;
         13. Positive urine drug at Screening and Day -1 admission. Given the long half-life of&#xD;
             tetrahydrocannabinol (THC) and its metabolites, subjects with a positive result for&#xD;
             THC at Screening may be included at the discretion of the investigator.&#xD;
&#xD;
         14. Positive breath alcohol test. Subjects with a positive result at Screening may be&#xD;
             rescheduled at the investigator's discretion.&#xD;
&#xD;
         15. Any condition that, in the opinion of the Investigator or designee, would complicate&#xD;
             or compromise the study or the well-being of the subject.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>INC Research Toronto, Inc.</name>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>February 11, 2020</last_update_submitted>
  <last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levodopa</mesh_term>
    <mesh_term>Carbidopa</mesh_term>
    <mesh_term>Carbidopa, levodopa drug combination</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/NCT03761004
org study id: WD-1603-1001
nct id: NCT03761004
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a pilot study to investigate if the extended release formulation of WD-1603 generates
      anticipated plasma concentration profile. The study is an open-label, sequential, 3-way
      crossover study to evaluate if WD-1603 generates anticipated plasma levodopa exposure
      compared to Sinemet IR tablets in healthy subjects. The study comprises of a medical
      Screening visit, three 2-night (3-day) Treatment periods, 2 outpatient visits, and a
      Follow-up visit. Study drug administration in each Treatment period is separated by a washout
      interval of 5 days. The Follow-up visit will occur approximately 7 days (±1) following the
      last study drug administration. The duration of subject participation, including screening,
      is approximately 6 weeks.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cmax
time frame: pre-dose（baseline）and specified time points up to 24 hours post-dose(as specified in the Arm/Group description)
description: the maximum plasma concentrations
measure: AUC0-t
time frame: pre-dose（baseline）and specified time points up to 24 hours post-dose(as specified in the Arm/Group description)
description: the areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation
measure: AUC0-inf
time frame: pre-dose（baseline）and specified time points up to 24 hours post-dose(as specified in the Arm/Group description)
description: the areas under the plasma concentration versus time curve extrapolated from 0 to infinity
arm group label: WD-1603 single dose
arm group type: Experimental
description: WD-1603 single dose:
A single WD-1603 tablet after breakfast. Plasma samples for PK analysis will be collected at pre-dose (baseline) and 10 min, 30 min, 45 min and 1, 1.5, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours post-dose.
arm group label: WD-1603 BID dose
arm group type: Experimental
description: WD-1603 BID dose:
A single WD-1603 tablet after breakfast, and a second WD-1603 tablet approximately 3 hours after completing lunch.
Plasma samples for PK analysis will be collected at pre-dose (baseline) and 10 min, 30 min, 45 min and 1, 1.5, 2, 3, 4, 4.5, 5, 6, 7, 7.25, 7.5, 7.75, 8, 8.5, 9, 10, 10.5 11, 12, 16 and 24 hours post-dose.
arm group label: Sinemet single dose
arm group type: Active Comparator
description: Sinemet single dose:
A single oral dose of Sinemet after breakfast. Plasma samples for PK analysis will be collected at pre-dose (baseline) and 10 min, 30 min, 45 min and 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12, 16 and 24 hours post-dose.
intervention type: Drug
intervention name: carbidopa-levodopa
description: single dose of WD-1603, BID dose of WD-1603 and Sinemet IR
arm group label: Sinemet single dose
arm group label: WD-1603 BID dose
arm group label: WD-1603 single dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Levodopa
mesh term: Carbidopa
mesh term: Carbidopa, levodopa drug combination