Octohydroaminoacridine Succinate Tablet for Mild-to-Moderate Alzheimer's Disease
Primary Purpose
Alzheimer Disease
Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Octohydroaminoacridine Succinate
Aricept
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease
Eligibility Criteria
Inclusion Criteria:
- Age 50-85 years (including 50 and 85 years old), male or female;
- Diagnose probable AD in accordance with the National Institute Aging and Alzheimer's Association (NIA-AA) (2011);
- Mild-to-moderate AD patients, MMSE 11-26 (including 11 and 26, primary school education subjects from 11 to 22);
- Hachinski Incheinic Score (HIS) less than 4 points;
- Hamilton depression scale /17 Version (HAMD) score less than 10 points;
- Memory decline at least 12 months, and the decline is progressive;
- Brain MRI examination was done within 6 months before screening;
- Neurological examination had no obvious signs (except due to AD disease or peripheral injury);
- Females were postmenopausal (menopause beyond 24 weeks), or accepted the surgical sterilization, or women of childbearing age agreed to take effective contraceptive measures during the study. Women of childbearing age or menopausal time shorter than 24 weeks must do the urine pregnancy test and results to be negative during the screening period;
- Subjects should have stable and reliable caregivers, or have frequent contact with caregivers (at least 4 days per week, at least 2 hours per day), caregivers will help patients to participate in the study. Caregivers must accompany the subjects in the study visit to provide valuable information for the NPI, ADCS-ADL and CIBIC-plus scales assessments;
- Subjects have at least primary school education level, and have the ability to complete the determination of cognitive ability assessments and other tests;
- The participants and legal guardian must sign informed consent.
Exclusion Criteria:
- Brain MRI examination showed significant focal lesions, moderate-to-severe white matter lesions, and key parts lacunar infarction such as the thalamus, hippocampus, entorhinal cortex, cortical and subcortical gray matter nuclei;
- Other type of dementia except AD;
- Suffered from nervous system diseases (including stroke, optic myelopathy, Parkinson's disease, epilepsy, etc);
- Psychotic patients, according to the DSM-5 criteria, include schizophrenia or other psychiatry disorders, bipolar disorder, major depression disorder, or delirium;
- Abnormal laboratory test results: HBsAg and HBeAg and/or HbcAb positive and active stage of hepatitis B, liver function (ALT, AST) more than 1.2 times of the upper limit of the normal range, Cr exceeds the upper limit of normal, white blood cell count less than 4 x 109/L or platelet less than 100 x 109/L, hemoglobin less than 100g/L, blood glucose concentration of diabetic subjects (random) is more than 13.9mmol/L;
- Systolic pressure was more than 160mmHg or less than 90mmHg, diastolic blood pressure was more than 100mmHg or less than 60mmHg;
- With unstable or serious heart, lung, liver, kidney and hematopoietic system diseases (including unstable angina, myocardial infarction, uncontrolled asthma, gastric cancer, et al), or resting heart rate after 10 minutes of rest was less than 60 BPM, or QTc (QTc B (Bazett's correction value) or QTc F (Fridericia's correction value)) was equal or greater than 450msec, or with bundle branch block, the QTc B or QTc F was equal or greater than 480msec, or the researchers estimate there were abnormal EKG results which cannot be randomized to the study;
- There was uncorrected of visual and auditory disturbances, and neuropsychological tests and scale assessments cannot be completed by the subject;
- Subject was currently using Alzheimer's disease drugs and cannot be terminate the treatment;
- Subjects that cannot take the test drug according to the prescription should be excluded;
- Alcohol abuse or drug abuse;
- Pregnant or lactating women;
- Participated in other clinical pharmacological tests within 30 days before screening visit;
- The researchers believe that the subject was impossible to complete the study;
- Participants were employees of the study and immediate family members, employees of CRO company or sponsor and their immediate family members.
Sites / Locations
- Shanghai Mental Health CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
Octohydroaminoacridine Succinate Tablet
Aricept
Placebo
Arm Description
Octohydroaminoacridine Succinate Tablet 4mg P.O. tid
Aricept 5mg/day P.O.
Placebo P.O. tid
Outcomes
Primary Outcome Measures
Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog)
The change of ADAS-Cog from baseline to endpoint among three arms.
Secondary Outcome Measures
Clinician's Interview Based Impression of Change - plus (CIBIC+)
The change of CIBIC+ from baseline to endpoint among three arms.
Activities of Daily Living (ADL)
The change of ADL from baseline to endpoint among three arms.
Neuropsychiatric Inventory (NPI)
The change of NPI from baseline to endpoint among three arms.
Full Information
NCT ID
NCT03283059
First Posted
September 12, 2017
Last Updated
October 20, 2019
Sponsor
Shanghai Mental Health Center
Collaborators
Changchun Huayang High-tech Co., Ltd, Jiangsu Sheneryang High-tech Co., Ltd
1. Study Identification
Unique Protocol Identification Number
NCT03283059
Brief Title
Octohydroaminoacridine Succinate Tablet for Mild-to-Moderate Alzheimer's Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Unknown status
Study Start Date
August 16, 2017 (Actual)
Primary Completion Date
September 16, 2020 (Anticipated)
Study Completion Date
February 16, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Mental Health Center
Collaborators
Changchun Huayang High-tech Co., Ltd, Jiangsu Sheneryang High-tech Co., Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
600 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Octohydroaminoacridine Succinate Tablet
Arm Type
Experimental
Arm Description
Octohydroaminoacridine Succinate Tablet 4mg P.O. tid
Arm Title
Aricept
Arm Type
Active Comparator
Arm Description
Aricept 5mg/day P.O.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo P.O. tid
Intervention Type
Drug
Intervention Name(s)
Octohydroaminoacridine Succinate
Intervention Description
Octohydroaminoacridine Succinate Tablet:4mg P.O. tid
Intervention Type
Drug
Intervention Name(s)
Aricept
Intervention Description
Aricept 5mg/day, P.O.
