Safety Study of HPP854 in Subjects With Mild Cognitive Impairment or a Diagnosis of Mild Alzheimer's Disease

Exclusion Criteria

• •Blood pressure \> 160 mmHg (systolic) and \> 90 mmHg (diastolic);
• •Received HPP854 in a previous trial;
• •Participation in another clinical trial involving any marketed or investigational drug within 30 days of screening and until after the final study visit.
• •Current evidence or history within the last 3 years of a neurological or psychiatric illness that could contribute to dementia including but not limited to: anxiety, epilepsy, focal brain lesion, Parkinson's disease, seizure disorder, or head injury with loss of consciousness and alcohol or substance abuse;
• •Clinically significant cardiovascular, cerebrovascular disease, diabetic condition, hematologic, renal hepatic, pulmonary, endocrine, neurological, coagulation disorder;
• •History or presence of cancer except for non melanoma skin cancer. Subjects with a history of prostate cancer stable for \> 3 yrs with no active treatment for \> 3 years prior to Screening may be considered for eligibility;
• •Use of the following medications/therapy from 14 days before dosing until after the Final Visit: anti-cholinergic, tricyclic antidepressants, lithium, typical or atypical antipsychotic medications, anticonvulsant medications, immunosuppressive agents, oral corticosteroids, and radiotherapy;
• •HbA1C \> 6.5 % at the Screening Visit;
• •Vitamin B12 level \< 211 pg/mL at the Screening Visit;
• •Any suicidal risk determined by C-SSRS administered by a study staff member appropriately certified for administration of the scale (Baseline/Screening, Phase 1 Study Version) at Screening Visit, Day -6 or Day -1;
• •A score of 15 or more on the modified Geriatric Depression Scale (GDS); and
• •A score of 5 or more on the Hashinski Ischemic Scale (Rosen modification.
• •Contraindications of MRI including: Metallic fragments, clips or devices in the brain, eye, spinal canal, etc; Cardiac pacemakers, insulin pumps, neurostimulators, cochlear implants, etc.
• •Contraindications for blood or CSF sampling, including: Bleeding disorder or taking anticoagulants/antiplatelet, chronic active infection.