An Efficacy and Safety Study of Sodium Oligo-mannurarate (GV-971) Capsule for the Treatment of Alzheimer's Disease

Inclusion Criteria:

1. Aged 50-85 years (inclusive), no gender limitation;

2. Female subjects should be postmenopausal women (menopause >24 weeks), surgicallysterilized women or women of child bearing age who agree to take effectivecontraceptive measures during the trial. Women of child bearing age and women lessthan 24 weeks from menopause must undergo urine pregnancy test in screening period andresult must be negative;

3. Subjects have received education in primary school and above and are able to completeprotocol specified cognitive ability test and other tests;

4. Impaired memory for at least 12 months, with a tendency of progressive aggravation;

5. Meet diagnostic criteria of probable AD according to National Institute ofNeurological and Communicative Disorders and Stroke and the Alzheimer's Disease andRelated Disorders Association (NINCDS-ADRDA) (1984);

6. Patients with mild to moderate disease, i.e. 11 ≤total MMSE score ≤26 (for subjectswith primary school education, 11 ≤total MMSE score ≤22);

7. Total Hachinski Ischemia Scale (HIS) score ≤4 ;

8. Total Hamilton Depression Scale/17-item (HAMD) score ≤10;

9. In screening, cranial MRI plain scan and oblique coronal hippocampus scan must beperformed, lacunar infarction lesions with a diameter larger than 2 cm ≤2, withoutlacunar infarction lesion in vital sites, such as thalamus, hippocampus, entorhinalcortex, paraolfactory cortex, cortex and other subcortical gray matter nuclei; MRIshows highest possibility of Alzheimer's disease (medial temporal lobe atrophy visualrating scale MTA grade ≥2);

10. Neurological examination shows no significant sign;

11. Subjects should have stable, reliable caregivers, or at least have frequent contactwith caregivers (at least 4 days every week, at least 2 h every day), and caregiverswill help patients in participation in this study. Caregivers must accompany subjectsto participate in study visits and have sufficient interaction and communication withsubjects, so as to provide valuable information on NPI, ADCS-ADL, CIBIC-plus scales.

12. Before implementation of any protocol related procedure or examination, subjects mustsign the written informed consent form. If subjects can not sign due to limitedcognition, legal guardians should sign on behalf of subjects and meanwhile, legalguardians should also sign the informed consent form.

Exclusion Criteria:

1. Participate in another clinical trial within 30 days prior to initiation of thisstudy;

2. Pregnant or nursing women;

3. Dementia due to other causes: vascular dementia, central nervous system infection (e.g. AIDS, syphilis), Creutzfeldt-Jakob disease, Huntington's chorea, Parkinson'sdisease, dementia with Lewy bodies, traumatic dementia, other physical and chemicalfactors (e.g. drug poisoning, alcoholism, carbon monoxide poisoning), significantphysical illness (e.g. hepatic encephalopathy, pulmonary encephalopathy), intracranialoccupying lesion (e.g. subdural hematoma, brain tumor), endocrine disorders (e.g.thyroid disease, parathyroid disease) and dementia caused by vitamin or other factors;

4. Previous nervous system disorders (including stroke, optic neuromyelitis, Parkinson'sdisease, epilepsy);

5. Abnormal laboratory values: liver function (ALT, AST) > 1.5 times of upper limit ofnormal, Cr > 1.5 times of upper limit of normal, white blood cell count, platelet,hemoglobin below the lower limit of normal, blood glucose >1.5 times of upper limit ofnormal;

6. In screening, systolic blood pressure ≥160 mmHg or <90 mmHg, or diastolic bloodpressure ≥100 mmHg or <60 mmHg;

7. Unstable or severe cardiac, pulmonary, hepatic, renal or hematopoietic disease (including unstable angina, uncontrolled asthma, active gastric bleeding and cancer),after 10 min rest, resting heart rate <55 bpm;

8. Visual or hearing disorder, preventing completion of neuropsychological test and scaleevaluation;

9. In screening, MRI examination shows significant focal lesions, more than 2 lacunarinfarction lesions with a diameter >2 cm, lacunar infarction lesions in vital sites,such as thalamus, hippocampus, entorhinal cortex, paraolfactory cortex, cortex andother subcortical gray matter nuclei; Fazekas scale for white matter lesions at ≥grade 3;

10. Alcohol abuse or drug abuse;

11. Patients with psychosis, including severe depression;

12. Patients who are using drugs for Alzheimer's disease which can not be stopped;

13. Use of heparin, Propylene Glycol Mannurate Sulfate or Alginric Sodium Diester within 3weeks prior to screening;

14. Inability to take trial drugs according to prescription, previous non-compliance withprescription or possibility of non-compliance with study treatment in the trial;

15. Investigators consider subjects can not complete this study;

16. Subjects in the phase II trial of the study drug;

17. Subjects are investigators participating in this study or their direct relatives,staff of Quintiles (Shanghai) or Shanghai Greenvalley Pharmaceutical Co., Ltd. ortheir direct relatives.