<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/NCT03785652</url>
  </required_header>
  <id_info>
    <org_study_id>LY03005-CHN-204</org_study_id>
    <nct_id>NCT03785652</nct_id>
  </id_info>
  <brief_title>Dose-Finding Clinical Trial to Evaluate the Efficacy and Safety of LY03005 Extended-release Tablets in the Treatment of Major Depressive Disorder (MDD)</brief_title>
  <official_title>Multicenter,Randomized,Double-blind,Placebo,Parallel-controlled,Dose-Finding Clinical Trial to Evaluate the Efficacy and Safety of LY03005 Extended-release Tablets in the Treatment of Major Depressive Disorder (MDD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Luye Pharma Group Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shandong Luye Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Luye Pharma Group 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 was a multicenter, randomized, double-blind, placebo, parallel-controlled,&#xD;
      dose-finding Phase II clinical trial to find the optimal dose of LY03005 Extended-release&#xD;
      Tablets for the treatment of MDD and to evaluate the preliminary efficacy and safety,&#xD;
      providing a basis for the design of phase III clinical trials and the determination of dosing&#xD;
      regimens.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study consisted of two periods: a screening and washout period of 2 weeks (recommended 8&#xD;
      days) and a double-blind treatment period (6 weeks). The first period is the screening and&#xD;
      washing period, the longest is 14 days and the shortest is 8 days (recommended 8 days), in&#xD;
      which the enrolled MDD subjects will start a one-week placebo wash period and receive&#xD;
      prescribed a placebo, 2 pills once a day for 7 consecutive days. The second period was a&#xD;
      double-blind treatment period of 6 weeks. After the placebo washout period, 260 enrolled&#xD;
      subjects were randomized into one of 5 study groups in the 1:1:1:1:1 ratio, 4 LY03005&#xD;
      Extended-release Tablets treatment groups with different dose or 1 placebo group. Subjects&#xD;
      were given investigatory drug or placebo according to the protocol, 4 pills once a day and&#xD;
      followed up at the end of 1, 2, 4 and 6 weeks.&#xD;
&#xD;
      Effectiveness of the investigational drug was evaluated using 17 Hamilton Depression Scale&#xD;
      (HAM-D17), Montgomery-Asberg Depression Scale (MADRS), Hamilton Anxiety Scale (HAMA),&#xD;
      Clinical Global Impression Scale (CGI) and Visual Analog Scale-Pain intensity (VAS-PI)&#xD;
      scores. Safety of the treatment was evaluated by adverse events, vital signs, laboratory&#xD;
      measurements (blood routine, urine routine, blood biochemistry and serology), 12-lead ECG,&#xD;
      physical examination, the Arizona Sexual Experience Scale (ASEX) and the Columbia-Suicide&#xD;
      Severity Rating Scale (C-SSRS) scores.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 9, 2015</start_date>
  <completion_date type="Actual">October 31, 2015</completion_date>
  <primary_completion_date type="Actual">October 31, 2015</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hamilton Depression Scale</measure>
    <time_frame>8 weeks</time_frame>
    <description>Changes from baseline in the total score of 17 items of Hamilton Depression Scale (HAM-D17) at the end of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Montgomery- Åsberg Depression Rating Scale(MADRS)</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Changes from baseline in the 10-items Montgomery- Åsberg Depression Rating Scale(MADRS) total scores at the end of treatment;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression Scale - improvement (CGI-I)</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Changes in the Clinical Global Impression Scale - improvement (CGI-I) scores at the end of treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">260</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>LY03005 extended-release tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LY03005 extended-release tablets at 4 doses 40 mg, 80mg, 120mg or 160mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY03005 extended-release tablets 40 mg</intervention_name>
    <description>LY03005 extended-release tablets 40 mg group :40mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfas</description>
    <arm_group_label>LY03005 extended-release tablets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY03005 extended-release tablets 80 mg group</intervention_name>
    <description>LY03005 extended-release tablets 80 mg group :&#xD;
80mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfast</description>
    <arm_group_label>LY03005 extended-release tablets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY03005 extended-release tablets 120 mg group</intervention_name>
    <description>LY03005 extended-release tablets 120 mg group :&#xD;
120mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfast</description>
    <arm_group_label>LY03005 extended-release tablets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY03005 extended-release tablets 160 mg group</intervention_name>
    <description>LY03005 extended-release tablets 160 mg group :&#xD;
160mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfast</description>
    <arm_group_label>LY03005 extended-release tablets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo group</intervention_name>
    <description>Placebo group :&#xD;
Placebo ，orally once a day, at a regular morning time on an empty stomach or after breakfast</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female aged 18 to 65 years subjects from outpatient or inpatient;&#xD;
&#xD;
          2. Subjects who meet the diagnostic criteria for MDD in DSM-IV-TR (Diagnostic and&#xD;
             Statistical Manual of Mental Disorders, 4th Edition) with either single or recurrent&#xD;
             episodes (296.2/296.3) without psychotic characteristics;&#xD;
&#xD;
          3. Total scores of 17-item Hamilton Depression Scale (HAM-D17) ≥ 20 points at screening&#xD;
             and baseline visits；&#xD;
&#xD;
          4. First item (depressive mood) score of HAM-D17 scale ≥ 2 points at screening and&#xD;
