Evaluation of Safety of Contraloid Acetate in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

Study Overview
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Brief Summary
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Patients with mild cognitive impairment due to Alzheimer's disease (MCI due to AD) are at high risk to develop Alzheimer´s dementia. The therapeutic agent Contraloid has the potential to influence the chronic neurodegenerative process of AD. As Contraloid was so far only administered to healthy subjects, the rational of the proposed study is first to collect safety data in patients diagnosed with MCI due to AD, as the absorption, distribution, metabolism and excretion processes may be altered by disease, aging, comorbidities and concomitant drug therapies. Additionally, the design of a subsequent phase II study will be based on the data of this study. The results of the exploratory analyses will enable power calculations and the identification of the most useful and reliable biomarkers for the subsequent proof of concept phase II study.

Official Title
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A Single-centre, Randomized, Placebo-controlled, Double-blind, Phase 1b Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Contraloid Acetate in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

Conditions
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Mild Cognitive Impairment Due to Alzheimer's Disease

Intervention / Treatment
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* Drug: Contraloid acetate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with MCI due to AD according to DSM-V Age between 50 and 80 years (male and female) MMSE score 22-30 Written informed consent (according AMG §40 (1) 3b) Level of Aβ-oligomers: mind. 1fM CSF according to diagnosis (p-tau > 62 pg/ml, total CSF Aβ 1-42/1-40 ratio ≤ 0.055) 3 months prior to screening stable medication Females without childbearing potential Exclusion Criteria: History of seizures History of stroke or TIA Unstable medical, neurological or psychiatric condition Current treatment with one of the following substances: Typical antipsychotic or neuroleptic medication within 6 months of screening Anti-coagulation medications within 3 months of screening Chronic use of opiates or opioids (including long-acting opioid medication) within 3 months of screening Stimulant medications (amphetamine, methylphenidate preparations, or modafinil) within 1 month of screening and throughout the study Chronic use of benzodiazepines, barbiturates, or hypnotics from 3 months before screening Persons who are legally detained in an official institution Persons who may be dependent on the sponsor, the investigator or the trial site Persons without caregiver Participation in other clinical trials according to AMG (1 month before the time of this trial) Persons showing EEG abnormalities

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Contraloid acetate<br>300 mg Contraloid/participant administered orally (for 28 days) as a single daily dose. Other Name: PRI-002 | Drug: Contraloid acetate<br>* Oral administration of drug substance capsules<br>* Other names: PRI-002;|
| Placebo Comparator: Placebo<br>300 mg Placebo (Microcrystalline cellulose)/participant administered orally (for 28 days) as a single daily dose. | Drug: Placebo<br>* Oral administration of placebo without any exipients.<br>* Other names: Microcrystalline cellulose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Number of Adverse Events | From baseline (day 1) to follow-up (day 56) | 
| Safety: Number of Participants with abnormal laboratory values (urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST) | Laboratory values: urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST | From baseline (day 1) to follow-up (day 56) | 
| Safety: Number of Participants with abnormal ECG values | ECG | From baseline (day 1) to follow-up (day 56) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Peak Plasma Concentration (Cmax) | Cmax in plasma | pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 | 
| Pharmacokinetics: The time at which Cmax is observed (Tmax) | Tmax in plasma | pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 | 
| Pharmacokinetics: Terminal elimination half-life (t1/2) in plasma | t1/2 in plasma | pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 |