Trial Outcomes & Findings for Multiple Ascending Dose Safety, Tolerability, PK Study of AL001 in Alzheimer's Disease Patients & Healthy Adult Subjects (NCT NCT05363293)

Last Updated: 2025-05-14

Results Overview

To evaluate the safety and tolerability of AL001 in healthy subjects and patients 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 Electrocardiogram (ECG) parameter (change from baseline in standard 12-lead ECG parameters) For all analyses, placebo-treated subjects from each Cohort were combined (pooled) to provide a composite placebo group for all comparisons. Adverse event profiles for all treated subjects were benign as were placebo-treated subjects. No further statistical analyses were therefore appropriate.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

65 participants

Primary outcome timeframe

42 days with a 14-day treatment period

Results posted on

2025-05-14

Participant Flow

There were no pre-specified comparisons between healthy controls and AD patients.

Participant milestones

Participant milestones
Measure	Multiple Ascending Doses of AL001 - Cohort 1 AD-only participants (no normal healthy subjects) were randomized to receive AL001. When adequate safety data were available, a review was done for all participants to make a dose-escalation or dose and/or regimen modification decision. This was repeated for each cohort. A total of 8 cohorts received 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 included 6 AD subjects only (7 were randomized because 1 subject voluntarily withdrew before dosing); 6 active AD subjects (as per randomization code) received 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 2a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 2b The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2b (6 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 3a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 3a: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 3b The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3b (6 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 4a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 4b The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4b (6 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 5a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 5 was planned to be divided into 2 sub-cohorts: Cohort 5a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 5b (8 AD subjects). Per randomization, there were 6 active normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5a: 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Combined Placebo Group 2 subjects were randomized to receive matching placebo (no active drug) concurrently with each of the 8 treatment cohorts. A total of 16 subjects receiving placebo were combined in 1 group.
Overall Study STARTED	7	6	6	6	6	6	6	6	16
Overall Study COMPLETED	6	6	6	6	6	6	6	6	16
Overall Study NOT COMPLETED	1	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Multiple Ascending Doses of AL001 - Cohort 1 AD-only participants (no normal healthy subjects) were randomized to receive AL001. When adequate safety data were available, a review was done for all participants to make a dose-escalation or dose and/or regimen modification decision. This was repeated for each cohort. A total of 8 cohorts received 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 included 6 AD subjects only (7 were randomized because 1 subject voluntarily withdrew before dosing); 6 active AD subjects (as per randomization code) received 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 2a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 2b The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2b (6 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 3a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 3a: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 3b The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3b (6 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 4a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 4b The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4b (6 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 5a The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 5 was planned to be divided into 2 sub-cohorts: Cohort 5a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 5b (8 AD subjects). Per randomization, there were 6 active normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5a: 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 5b Subjects for Cohort 5b (6 AD subjects) were not enrolled because the Safety Committee invoked study stopping rules. Per randomization, there were 6 active normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5b was not dosed. Subjects would have been dosed at 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Combined Placebo Group 2 subjects were randomized to receive matching placebo (no active drug) concurrently with each of the 8 treatment cohorts. A total of 16 subjects receiving placebo were combined in 1 group.
Overall Study Withdrawal by Subject	1	0	0	0	0	0	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Multiple Ascending Doses of AL001- Cohort 1 (1890 mg AL001/d, 630mg TID ×14 Days) n=7 Participants AD-only participants (no normal healthy subjects) were randomized to receive AL001. When adequate safety data were available, a review was done for all participants to make a dose-escalation or dose and/or regimen modification decision. This was repeated for each cohort. A total of 8 cohorts received 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 included 6 AD subjects only (7 were randomized because 1 subject voluntarily withdrew before dosing); 6 active AD subjects (as per randomization code) received the following treatment: • 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 2a (3150 mg AL001/d, 1050mg TID × 14 Days) n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 2b (6 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 2b (3150 mg AL001/d, 1050mg TID × 14 Days) n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 3a (4410 mg AL001/d, 1470mg TID × 14 Days) n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 3b (6 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 3a: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 3b (4410 mg AL001/d, 1470mg TID × 14 Days) n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 3b (6 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 4a (5040 mg AL001/d, 1680mg TID × 14 Days) n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 4b (6 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 4b (5040 mg AL001/d, 1680mg TID × 14 Days) n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 4b (6 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort: • Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 5a (6300 mg AL001/d, 2100mg TID × 14 Days) n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 5 was planned to be divided into 2 sub-cohorts: Cohort 5a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 5b (6 AD subjects). Per randomization, there were 6 active normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5a: 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Multiple Ascending Doses of AL001 - Cohort 5b (6300 mg AL001/d, 2100mg TID × 14 Days) Subjects for Cohort 5b (6 AD subjects) were not enrolled because the Safety Committee invoked study stopping rules due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5b was not dosed. Subjects would have been dosed at 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product.	Combined Placebo Group n=16 Participants 2 subjects were randomized to receive matching placebo (no active drug) concurrently with each of the 8 treatment cohorts. A total of 16 subjects receiving placebo were combined in 1 group.	Total n=65 Participants Total of all reporting groups
Age, Customized	63.1 years n=93 Participants	65.4 years n=4 Participants	65.4 years n=27 Participants	57.5 years n=483 Participants	57.5 years n=36 Participants	58.8 years n=10 Participants	58.8 years n=115 Participants	57.3 years n=40 Participants	—	59.4 years n=62 Participants	60.2 years n=95 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	1 Participants n=483 Participants	4 Participants n=36 Participants	2 Participants n=10 Participants	4 Participants n=115 Participants	2 Participants n=40 Participants	—	12 Participants n=62 Participants	34 Participants n=95 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	5 Participants n=483 Participants	2 Participants n=36 Participants	4 Participants n=10 Participants	2 Participants n=115 Participants	4 Participants n=40 Participants	—	4 Participants n=62 Participants	31 Participants n=95 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	—	0 Participants n=62 Participants	0 Participants n=95 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	—	0 Participants n=62 Participants	0 Participants n=95 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	—	0 Participants n=62 Participants	0 Participants n=95 Participants
Race (NIH/OMB) Black or African American	6 Participants n=93 Participants	0 Participants n=4 Participants	4 Participants n=27 Participants	2 Participants n=483 Participants	4 Participants n=36 Participants	0 Participants n=10 Participants	5 Participants n=115 Participants	0 Participants n=40 Participants	—	7 Participants n=62 Participants	28 Participants n=95 Participants
Race (NIH/OMB) White	1 Participants n=93 Participants	6 Participants n=4 Participants	2 Participants n=27 Participants	4 Participants n=483 Participants	2 Participants n=36 Participants	6 Participants n=10 Participants	1 Participants n=115 Participants	6 Participants n=40 Participants	—	9 Participants n=62 Participants	37 Participants n=95 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	—	0 Participants n=62 Participants	0 Participants n=95 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	—	0 Participants n=62 Participants	0 Participants n=95 Participants
Ratio of Plasma Lithium trough >1.0mEq/L or plasma salicylate peak concentrations >30mg/dL	0 ratio n=93 Participants	0 ratio n=4 Participants	0 ratio n=27 Participants	0 ratio n=483 Participants	0 ratio n=36 Participants	0 ratio n=10 Participants	0 ratio n=115 Participants	0 ratio n=40 Participants	—	0 ratio n=62 Participants	0 ratio n=95 Participants