             baseline visits;&#xD;
&#xD;
          5. Clinical global impression scale-disease severity (CGI-S) score ≥ 4 points at&#xD;
             screening and baseline visits;&#xD;
&#xD;
          6. At screening and baseline, women of childbearing age (e.g., women who have not&#xD;
             undergone surgical sterilization or less than one year after menopause) have a urine&#xD;
             negative pregnancy test result. Male and female subjects of childbearing age agree to&#xD;
             take effective contraceptive measures during the entire study period and at least 28&#xD;
             days after the last dose of investigatory drug;&#xD;
&#xD;
          7. Subjects voluntarily participate in the trial by signing the informed consent form and&#xD;
             are able to follow the schedule in the protocol for visits, treatment, laboratory&#xD;
             tests and other research procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergic or known to be allergic to venlafaxine and desvenlafaxine;&#xD;
&#xD;
          2. MDD subjects who were not responsive to the previous venlafaxine treatment with&#xD;
             sufficient amount and duration or TRD, to at least two different mechanisms of action&#xD;
             antidepressants with adequate amount and duration in the past;&#xD;
&#xD;
          3. Total scores of HAM-D17 scale at baseline was decreased ≥25% compared with the one at&#xD;
             screening;&#xD;
&#xD;
          4. There is a clear suicide attempt or behavior and score of the 3rd item (suicidal&#xD;
             thought) in HAM-D17 total scale ≥ 3 points;&#xD;
&#xD;
          5. Gestational and lactating women or the subjects of childbearing age who do not take&#xD;
             effective contraception or who do not agree to continue using contraception within 28&#xD;
             days of the last dose;&#xD;
&#xD;
          6. Suppressed subjects who also meet other diagnoses on the DSM-IV-TR axis I or received&#xD;
             the treatment for such diagnoses (including current or previous diagnosis of anorexia&#xD;
             nervosa or bulimia nervosa), or was diagnosed as dysthymia in the past 2 years;&#xD;
&#xD;
          7. MDD secondary to other mental illnesses or physical illnesses;&#xD;
&#xD;
          8. Those with a history of seizures (except for convulsions caused by febrile seizures in&#xD;
             children);&#xD;
&#xD;
          9. Those receiving electroconvulsive therapy (ECT) within 3 months prior to screening or&#xD;
             according to the investigator's judgment that ECT is currently required; Those who&#xD;
             have received systematic psychotherapy (interpersonal relationship therapy, dynamic&#xD;
             therapy, cognitive behavioral therapy) within 3 months prior to screening；Those who&#xD;
             have received transcranial magnetic stimulation (TMS) within 3 months prior to&#xD;
             screening, or have received light therapy within 2 weeks prior to screening;&#xD;
&#xD;
         10. Subjects who have regularly taken anti-depressants within 2 weeks prior to screening,&#xD;
             and have stopped the anti-depressants less than 2 weeks or psychotropic drugs for less&#xD;
             than 7 half-lives prior to study randomization (monoamine oxidase inhibitor for at&#xD;
             least 2 weeks, fluoxetine for at least 1 month);&#xD;
&#xD;
         11. Subjects who have seriously unstable cardiovascular, liver, kidneys, blood, endocrine&#xD;
             and other physical diseases or a medical history;&#xD;
&#xD;
         12. Hypertensive patients with poor blood pressure control (SBP≥140 mmHg or DBP≥90 mmHg at&#xD;
             screening and baseline);&#xD;
&#xD;
         13. There is a history of gastrointestinal disease known to interfere with drug absorption&#xD;
             or excretion or a history of surgery known to interfere with drug absorption or&#xD;
             excretion;&#xD;
&#xD;
         14. A history of increased intra-ocular pressure or narrow-angle glaucoma;&#xD;
&#xD;
         15. Clinically significant abnormalities based in investigators judgment during screening&#xD;
             (for example, such as alanine aminotransferase (ALT) or aspartate aminotransferase&#xD;
             (AST) is 1.5 times higher than upper limit of normal range; creatinine (Cr) is higher&#xD;
             than the upper limit of normal ranges and clinical significant abnormal thyroid&#xD;
             function);&#xD;
&#xD;
         16. Electrocardiogram (ECG) abnormalities are clinically significant at screening and the&#xD;
             investigators believe that it is inappropriate for the subjects to be enrolled, such&#xD;
             as QTc interval ≥450 ms for male and QTc interval ≥460 ms for female;&#xD;
&#xD;
         17. Those who have participated in other clinical trials within 3 months prior to&#xD;
             screening;&#xD;
&#xD;
         18. Those with serious acute or chronic diseases, mental illnesses or clinically&#xD;
             significant abnormalities in laboratory tests, of which investigators believe that the&#xD;
             subjects are not suitable for this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Approval Letter of Ethics Committee of The Sixth Hospital of Peking University</name>
      <address>
        <city>Haidian District,</city>
        <state>Beijing</state>
        <zip>100191</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>December 21, 2018</last_update_submitted>
  <last_update_submitted_qc>December 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 24, 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>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03785652
org study id: LY03005-CHN-204
nct id: NCT03785652
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study was a multicenter, randomized, double-blind, placebo, parallel-controlled,
      dose-finding Phase II clinical trial to find the optimal dose of LY03005 Extended-release
      Tablets for the treatment of MDD and to evaluate the preliminary efficacy and safety,
      providing a basis for the design of phase III clinical trials and the determination of dosing
      regimens.
