<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/NCT03790982</url>
  </required_header>
  <id_info>
    <org_study_id>AD-35-II-01</org_study_id>
    <nct_id>NCT03790982</nct_id>
  </id_info>
  <brief_title>Evaluate the Safety and Efficacy of AD-35 Tablet in Subjects With Mild to Moderate Alzheimer's Disease</brief_title>
  <acronym>WAY</acronym>
  <official_title>A Randomized, Double Blind, Placebo Controlled, Parallel-Group 52-week Multicenter Phase II Study to Investigate the Safety, Efficacy and Pharmacokinetics of AD-35 Tablet in Subjects With Mild to Moderate Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhejiang Hisun Pharmaceutical Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhejiang Hisun 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>
      Brief summary: This is a phase II study to investigate the safety, preliminary efficacy and&#xD;
      pharmacokinetics of AD-35 tablet in patients with mild to moderate Alzheimer's Disease. This&#xD;
      study is to be run in China involving 21 sites. It will enroll approximately 480 patients to&#xD;
      ensure 240 randomized with mild to moderate Alzheimer's Disease. The treatment period is 52&#xD;
      weeks and total study duration per patient is approximately 57 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this multicenter, randomized, double blind, parallel-group, placebo controlled phase II&#xD;
      study, 240 patients with mild to moderate Alzheimer's Disease are planned to be enrolled and&#xD;
      randomly assigned 1:1:1 to receive placebo, or different doses of AD-35 tablet (30 or 60 mg).&#xD;
      After the first 26 weeks, subjects on active study drug will remain on the current doses, and&#xD;
      subjects assigned to placebo will be randomized to receive 30 mg and 60 mg AD-35 tablet in a&#xD;
      1:1 ratio, respectively, for the second 26 weeks. This study will evaluate the safety,&#xD;
      preliminary efficacy and pharmacokinetics of AD-35 tablets in patients with mild to moderate&#xD;
      Alzheimer's Disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">July 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2020</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Parallel Assignment, Multiple Groups, Multiple Centers</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double (Participant, Investigator)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11 scores</measure>
    <time_frame>Week 26</time_frame>
    <description>Changes in the total of ADAS-Cog11 scores of treatment compared with baseline. The score ranged from 0 to 75, and the higher the score, the greater the cognitive impairment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Alzheimer's Disease Cooperative Study-clinical global impression of change (ADCS-CGIC ) scores</measure>
    <time_frame>Week 26</time_frame>
    <description>Changes in ADCS-CGIC scores of treatment compared with baseline. The overall condition of the disease change is assessed (improved or deteriorated) by the doctor and the patient, and the 8-point scoring method (0-7 points) was adopted.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in ADAS-Cog11 scores</measure>
    <time_frame>Week 6, week 13, week 39, week52</time_frame>
    <description>Changes in ADCS-CGIC scores of treatment compared with baseline</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in ADCS-CGIC scores</measure>
    <time_frame>Week 6, week 13, week 39, week52</time_frame>
    <description>Changes in ADCS-CGIC scores of treatment compared with baseline</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in Mini-mental state examination (MMSE) scores</measure>
    <time_frame>Week 6, week 13, week 26, week 39, week52</time_frame>
    <description>Changes in MMSE scores of treatment compared with baseline. Each item has a correct score of 1 and an error score of 0.The total score ranges from 0 to 30, and the normal and abnormal boundary values are related to education degree. The lower the boundary value was the cognitive impairment, and the above was normal.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">240</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Placebo of AD-35 60mg /AD-35 30mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo of AD-35 60 mg Placebo of AD-35 30mg x two tablets, once daily in the first 26 weeks (oral), then AD-35 30mg +Placebo of AD-35 30mg, once daily in the second 26 weeks (oral)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo of AD-35 60mg /AD-35 60mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo of AD-35 60 mg Placebo of AD-35 30mg x two tablets, once daily in the first 26 weeks (oral), then AD-35 30mg x two tablets, once daily in the second 26 weeks (oral)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AD-35 30 mg+Placebo of AD-35 30 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AD-35 30 mg + Placebo of AD-35 30 mg AD-35 30 mg + Placebo of AD-35 30 mg, once daily for 52 weeks (oral)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AD-35 60 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AD-35 60 mg AD-35 30 mg× two tablets, once daily for 52 weeks (oral)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo of AD-35 60mg /AD-35 30mg</intervention_name>