PRIMARY outcome

Timeframe: 42 days with a 14-day treatment period

Population: All subjects in the Randomized Analysis Set who received any dose of the study drug. This analysis set was used for all safety analyses.

Outcome measures

Outcome measures
Measure	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 n=6 Participants AD-only participants (no normal healthy subjects) were randomized to receive AL001. When adequate safety data were available, a review was done for all participants to make a dose-escalation or dose and/or regimen modification decision. This was repeated for each cohort. A total of 8 cohorts received 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 included 8 AD subjects only (9 were randomized because 1 subject voluntarily withdrew before dosing); 6 active and 2 placebo AD subjects (as per randomization code) received 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 3a: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 5 was planned to be divided into 2 sub-cohorts: Cohort 5a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 5b (8 AD subjects). Per randomization, there were 6 active and 2 placebo normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5a: 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). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b Subjects for Cohort 5b (8 AD subjects) were not enrolled because the Safety Committee invoked study stopping rules due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5b was not dosed. Subjects would have been dosed at 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation.	Multiple Ascending Doses of AL001 - Pooled Placebo Group n=16 Participants This is a Cohort which is a composite of all 16 placebo-treated participants derived from all recruited Cohorts. Placebo: matching placebo formulation
Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. Serious AEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. TEAEs that lead to premature discontinuation	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	0 Participants
Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. Abnormal values for safety laboratory tests (change from baseline)	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—	0 Participants
Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. abnormal ECG parameters (change from baseline)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	0 Participants
Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. No Adverse Events observed	6 Participants	6 Participants	6 Participants	5 Participants	6 Participants	5 Participants	6 Participants	6 Participants	—	16 Participants

SECONDARY outcome

Timeframe: 42 days with a 14-day treatment period

Population: All subjects in the Safety Analysis Set who received AL001 and had a trough measurement for lithium.

To characterize the MTD of AL001 in all subjects treated with AL001: • Proportion of subjects in each Cohort with plasma trough measurements of lithium \> 1.0 mEq/L. Subjects above these values invoke stopping rules for subsequent cohort enrollment.

