Multiple Ascending Dose Safety, Tolerability, PK Study of AL001 in Alzheimer's Disease Patients & Healthy Adult Subjects

Phase 1

Completed

• Conditions: Alzheimer's Disease; Healthy Non-elderly and Elderly Adults
• Interventions: Drug: AL 001; Drug: Placebo

• Registration Number: NCT05363293
• Lead Sponsor: Alzamend Neuro, Inc.

Brief Summary

This is a Phase 1/2a, multi-center, placebo-controlled, double-blinded, randomized, multiple ascending dose (MAD) clinical trial to determine the safety and maximum tolerated dose of AL001. Up to 72 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.

Detailed Description

This is a Phase 1/2a, multi-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 72 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. Cohorts 2a, 3a, 4a and 5a will involve 1:1 healthy non-elderly and elderly subjects; cohorts 1, 2b, 3b, 4b and 5b will involve Alzheimer's subjects. 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 Timeline

• Study First Submitted: 2022-04-27
• Study First Submitted QC: 2022-05-02
• Study Start: 2022-05-04
• Study First Posted: 2022-05-05
• Status Verified: 2023-01
• Primary Completion: 2023-04-14
• Study Completion: 2023-05-15
• Last Update Submitted: 2023-07-19
• Last Update Posted: 2023-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3	Placebo	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 3 will be sub-divided into 2 cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 3a and 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID)
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3	AL 001	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 3 will be sub-divided into 2 cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 3a and 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID)
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1	Placebo	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. A total of 9 cohorts will receive 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 will include 8 AD subjects. In this cohort, 6 active and 2 placebo AD subjects (as per randomization code) will receive the following treatment or placebo: • Cohort 1: 60% of 450 mg lithium carbonate equivalent of AL001 (1890 mg AL001 daily ×14 days, given as 3 × 210 mg AL001 capsules TID)
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2	Placebo	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 2 will be sub-divided into 2 cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 2a and 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID).
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4	Placebo	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 4 will be sub-divided into 2 cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 4a and 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID)
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1	AL 001	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. A total of 9 cohorts will receive 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 will include 8 AD subjects. In this cohort, 6 active and 2 placebo AD subjects (as per randomization code) will receive the following treatment or placebo: • Cohort 1: 60% of 450 mg lithium carbonate equivalent of AL001 (1890 mg AL001 daily ×14 days, given as 3 × 210 mg AL001 capsules TID)
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5	Placebo	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 5 will be sub-divided into 2 cohorts: Cohort 5a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 5b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 5a and 5b: 200% of 450 mg lithium carbonate equivalent of AL001 (6300 mg AL001 daily × 14 days - lithium dose equivalent to that used for bipolar/affective disorders, given as 10 × 210 mg AL001 capsules TID)
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4	AL 001	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 4 will be sub-divided into 2 cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 4a and 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID)
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2	AL 001	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 2 will be sub-divided into 2 cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 2a and 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID).
Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5	AL 001	The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 5 will be sub-divided into 2 cohorts: Cohort 5a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 5b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 5a and 5b: 200% of 450 mg lithium carbonate equivalent of AL001 (6300 mg AL001 daily × 14 days - lithium dose equivalent to that used for bipolar/affective disorders, given as 10 × 210 mg AL001 capsules TID)

Primary Outcome Measures

Name	Time	Method
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 participants with adverse event(s), AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: Proportion of participants with treatment-emergent adverse events (TEAEs); * Proportion of participants with serious AEs; * Proportion of participants with TEAEs that lead to premature discontinuation; * Proportion of participants with abnormal values for each safety laboratory test (change from baseline); * Proportion of participants with abnormal values for each ECG parameter (change from baseline in standard 12-lead ECG parameters)

Secondary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of AL001 in healthy subjects and patients with Alzheimers Disease	a 14-day treatment period	To characterize the MTD of AL001 in healthy subjects and in patients with AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: * Proportion of healthy non-elderly adult subjects and healthy elderly subjects/patients with plasma trough measurements of lithium \> 1.0 and \>1.2 mEq/L, respectively; * Proportion of healthy subjects and patients with plasma maximum concentration (Cmax) measurements for salicylate \> 30 mg/dL

Trial Locations

Locations (2)

Altasciences; 🇨🇦 Mount-Royal, Quebec, Canada

CenExel iResearch, LLC; 🇺🇸 Decatur, Georgia, United States