    <description>Placebo 60mg, oral, 1st 26 weeks; AD-35 30mg +Placebo of AD-35 30mg oral 2nd 26 weeks.</description>
    <arm_group_label>Placebo of AD-35 60mg /AD-35 30mg</arm_group_label>
    <other_name>Placebo of AD-35</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo of AD-35 60mg /AD-35 60mg</intervention_name>
    <description>Placebo 60mg, oral, 1st 26 weeks; AD-35 60mg oral, 2nd 26 weeks.</description>
    <arm_group_label>Placebo of AD-35 60mg /AD-35 60mg</arm_group_label>
    <other_name>Placebo 60mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AD-35 30 mg + Placebo of AD-35 30 mg</intervention_name>
    <description>AD-35 30 mg + Placebo of AD-35 30 mg AD-35 30 mg + Placebo of AD-35 30 mg, Oral, 52 weeks.</description>
    <arm_group_label>AD-35 30 mg+Placebo of AD-35 30 mg</arm_group_label>
    <other_name>AD-35</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AD-35 60 mg</intervention_name>
    <description>AD-35 60 mg AD-35 30 mg x two tablets, oral, 52 weeks.</description>
    <arm_group_label>AD-35 60 mg</arm_group_label>
    <other_name>AD-35</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women, 50-75 years of age.&#xD;
&#xD;
          -  Formal education of five or more years.&#xD;
&#xD;
          -  Diagnosed of probable AD in accordance with the NINCDS/ADRDA criteria (2011).&#xD;
&#xD;
          -  Mild or moderate AD subjects: MMSE Score of 15-26 and CDR Score ≥ 0.5 (CDR memory&#xD;
             score ≥ 0.5).&#xD;
&#xD;
          -  Subjects must have a brain magnetic resonance imaging (MRI) scan that is consistent&#xD;
             with a clinical diagnosis of probable AD. Brain atrophy and medial temporal lobe&#xD;
             atrophy visual assessment scale MTA grading &gt;2 points. Mild white matter degeneration&#xD;
             may occur, but Fazekas less than or equal to 2 points and supratentorial lacunar&#xD;
             infarction lesions less than or equal to 3 points.&#xD;
&#xD;
          -  The total score of modified Hachinski ischemia scale (MHIS) ≤ 4.&#xD;
&#xD;
          -  Hamilton depression scale (HAMD) has a total score ≤ 17.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Visual, hearing and verbal communication of subjects cannot meet the needs of&#xD;
             cognitive function evaluation.&#xD;
&#xD;
          -  Inability to tolerate MRI procedures or contraindication to MRI, (such as implanted in&#xD;
             the body, MRI incompatible pacemakers, implantable cardioverter defibrillators,&#xD;
             cochlear implants, aneurysm clips, implanted injection pump, implanted nerve&#xD;
             stimulator, metallic splinters in the eye, other magnetic, electrical and other metal&#xD;
             implants) [note], or any other situation, in the judgment of the Investigator, is not&#xD;
             suitable for magnetic resonance imaging (MRI).&#xD;
&#xD;
          -  The investigators believe that other severe or unstable conditions may interfere with&#xD;
             the cognitive evaluation in clinical trials.&#xD;
&#xD;
          -  Dementia caused by other reasons: vascular dementia, central nervous system infection,&#xD;
             endocrine system diseases (such as thyroid disease, parathyroid gland disease) and&#xD;
             other reasons.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianping Jia, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Xuanwu hospital, capital medical university, Beijing, China</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Department of Neurosurgery</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100010</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>December 29, 2018</last_update_submitted>
  <last_update_submitted_qc>December 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AD-35 tablet</keyword>
  <keyword>Alzheimer's Disease</keyword>
  <keyword>Phase II study</keyword>
  <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/NCT03790982
org study id: AD-35-II-01
nct id: NCT03790982
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Brief summary: This is a phase II study to investigate the safety, preliminary efficacy and
      pharmacokinetics of AD-35 tablet in patients with mild to moderate Alzheimer's Disease. This
      study is to be run in China involving 21 sites. It will enroll approximately 480 patients to
      ensure 240 randomized with mild to moderate Alzheimer's Disease. The treatment period is 52
      weeks and total study duration per patient is approximately 57 weeks.
In this multicenter, randomized, double blind, parallel-group, placebo controlled phase II
      study, 240 patients with mild to moderate Alzheimer's Disease are planned to be enrolled and
      randomly assigned 1:1:1 to receive placebo, or different doses of AD-35 tablet (30 or 60 mg).
