"MAD": Multiple Ascending Dose Safety, Tolerability, Pharmacokinetic Study of AL001 in Patients With Alzheimer's Disease
Study Details
Study Description
Brief Summary
This is a Phase 2a, single-center, placebo-controlled, double-blinded, randomized, multiple ascending dose (MAD) clinical trial to determine the safety and maximum tolerated dose of AL001. Approximately 40 participants will be randomly assigned to receive study drug (active AL001) or placebo. The study consists of a 4-week screening period, a 14-day treatment period, and a 42-day follow-up period.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a Phase 2a, single-center, placebo-controlled, double-blind, randomized, multiple ascending dose (MAD) clinical trial to determine the safety and maximum tolerated dose (MTD) of AL001, a crystal engineered lithium-salicylate-proline lithium delivery product that in nonclinical studies was shown to enhance and prolong the pharmacokinetic (PK) profile of lithium in the brain with enhanced efficacy potential in Alzheimer's models compared to lithium carbonate.
A maximum of approximately 40 participants will be enrolled. Participants will be randomly assigned to receive study drug (active AL001) or placebo in a ratio of 6:2, respectively, with 8 patients in each dosing cohort. The study will consist of a screening period (Days -28 to -2), a 14-day treatment period, and a 42-day follow-up period.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Multiple Ascending Dose AL001 Participants will be randomized to receive AL001. When adequate safety data are available, a review will be done for all participants to make a dose-escalation or dose and/or regimen modification decision. This will be repeated for each cohort. AL 001 administered per os on Day 1 and according to dosing schedule. |
Drug: AL 001
a crystal engineered lithium-salicylate-proline lithium delivery product
|
| Placebo Comparator: Placebo Participants will receive AL001- matching placebo. Administered per os starting on Day 1 and according to dosing schedule. |
Drug: Placebo
matching placebo formulation
|
Outcome Measures
Primary Outcome Measures
- Number of participants with serious AEs, TEAEs that lead to premature discontinuation, abnormal laboratory test results, abnormal ECG readings. [a 14-day treatment period]
To evaluate the safety and tolerability of AL001 in patients with adverse event(s), AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: Proportion of patients with treatment-emergent adverse events (TEAEs) Proportion of patients with serious AEs Proportion of patients with TEAEs that lead to premature discontinuation Proportion of patients with abnormal values for each safety laboratory test (change from baseline) Proportion of patients with abnormal values for each Electrocardiogram (ECG) parameter (change from baseline in standard 12-lead ECG parameters)
- Number of participants with serious AEs, TEAEs that lead to premature discontinuation, abnormal laboratory test results, abnormal ECG readings. [a 42-day follow-up period]
To evaluate the safety and tolerability of AL001 in patients with adverse event(s), AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: Proportion of patients with treatment-emergent adverse events (TEAEs) Proportion of patients with serious AEs Proportion of patients with TEAEs that lead to premature discontinuation Proportion of patients with abnormal values for each safety laboratory test (change from baseline) Proportion of patients with abnormal values for each ECG parameter (change from baseline in standard 12-lead ECG parameters)
Secondary Outcome Measures
- Maximum Tolerated Dose of AL001 in patients with Alzheimers Disease [a 14-day treatment period]
To characterize the MTD of AL001 in patients with AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: Proportion of patients with plasma trough measurements of lithium > 1.2 mEq/L Proportion of patients with plasma maximum concentration (Cmax) measurements for salicylate > 30 mg/dL
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Availability of medical history to provide information about the cognitive and functional level of the participant and of a qualified source such as the caregiver willing and able to provide information about the cognitive and functional level of the participant
-
Males (non-vasectomized and vasectomized) must agree to use barrier contraception during the study until after Study Day 42
-
Females must meet criteria if childbearing for contraception or be non-childbearing
-
Clinical diagnosis of dementia (neurocognitive disorder) by a qualified clinician based on the DSM-V criteria:
-
Considered AD Stage 2, 3, or 4 based on the FDA classification
-
Mini-Mental State Examination (MMSE) score between 16 and 26, inclusive, at Screening
-
Patient's health is judged adequate to participate in this clinical study by the Investigator
Exclusion Criteria:
-
Female who is breastfeeding, pregnant, planning to become pregnant during study
-
Kidney disease (eGFR <50 mL/minute/1.73 m2)
-
History of untreated thyroid dysfunction that may be independently associated with cognitive impairment
-
Uncontrolled tachy/brady arrhythmias, atrial fibrillation or coronary heart failure
-
Any medical condition that in the Investigator's judgement would affect patient safety and scientific integrity of the studySystemic related exclusions:
-
History of allergy or AE(s) associated with the study treatments, including lithium and salicylates
-
Pre-existing peptic ulcer, hemorrhagic gastritis, or duodenitis
-
Magnetic resonance imaging (MRI)-related exclusion criteria
-
Treatment with haloperidol
-
Hyponatremia
-
Suspected of having or at risk for Brugada Syndrome
-
Prescribed or over-the-counter use of a salicylate-containing product other than low dose aspirin for cardioprotection (eg, aspirin, bismuth sub-salicylate, salicylazosulfapyridine [sulfasalazine]) from 1 week before first dose to 1 week after last dosing; treatment with haloperidol
-
Aspirin/nasal polyposis/asthma syndrome
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | iResearch Atlanta & iResearch Savannah | Decatur | Georgia | United States | 30030 |
Sponsors and Collaborators
- Alzamend Neuro, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AL001-ALZ02