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

Study Overview
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Brief Summary
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This is a safety and tolerability study investigating the effect of HPP854 in subjects with mild cognitive impairment or a diagnosis of mild Alzheimer's disease. The study will assess the pharmacokinetic and pharmacodynamic relationships of HPP854 in plasma, pharmacodynamic relationship in cerebral spinal fluid and plasma concentration profiles for Amyloid-Beta.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Phase I , Multiple-dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally-administered HPP854 in Subjects With Mild Cognitive Impairment or a Diagnosis of Mild Alzheimer's Disease

Conditions
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Mild Alzheimer's Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: HPP854
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medical history for at least 6 months prior to screening of mild cognitive impairment with a Mini Mental State Exam (MMSE) score between 20 and 26 or diagnosis of mild Alzheimer's disease; Must be able to swallow dose of study medication; Body Mass Index (BMI) between 18.0 and 35.0; and Subject and Project Partner are willing to participate and agree to comply with all study requirements. 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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPP854<br>Oral HPP854 once a day for 28 days. | Drug: HPP854<br>* Oral, once a day for 28 days.<br>|
| Placebo Comparator: Placebo<br>Oral, placebo once a day for 28 days. | Drug: Placebo<br>* Oral, once a day for 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participant Adverse Events |  | Day 1 to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of participant plasma HPP854 concentrations |  | Day 1 to Day 30 | 
| Change in cerebrospinal fluid concentration of Amyloid-Beta |  | Day -6 to Day 35 |