<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/NCT03283059</url>
  </required_header>
  <id_info>
    <org_study_id>OHAAS-III</org_study_id>
    <nct_id>NCT03283059</nct_id>
  </id_info>
  <brief_title>Octohydroaminoacridine Succinate Tablet for Mild-to-Moderate Alzheimer's Disease</brief_title>
  <official_title>Phase III Trial of Octohydroaminoacridine Succinate Tablet for Mild-to-Moderate Alzheimer's Disease: a 26 Weeks, Randomized, Double-blind, Double-dummy, Placebo- and Positive- Parallel Controlled and Extended Single Arm to 54 Weeks Multicentre Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Changchun Huayang High-tech Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jiangsu Sheneryang High-tech Co., Ltd</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Mental Health Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Inhibition of acetylcholinesterase has been a effective treatment for Alzheimer's disease.&#xD;
      Octohydroaminoacridine, a new acetylcholinesterase inhibitor, is a potential treatment for&#xD;
      Alzheimer's disease. The investigators conducted a 26 weeks, randomized, double-blind,&#xD;
      double-dummy, placebo- and positive- parallel controlled and extended single arm to 54 weeks&#xD;
      multicentre phase III clinical trial to investigate the effects of octohydroaminoacridine in&#xD;
      patients with mild-to-moderate Alzheimer's disease. Patients were randomized to receive&#xD;
      placebo thrice daily, or octohydroaminoacridine 4 mg/TID or ARICEPT 5mg/QD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 16, 2017</start_date>
  <completion_date type="Anticipated">February 16, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 16, 2020</primary_completion_date>
  <phase>Phase 3</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog)</measure>
    <time_frame>26 weeks double-blind study and 28 weeks extention study</time_frame>
    <description>The change of ADAS-Cog from baseline to endpoint among three arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinician's Interview Based Impression of Change - plus (CIBIC+)</measure>
    <time_frame>26 weeks double-blind study and 28 weeks extention study</time_frame>
    <description>The change of CIBIC+ from baseline to endpoint among three arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activities of Daily Living (ADL)</measure>
    <time_frame>26 weeks double-blind study and 28 weeks extention study</time_frame>
    <description>The change of ADL from baseline to endpoint among three arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychiatric Inventory (NPI)</measure>
    <time_frame>26 weeks double-blind study and 28 weeks extention study</time_frame>
    <description>The change of NPI from baseline to endpoint among three arms.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Octohydroaminoacridine Succinate Tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Octohydroaminoacridine Succinate Tablet 4mg P.O. tid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aricept</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Aricept 5mg/day P.O.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo P.O. tid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Octohydroaminoacridine Succinate</intervention_name>
    <description>Octohydroaminoacridine Succinate Tablet:4mg P.O. tid</description>
    <arm_group_label>Octohydroaminoacridine Succinate Tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aricept</intervention_name>
    <description>Aricept 5mg/day, P.O.</description>
    <arm_group_label>Aricept</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebo Tablet: P.O. tid</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 50-85 years (including 50 and 85 years old), male or female;&#xD;
&#xD;
          2. Diagnose probable AD in accordance with the National Institute Aging and Alzheimer's&#xD;
             Association (NIA-AA) (2011);&#xD;
&#xD;
          3. Mild-to-moderate AD patients, MMSE 11-26 (including 11 and 26, primary school&#xD;
             education subjects from 11 to 22);&#xD;
&#xD;
          4. Hachinski Incheinic Score (HIS) less than 4 points;&#xD;
&#xD;
          5. Hamilton depression scale /17 Version (HAMD) score less than 10 points;&#xD;
&#xD;
          6. Memory decline at least 12 months, and the decline is progressive;&#xD;
&#xD;
          7. Brain MRI examination was done within 6 months before screening;&#xD;
&#xD;
          8. Neurological examination had no obvious signs (except due to AD disease or peripheral&#xD;
             injury);&#xD;
&#xD;
          9. Females were postmenopausal (menopause beyond 24 weeks), or accepted the surgical&#xD;
             sterilization, or women of childbearing age agreed to take effective contraceptive&#xD;
             measures during the study. Women of childbearing age or menopausal time shorter than&#xD;
             24 weeks must do the urine pregnancy test and results to be negative during the&#xD;
             screening period;&#xD;
&#xD;
         10. Subjects should have stable and reliable caregivers, or have frequent contact with&#xD;
             caregivers (at least 4 days per week, at least 2 hours per day), caregivers will help&#xD;
             patients to participate in the study. Caregivers must accompany the subjects in the&#xD;
             study visit to provide valuable information for the NPI, ADCS-ADL and CIBIC-plus&#xD;
             scales assessments;&#xD;
&#xD;
         11. Subjects have at least primary school education level, and have the ability to&#xD;
             complete the determination of cognitive ability assessments and other tests;&#xD;
&#xD;
         12. The participants and legal guardian must sign informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Brain MRI examination showed significant focal lesions, moderate-to-severe white&#xD;
             matter lesions, and key parts lacunar infarction such as the thalamus, hippocampus,&#xD;
             entorhinal cortex, cortical and subcortical gray matter nuclei;&#xD;
&#xD;
          2. Other type of dementia except AD;&#xD;
&#xD;
          3. Suffered from nervous system diseases (including stroke, optic myelopathy, Parkinson's&#xD;
             disease, epilepsy, etc);&#xD;
&#xD;
          4. Psychotic patients, according to the DSM-5 criteria, include schizophrenia or other&#xD;