The study consisted of two periods: a screening and washout period of 2 weeks (recommended 8
      days) and a double-blind treatment period (6 weeks). The first period is the screening and
      washing period, the longest is 14 days and the shortest is 8 days (recommended 8 days), in
      which the enrolled MDD subjects will start a one-week placebo wash period and receive
      prescribed a placebo, 2 pills once a day for 7 consecutive days. The second period was a
      double-blind treatment period of 6 weeks. After the placebo washout period, 260 enrolled
      subjects were randomized into one of 5 study groups in the 1:1:1:1:1 ratio, 4 LY03005
      Extended-release Tablets treatment groups with different dose or 1 placebo group. Subjects
      were given investigatory drug or placebo according to the protocol, 4 pills once a day and
      followed up at the end of 1, 2, 4 and 6 weeks.

      Effectiveness of the investigational drug was evaluated using 17 Hamilton Depression Scale
      (HAM-D17), Montgomery-Asberg Depression Scale (MADRS), Hamilton Anxiety Scale (HAMA),
      Clinical Global Impression Scale (CGI) and Visual Analog Scale-Pain intensity (VAS-PI)
      scores. Safety of the treatment was evaluated by adverse events, vital signs, laboratory
      measurements (blood routine, urine routine, blood biochemistry and serology), 12-lead ECG,
      physical examination, the Arizona Sexual Experience Scale (ASEX) and the Columbia-Suicide
      Severity Rating Scale (C-SSRS) scores.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Hamilton Depression Scale
time frame: 8 weeks
description: Changes from baseline in the total score of 17 items of Hamilton Depression Scale (HAM-D17) at the end of treatment
measure: Montgomery- Åsberg Depression Rating Scale(MADRS)
time frame: 8 Weeks
description: Changes from baseline in the 10-items Montgomery- Åsberg Depression Rating Scale(MADRS) total scores at the end of treatment;
measure: Clinical Global Impression Scale - improvement (CGI-I)
time frame: 8 Weeks
description: Changes in the Clinical Global Impression Scale - improvement (CGI-I) scores at the end of treatment
arm group label: LY03005 extended-release tablets
arm group type: Experimental
description: LY03005 extended-release tablets at 4 doses 40 mg, 80mg, 120mg or 160mg
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo tablet
intervention type: Drug
intervention name: LY03005 extended-release tablets 40 mg
description: LY03005 extended-release tablets 40 mg group :40mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfas
arm group label: LY03005 extended-release tablets
intervention type: Drug
intervention name: LY03005 extended-release tablets 80 mg group
description: LY03005 extended-release tablets 80 mg group :
80mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfast
arm group label: LY03005 extended-release tablets
intervention type: Drug
intervention name: LY03005 extended-release tablets 120 mg group
description: LY03005 extended-release tablets 120 mg group :
120mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfast
arm group label: LY03005 extended-release tablets
intervention type: Drug
intervention name: LY03005 extended-release tablets 160 mg group
description: LY03005 extended-release tablets 160 mg group :
160mg/day，orally once a day, at a regular morning time on an empty stomach or after breakfast
arm group label: LY03005 extended-release tablets
intervention type: Drug
intervention name: Placebo group
description: Placebo group :
Placebo ，orally once a day, at a regular morning time on an empty stomach or after breakfast
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
sharing ipd: No