      After the first 26 weeks, subjects on active study drug will remain on the current doses, and
      subjects assigned to placebo will be randomized to receive 30 mg and 60 mg AD-35 tablet in a
      1:1 ratio, respectively, for the second 26 weeks. This study will evaluate the safety,
      preliminary efficacy and pharmacokinetics of AD-35 tablets in patients with mild to moderate
      Alzheimer's Disease.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel Assignment, Multiple Groups, Multiple Centers
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double (Participant, Investigator)
measure: Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11 scores
time frame: Week 26
description: Changes in the total of ADAS-Cog11 scores of treatment compared with baseline. The score ranged from 0 to 75, and the higher the score, the greater the cognitive impairment
measure: Changes in Alzheimer's Disease Cooperative Study-clinical global impression of change (ADCS-CGIC ) scores
time frame: Week 26
description: Changes in ADCS-CGIC scores of treatment compared with baseline. The overall condition of the disease change is assessed (improved or deteriorated) by the doctor and the patient, and the 8-point scoring method (0-7 points) was adopted.
measure: Changes in ADAS-Cog11 scores
time frame: Week 6, week 13, week 39, week52
description: Changes in ADCS-CGIC scores of treatment compared with baseline
measure: Changes in ADCS-CGIC scores
time frame: Week 6, week 13, week 39, week52
description: Changes in ADCS-CGIC scores of treatment compared with baseline
measure: Changes in Mini-mental state examination (MMSE) scores
time frame: Week 6, week 13, week 26, week 39, week52
description: Changes in MMSE scores of treatment compared with baseline. Each item has a correct score of 1 and an error score of 0.The total score ranges from 0 to 30, and the normal and abnormal boundary values are related to education degree. The lower the boundary value was the cognitive impairment, and the above was normal.
arm group label: Placebo of AD-35 60mg /AD-35 30mg
arm group type: Placebo Comparator
description: Placebo of AD-35 60 mg Placebo of AD-35 30mg x two tablets, once daily in the first 26 weeks (oral), then AD-35 30mg +Placebo of AD-35 30mg, once daily in the second 26 weeks (oral)
arm group label: Placebo of AD-35 60mg /AD-35 60mg
arm group type: Placebo Comparator
description: Placebo of AD-35 60 mg Placebo of AD-35 30mg x two tablets, once daily in the first 26 weeks (oral), then AD-35 30mg x two tablets, once daily in the second 26 weeks (oral)
arm group label: AD-35 30 mg+Placebo of AD-35 30 mg
arm group type: Experimental
description: AD-35 30 mg + Placebo of AD-35 30 mg AD-35 30 mg + Placebo of AD-35 30 mg, once daily for 52 weeks (oral)
arm group label: AD-35 60 mg
arm group type: Experimental
description: AD-35 60 mg AD-35 30 mg× two tablets, once daily for 52 weeks (oral)
intervention type: Drug
intervention name: Placebo of AD-35 60mg /AD-35 30mg
description: Placebo 60mg, oral, 1st 26 weeks; AD-35 30mg +Placebo of AD-35 30mg oral 2nd 26 weeks.
arm group label: Placebo of AD-35 60mg /AD-35 30mg
other name: Placebo of AD-35
intervention type: Drug
intervention name: Placebo of AD-35 60mg /AD-35 60mg
description: Placebo 60mg, oral, 1st 26 weeks; AD-35 60mg oral, 2nd 26 weeks.
arm group label: Placebo of AD-35 60mg /AD-35 60mg
other name: Placebo 60mg
intervention type: Drug
intervention name: AD-35 30 mg + Placebo of AD-35 30 mg
description: AD-35 30 mg + Placebo of AD-35 30 mg AD-35 30 mg + Placebo of AD-35 30 mg, Oral, 52 weeks.
arm group label: AD-35 30 mg+Placebo of AD-35 30 mg
other name: AD-35
intervention type: Drug
intervention name: AD-35 60 mg
description: AD-35 60 mg AD-35 30 mg x two tablets, oral, 52 weeks.
arm group label: AD-35 60 mg
other name: AD-35
criteria: 
gender: All
minimum age: 50 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jianping Jia, PhD
role: Principal Investigator
affiliation: Xuanwu hospital, capital medical university, Beijing, China
facility: 
country: China
responsible party type: Sponsor
mesh term: Alzheimer Disease