Clinical trial NCT02293915 (phase 3, status: completed)
Conditions: mild to moderate alzheimer disease, cognitive impairment
ICD codes: G31.84
Drugs: sodium oligo-mannurarate 900mg, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

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

          2. Female subjects should be postmenopausal women (menopause >24 weeks), surgically
             sterilized women or women of child bearing age who agree to take effective
             contraceptive measures during the trial. Women of child bearing age and women less
             than 24 weeks from menopause must undergo urine pregnancy test in screening period and
             result must be negative;

          3. Subjects have received education in primary school and above and are able to complete
             protocol 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 of
             Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and
             Related Disorders Association (NINCDS-ADRDA) (1984);

          6. Patients with mild to moderate disease, i.e. 11 ≤total MMSE score ≤26 (for subjects
             with 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 be
             performed, lacunar infarction lesions with a diameter larger than 2 cm ≤2, without
             lacunar infarction lesion in vital sites, such as thalamus, hippocampus, entorhinal
             cortex, paraolfactory cortex, cortex and other subcortical gray matter nuclei; MRI
             shows highest possibility of Alzheimer's disease (medial temporal lobe atrophy visual
             rating scale MTA grade ≥2);

         10. Neurological examination shows no significant sign;

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

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

        Exclusion Criteria:

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

          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's
             disease, dementia with Lewy bodies, traumatic dementia, other physical and chemical
             factors (e.g. drug poisoning, alcoholism, carbon monoxide poisoning), significant
             physical illness (e.g. hepatic encephalopathy, pulmonary encephalopathy), intracranial
             occupying 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's
             disease, epilepsy);

          5. Abnormal laboratory values: liver function (ALT, AST) > 1.5 times of upper limit of
             normal, 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 of
             normal;

          6. In screening, systolic blood pressure ≥160 mmHg or <90 mmHg, or diastolic blood
             pressure ≥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 scale
             evaluation;

          9. In screening, MRI examination shows significant focal lesions, more than 2 lacunar
             infarction lesions with a diameter >2 cm, lacunar infarction lesions in vital sites,
             such as thalamus, hippocampus, entorhinal cortex, paraolfactory cortex, cortex and
             other 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 3
             weeks prior to screening;

         14. Inability to take trial drugs according to prescription, previous non-compliance with
             prescription 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. or
             their direct relatives.