Octohydroaminoacridine Succinate Tablet for Mild-to-Moderate Alzheimer's Disease

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

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.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Octohydroaminoacridine Succinate; Drug: Aricept; Drug: Placebos

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shifu Xiao, M.D., Ph.D.; Phone Number: 73441 +86 21 64387250; Email: xiaoshifu@msn.com
• Study Contact Backup: Name: Tao Wang, M.D., Ph.D.; Phone Number: +86 18017311279; Email: wtshhwy@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
      • Contact: Shifu Xiao, M.D., Ph.D.; Phone Number: 73441 +86 21 64387250; Email: xiaoshifu@msn.com
      • Contact: Tao Wang, M.D., Ph.D.; Phone Number: +86 18017311279; Email: wtshhwy@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 50-85 years (including 50 and 85 years old), male or female;
2. Diagnose probable AD in accordance with the National Institute Aging and Alzheimer's Association (NIA-AA) (2011);
3. Mild-to-moderate AD patients, MMSE 11-26 (including 11 and 26, primary school education subjects from 11 to 22);
4. Hachinski Incheinic Score (HIS) less than 4 points;
5. Hamilton depression scale /17 Version (HAMD) score less than 10 points;
6. Memory decline at least 12 months, and the decline is progressive;
7. Brain MRI examination was done within 6 months before screening;
8. Neurological examination had no obvious signs (except due to AD disease or peripheral injury);
9. 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;
10. 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;
11. Subjects have at least primary school education level, and have the ability to complete the determination of cognitive ability assessments and other tests;
12. The participants and legal guardian must sign informed consent.

Exclusion Criteria:

1. 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;
2. Other type of dementia except AD;
3. Suffered from nervous system diseases (including stroke, optic myelopathy, Parkinson's disease, epilepsy, etc);
4. Psychotic patients, according to the DSM-5 criteria, include schizophrenia or other psychiatry disorders, bipolar disorder, major depression disorder, or delirium;
5. 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;
6. Systolic pressure was more than 160mmHg or less than 90mmHg, diastolic blood pressure was more than 100mmHg or less than 60mmHg;
7. 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;
8. There was uncorrected of visual and auditory disturbances, and neuropsychological tests and scale assessments cannot be completed by the subject;
9. Subject was currently using Alzheimer's disease drugs and cannot be terminate the treatment;
10. Subjects that cannot take the test drug according to the prescription should be excluded;
11. Alcohol abuse or drug abuse;
12. Pregnant or lactating women;
13. Participated in other clinical pharmacological tests within 30 days before screening visit;
14. The researchers believe that the subject was impossible to complete the study;
15. Participants were employees of the study and immediate family members, employees of CRO company or sponsor and their immediate family members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Octohydroaminoacridine Succinate Tablet; Octohydroaminoacridine Succinate Tablet 4mg P.O. tid	Drug: Octohydroaminoacridine Succinate; Octohydroaminoacridine Succinate Tablet:4mg P.O. tid
Active Comparator: Aricept; Aricept 5mg/day P.O.	Drug: Aricept; Aricept 5mg/day, P.O.
Placebo Comparator: Placebo; Placebo P.O. tid	Drug: Placebos; Placebo Tablet: P.O. tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog)	The change of ADAS-Cog from baseline to endpoint among three arms.	26 weeks double-blind study and 28 weeks extention study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician's Interview Based Impression of Change - plus (CIBIC+)	The change of CIBIC+ from baseline to endpoint among three arms.	26 weeks double-blind study and 28 weeks extention study
Activities of Daily Living (ADL)	The change of ADL from baseline to endpoint among three arms.	26 weeks double-blind study and 28 weeks extention study
Neuropsychiatric Inventory (NPI)	The change of NPI from baseline to endpoint among three arms.	26 weeks double-blind study and 28 weeks extention study

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Changchun Huayang High-tech Co., Ltd; Jiangsu Sheneryang High-tech Co., Ltd
• Investigators: Principal Investigator: Shifu Xiao, M.D., Ph.D., Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Anticipated): September 16, 2020
• Study Completion (Anticipated): February 16, 2021

Study Registration Dates

• First Submitted: September 12, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 20, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: OHAAS-III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Other researchers should apply to the sponsor.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No