             psychiatry disorders, bipolar disorder, major depression disorder, or delirium;&#xD;
&#xD;
          5. Abnormal laboratory test results: HBsAg and HBeAg and/or HbcAb positive and active&#xD;
             stage of hepatitis B, liver function (ALT, AST) more than 1.2 times of the upper limit&#xD;
             of the normal range, Cr exceeds the upper limit of normal, white blood cell count less&#xD;
             than 4 x 109/L or platelet less than 100 x 109/L, hemoglobin less than 100g/L, blood&#xD;
             glucose concentration of diabetic subjects (random) is more than 13.9mmol/L;&#xD;
&#xD;
          6. Systolic pressure was more than 160mmHg or less than 90mmHg, diastolic blood pressure&#xD;
             was more than 100mmHg or less than 60mmHg;&#xD;
&#xD;
          7. With unstable or serious heart, lung, liver, kidney and hematopoietic system diseases&#xD;
             (including unstable angina, myocardial infarction, uncontrolled asthma, gastric&#xD;
             cancer, et al), or resting heart rate after 10 minutes of rest was less than 60 BPM,&#xD;
             or QTc (QTc B (Bazett's correction value) or QTc F (Fridericia's correction value))&#xD;
             was equal or greater than 450msec, or with bundle branch block, the QTc B or QTc F was&#xD;
             equal or greater than 480msec, or the researchers estimate there were abnormal EKG&#xD;
             results which cannot be randomized to the study;&#xD;
&#xD;
          8. There was uncorrected of visual and auditory disturbances, and neuropsychological&#xD;
             tests and scale assessments cannot be completed by the subject;&#xD;
&#xD;
          9. Subject was currently using Alzheimer's disease drugs and cannot be terminate the&#xD;
             treatment;&#xD;
&#xD;
         10. Subjects that cannot take the test drug according to the prescription should be&#xD;
             excluded;&#xD;
&#xD;
         11. Alcohol abuse or drug abuse;&#xD;
&#xD;
         12. Pregnant or lactating women;&#xD;
&#xD;
         13. Participated in other clinical pharmacological tests within 30 days before screening&#xD;
             visit;&#xD;
&#xD;
         14. The researchers believe that the subject was impossible to complete the study;&#xD;
&#xD;
         15. Participants were employees of the study and immediate family members, employees of&#xD;
             CRO company or sponsor and their immediate family members.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shifu Xiao, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Mental Health Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shifu Xiao, M.D., Ph.D.</last_name>
    <phone>+86 21 64387250</phone>
    <phone_ext>73441</phone_ext>
    <email>xiaoshifu@msn.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tao Wang, M.D., Ph.D.</last_name>
    <phone>+86 18017311279</phone>
    <email>wtshhwy@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai Mental Health Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200030</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shifu Xiao, M.D., Ph.D.</last_name>
      <phone>+86 21 64387250</phone>
      <phone_ext>73441</phone_ext>
      <email>xiaoshifu@msn.com</email>
    </contact>
    <contact_backup>
      <last_name>Tao Wang, M.D., Ph.D.</last_name>
      <phone>+86 18017311279</phone>
      <email>wtshhwy@163.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>October 20, 2019</last_update_submitted>
  <last_update_submitted_qc>October 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2019</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>Other researchers should apply to the sponsor.</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/NCT03283059
org study id: OHAAS-III
nct id: NCT03283059
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Inhibition of acetylcholinesterase has been a effective treatment for Alzheimer's disease.
      Octohydroaminoacridine, a new acetylcholinesterase inhibitor, is a potential treatment for
      Alzheimer's disease. The investigators conducted a 26 weeks, randomized, double-blind,
      double-dummy, placebo- and positive- parallel controlled and extended single arm to 54 weeks
      multicentre phase III clinical trial to investigate the effects of octohydroaminoacridine in
      patients with mild-to-moderate Alzheimer's disease. Patients were randomized to receive
      placebo thrice daily, or octohydroaminoacridine 4 mg/TID or ARICEPT 5mg/QD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog)
time frame: 26 weeks double-blind study and 28 weeks extention study
description: The change of ADAS-Cog from baseline to endpoint among three arms.
measure: Clinician's Interview Based Impression of Change - plus (CIBIC+)
time frame: 26 weeks double-blind study and 28 weeks extention study
description: The change of CIBIC+ from baseline to endpoint among three arms.
measure: Activities of Daily Living (ADL)
time frame: 26 weeks double-blind study and 28 weeks extention study
description: The change of ADL from baseline to endpoint among three arms.
measure: Neuropsychiatric Inventory (NPI)
time frame: 26 weeks double-blind study and 28 weeks extention study
description: The change of NPI from baseline to endpoint among three arms.
arm group label: Octohydroaminoacridine Succinate Tablet
arm group type: Experimental
description: Octohydroaminoacridine Succinate Tablet 4mg P.O. tid
arm group label: Aricept
arm group type: Active Comparator
description: Aricept 5mg/day P.O.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo P.O. tid
intervention type: Drug
intervention name: Octohydroaminoacridine Succinate
description: Octohydroaminoacridine Succinate Tablet:4mg P.O. tid
arm group label: Octohydroaminoacridine Succinate Tablet
intervention type: Drug
intervention name: Aricept
description: Aricept 5mg/day, P.O.
arm group label: Aricept
intervention type: Drug
intervention name: Placebos
description: Placebo Tablet: P.O. tid
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: No
last name: Shifu Xiao, M.D., Ph.D.
role: Principal Investigator
affiliation: Shanghai Mental Health Center
last name: Shifu Xiao, M.D., Ph.D.
phone: +86 21 64387250
phone ext: 73441
email: xiaoshifu@msn.com
last name: Tao Wang, M.D., Ph.D.
phone: +86 18017311279
email: wtshhwy@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Donepezil
sharing ipd: No
ipd description: Other researchers should apply to the sponsor.