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Placebo Tablet: P.O. tid
Primary Outcome Measure Information:
Title
Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog)
Description
The change of ADAS-Cog from baseline to endpoint among three arms.
Time Frame
26 weeks double-blind study and 28 weeks extention study
Secondary Outcome Measure Information:
Title
Clinician's Interview Based Impression of Change - plus (CIBIC+)
Description
The change of CIBIC+ from baseline to endpoint among three arms.
Time Frame
26 weeks double-blind study and 28 weeks extention study
Title
Activities of Daily Living (ADL)
Description
The change of ADL from baseline to endpoint among three arms.
Time Frame
26 weeks double-blind study and 28 weeks extention study
Title
Neuropsychiatric Inventory (NPI)
Description
The change of NPI from baseline to endpoint among three arms.
Time Frame
26 weeks double-blind study and 28 weeks extention study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 50-85 years (including 50 and 85 years old), male or female;
Diagnose probable AD in accordance with the National Institute Aging and Alzheimer's Association (NIA-AA) (2011);
Mild-to-moderate AD patients, MMSE 11-26 (including 11 and 26, primary school education subjects from 11 to 22);
Hachinski Incheinic Score (HIS) less than 4 points;
Hamilton depression scale /17 Version (HAMD) score less than 10 points;
Memory decline at least 12 months, and the decline is progressive;
Brain MRI examination was done within 6 months before screening;
Neurological examination had no obvious signs (except due to AD disease or peripheral injury);
Females were postmenopausal (menopause beyond 24 weeks), or accepted the surgical sterilization, or women of childbearing age agreed to take effective contraceptive measures during the study. Women of childbearing age or menopausal time shorter than 24 weeks must do the urine pregnancy test and results to be negative during the screening period;
Subjects should have stable and reliable caregivers, or have frequent contact with caregivers (at least 4 days per week, at least 2 hours per day), caregivers will help patients to participate in the study. Caregivers must accompany the subjects in the study visit to provide valuable information for the NPI, ADCS-ADL and CIBIC-plus scales assessments;
Subjects have at least primary school education level, and have the ability to complete the determination of cognitive ability assessments and other tests;
The participants and legal guardian must sign informed consent.
Exclusion Criteria:
Brain MRI examination showed significant focal lesions, moderate-to-severe white matter lesions, and key parts lacunar infarction such as the thalamus, hippocampus, entorhinal cortex, cortical and subcortical gray matter nuclei;
Other type of dementia except AD;
Suffered from nervous system diseases (including stroke, optic myelopathy, Parkinson's disease, epilepsy, etc);
Psychotic patients, according to the DSM-5 criteria, include schizophrenia or other psychiatry disorders, bipolar disorder, major depression disorder, or delirium;
Abnormal laboratory test results: HBsAg and HBeAg and/or HbcAb positive and active stage of hepatitis B, liver function (ALT, AST) more than 1.2 times of the upper limit of the normal range, Cr exceeds the upper limit of normal, white blood cell count less than 4 x 109/L or platelet less than 100 x 109/L, hemoglobin less than 100g/L, blood glucose concentration of diabetic subjects (random) is more than 13.9mmol/L;
Systolic pressure was more than 160mmHg or less than 90mmHg, diastolic blood pressure was more than 100mmHg or less than 60mmHg;
With unstable or serious heart, lung, liver, kidney and hematopoietic system diseases (including unstable angina, myocardial infarction, uncontrolled asthma, gastric cancer, et al), or resting heart rate after 10 minutes of rest was less than 60 BPM, or QTc (QTc B (Bazett's correction value) or QTc F (Fridericia's correction value)) was equal or greater than 450msec, or with bundle branch block, the QTc B or QTc F was equal or greater than 480msec, or the researchers estimate there were abnormal EKG results which cannot be randomized to the study;
There was uncorrected of visual and auditory disturbances, and neuropsychological tests and scale assessments cannot be completed by the subject;
Subject was currently using Alzheimer's disease drugs and cannot be terminate the treatment;
Subjects that cannot take the test drug according to the prescription should be excluded;
Alcohol abuse or drug abuse;
Pregnant or lactating women;
Participated in other clinical pharmacological tests within 30 days before screening visit;
The researchers believe that the subject was impossible to complete the study;
Participants were employees of the study and immediate family members, employees of CRO company or sponsor and their immediate family members.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shifu Xiao, M.D., Ph.D.
Phone
+86 21 64387250
Ext
73441
Email
xiaoshifu@msn.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tao Wang, M.D., Ph.D.
Phone
+86 18017311279
Email
wtshhwy@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shifu Xiao, M.D., Ph.D.
Organizational Affiliation
Shanghai Mental Health Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Mental Health Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shifu Xiao, M.D., Ph.D.
Phone
+86 21 64387250
Ext
73441
Email
xiaoshifu@msn.com
First Name & Middle Initial & Last Name & Degree
Tao Wang, M.D., Ph.D.
Phone
+86 18017311279
Email
wtshhwy@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Other researchers should apply to the sponsor.
Learn more about this trial
Octohydroaminoacridine Succinate Tablet for Mild-to-Moderate Alzheimer's Disease
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