Outcome measures

Outcome measures
Measure	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 n=6 Participants AD-only participants (no normal healthy subjects) were randomized to receive AL001. When adequate safety data were available, a review was done for all participants to make a dose-escalation or dose and/or regimen modification decision. This was repeated for each cohort. A total of 8 cohorts received 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 included 8 AD subjects only (9 were randomized because 1 subject voluntarily withdrew before dosing); 6 active and 2 placebo AD subjects (as per randomization code) received 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 3a: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 5 was planned to be divided into 2 sub-cohorts: Cohort 5a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 5b (8 AD subjects). Per randomization, there were 6 active and 2 placebo normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5a: 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). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b Subjects for Cohort 5b (8 AD subjects) were not enrolled because the Safety Committee invoked study stopping rules due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5b was not dosed. Subjects would have been dosed at 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation.	Multiple Ascending Doses of AL001 - Pooled Placebo Group n=16 Participants This is a Cohort which is a composite of all 16 placebo-treated participants derived from all recruited Cohorts. Placebo: matching placebo formulation
Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0.167 Proportion of Subjects	—	0 Proportion of Subjects

SECONDARY outcome

Timeframe: 42 days with a 14-day treatment period

Population: All subjects in the Safety Analysis Set who received AL001 and had a Cmax measurement for salicylate.

To characterize the MTD of AL001 in all subjects: • Proportion of all subjects with plasma maximum concentration (Cmax) measurements for salicylate \> 30 mg/dL

Outcome measures

Outcome measures
Measure	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 n=6 Participants AD-only participants (no normal healthy subjects) were randomized to receive AL001. When adequate safety data were available, a review was done for all participants to make a dose-escalation or dose and/or regimen modification decision. This was repeated for each cohort. A total of 8 cohorts received 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 included 8 AD subjects only (9 were randomized because 1 subject voluntarily withdrew before dosing); 6 active and 2 placebo AD subjects (as per randomization code) received 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 3a: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 4b (8 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active and 2 placebo subjects in each cohort: • Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a n=6 Participants The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated. Cohort 5 was planned to be divided into 2 sub-cohorts: Cohort 5a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 5b (8 AD subjects). Per randomization, there were 6 active and 2 placebo normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5a: 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). AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation	Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b n=16 Participants Subjects for Cohort 5b (8 AD subjects) were not enrolled because the Safety Committee invoked study stopping rules due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations. • Cohort 5b was not dosed. Subjects would have been dosed at 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) AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product Placebo: matching placebo formulation.	Multiple Ascending Doses of AL001 - Pooled Placebo Group This is a Cohort which is a composite of all 16 placebo-treated participants derived from all recruited Cohorts. Placebo: matching placebo formulation
Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0 Proportion of Subjects	0.167 Proportion of Subjects	0 Proportion of Subjects	—

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	AD in Cohort 1 n=6 participants at risk Subject w/AD randomized to 1890 mg AL001 daily ×14 days, given as 3 × 210 mg AL001 capsules TID.	AD on Cohort 2 n=6 participants at risk Subject w/AD randomized to 3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID.	AD in Cohort 3 n=6 participants at risk Subject w/AD randomized to 4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID.	AD in Cohort 4 n=6 participants at risk Subject w/AD randomized to 5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID.	Healthy Subjects in Cohort 2 n=6 participants at risk Healthy Subject randomized to 3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID.	Healthy Subjects in Cohort 3 n=6 participants at risk Healthy Subject randomized to 4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID.	Healthy Subjects in Cohort 4 n=6 participants at risk Healthy Subject randomized to 5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID.	Healthy Subjects in Cohort 5 n=6 participants at risk Healthy Subject randomized to 6300 mg AL001 daily × 14 days - lithium dose equivalent to that used for bipolar/affective disorders, given as 10 × 210 mg AL001 capsules TID.	AD Subjects on Placebo n=8 participants at risk Subjects w/AD randomized to Placebo across all Cohorts	Healthy Subjects on Placebo n=8 participants at risk Healthy Subjects randomized to Placebo in all Cohorts
Gastrointestinal disorders Gastrointestinal	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 4 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	66.7% 4/6 • Number of events 7 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 5 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	66.7% 4/6 • Number of events 11 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	37.5% 3/8 • Number of events 8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Nervous system disorders Nervous System	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 3 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 4 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Investigations Investigations	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	50.0% 3/6 • Number of events 3 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	50.0% 3/6 • Number of events 3 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Renal and urinary disorders Renal and Urinary	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Skin and subcutaneous tissue disorders Skin	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	25.0% 2/8 • Number of events 3 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Injury, poisoning and procedural complications Procedural complications	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Respiratory, thoracic and mediastinal disorders Respiratory	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 4 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Psychiatric disorders Psychiatric	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	33.3% 2/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Musculoskeletal and connective tissue disorders Musculoskeletal	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 2 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Ear and labyrinth disorders Ear Labyrinth	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	16.7% 1/6 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)
Endocrine disorders Endocrine	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/6 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	0.00% 0/8 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)	12.5% 1/8 • Number of events 1 • 42 days with a 14 day treatment period per cohort (phone call follow-up on day 42 to confirm safety)

Additional Information

Eve Del Rio, MD, PhD

Alzamend Inc.

Phone: 9736993847

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60