A Multiple-dose, Steady-state, Double-blind, Ascending Dose, Safety, Tolerability, Pharmacokinetic Study of AL001 in Patients With Mild to Moderate Alzheimer's Disease and Healthy Adult Subjects ("MAD Study")
Phase: PHASE1
Conditions: Alzheimer's Disease, Healthy Non-elderly and Elderly Adults
Sponsor: Alzamend Neuro, Inc.

CLINICAL STUDY PROTOCOL 
 
A MULTIPLE-DOSE, STEADY-STATE, DOUBLE-BLIND, ASCENDING DOSE 
SAFETY, TOLERABILITY, PHARMACOKINETIC STUDY OF AL001 IN PATIENTS 
WITH MILD TO MODERATE ALZHEIMER’S DISEASE AND HEALTHY ADULT 
SUBJECTS (“MAD STUDY”) 
 
 
 
Version 8, Amendment 6 
 
Date: Nov. 28, 2022 
 
 
Clinical Trials.gov Identifier: NCT05363293 
 
 
 

Table of Contents
2 SYNOPSIS
2
Name of Sponsor/Company
2
Name of Finished Product
2
Name of Active Ingredient
2
Title of Study
2
Principal Investigators
2
Study Centers
2
Publication (reference)
2
Study Period
2
Phase of Development
2
Objectives
3
Study Design and Conduct
3
Subject population
4
Number of subjects (planned and analyzed)
5
Investigational product
5
Placebo
5
Study Duration and Subject Confinement
6
Criteria for Evaluation/Endpoints
6
Pharmacokinetics
6
Safety
6
Statistical methods
6
Pharmacokinetics
6
Safety Statistical Methodology
7
Summary - Conclusions
7
Pharmacokinetic Results
7
Safety Results
8
Conclusion
10
Date of Report
10
1

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 1 
2 SYNOPSIS 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
Title of Study: 
A Multiple-Dose, Steady-State, Double-Blind, Ascending Dose Safety, Tolerability, Pharmacokinetic 
Study of AL001 in Patients with Mild to Moderate Alzheimer’s Disease and Healthy Adult Subjects 
(“MAD Study”) 
Principal Investigators: 
Site 001 (Alzheimer’s Subjects [Phase 2a]):  
Kimball A. Johnson, MD, Clinical Principal Investigator 
CenExel iResearch, LLC 
Site 002 (Healthy Subjects [Phase 1]): 
Eric Sicard, MD, Clinical Principal Investigator 
Altasciences Company, Inc. 
Study Centers: 
Site 001 (Alzheimer’s Subjects [Phase 2a]):  
CenExel iResearch, LLC 
250 E. Ponce de Leon Avenue, Suite 800, Decatur, GA 30030 United States of America (USA) and 
755 Commerce Drive, Suite 100, Decatur, GA 30030 USA 
Site 002 (Healthy Subjects [Phase 1]): 
Altasciences Company Inc. 
1200 Beaumont Ave., Mount-Royal, Quebec, Canada, H3P 3P1 
Publication (reference): 
None at the time of this report 
Study Period: 
Study Initiation Date:  
2022/05/04 
Study Completion Date: 
2023/05/15 
Phase of Development: 
Phase 1 (Healthy Subjects [Canada]) 
Phase 2a (Alzheimer’s Subjects [USA]) 
2

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 2 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
Objectives: 
Primary 
• 
To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in 
Alzheimer’s disease (AD) subjects and healthy adult subjects. 
Secondary 
• 
To characterize the maximum tolerated dose (MTD) of AL001 in subjects with 
mild-to-moderate AD and healthy adult subjects. 
Exploratory 
• 
To explore the difference in pharmacokinetic (PK) profile between the non-elderly vs elderly 
subjects (healthy subjects only). 
• 
For AD subject cohorts (Cohorts 1, 2b, 3b, 4b, and 5b), determination of qualitative and 
quantitative evaluations of AD subject desirable characteristics for future Phase 2 and 3 clinical 
studies in order to: 
o facilitate recruitment into subsequent AL001 clinical trials. 
o facilitate trial-adherence to completion of study requirements including treatment adherence. 
Study Design and Conduct: 
This was a Phase 1/2a, multi-center, double-blind, placebo-controlled, randomized, multiple ascending 
dose (MAD) clinical study to determine the safety and maximum tolerated dose (MTD) of AL001 in 
subjects with mild-to-moderate AD (Food and Drug Administration Classification of Stage 2 to 4 AD) 
and healthy adult subjects. Cohorts 1, 2b, 3b, 4b, and 5b were planned to include AD subjects (between 
the ages of 50 and 80 years, inclusive) and Cohorts 2a, 3a, 4a, and 5a were planned to include healthy 
subjects (non-elderly adults between the ages of 18 to 64 years, inclusive, and healthy elderly adults 
between the ages of 65 to 80 years, inclusive).  
Each cohort was enrolled sequentially and randomized separately using a standard computerized 
method. The data from the previous cohort was deemed safe before the next sequential cohort was 
enrolled and dosing initiated. 
Cohort 1 was planned to include 8 AD subjects (6 active and 2 placebo). Each of the Cohorts 2 to 5 was 
sub-divided into 2 cohorts: Cohorts 2a, 3a, 4a, and 5a (healthy subjects) and Cohorts 2b, 3b, 4b, and 5b 
(AD subjects). 
At each dose level in Cohorts 2 to 5, the healthy subject cohort ‟a” (up to 8 subjects) was first completed 
up to Day 15 and the blinded safety (laboratory reports, AEs, tolerability) and PK data collected up to 
that point were reviewed by the Safety Review Committee. The initiation of the next dose cohort could 
be delayed up to approximately 4 weeks following the last dose of the last subject in the preceding 
cohort to allow for this process. If the dose level was endorsed as safe, the committee permitted 
progression to the AD subject cohort ‟b” at the same dose level, as well as progression to the next dose 
level of healthy subject cohort. The healthy subject cohorts proceeded to the next higher dose level 
3

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 3 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
without having to wait for the corresponding AD subject cohort to be completed and reviewed by the 
Safety Review Committee. 
Cohort 5b was planned but was not conducted due to PK-based stopping rules designed to assure that 
the assigned MTD is unlikely to result in plasma trough lithium concentrations above 1.0 mEq/L 
(healthy elderly and Alzheimer’s subjects) and 1.2 mEq/L (healthy non-elderly subjects). For salicylate, 
the maximum threshold value was 30 mg/dL for all subjects. These values pertain to subjects/patients 
with adequate renal function (estimated glomerular filtration rate [eGFR] ≥60 mL/minute/1.73 m2). 
For each cohort in which the subjects were dosed, subjects were randomized to 1 of 2 treatment groups 
in a 6:2 ratio of AL001 (active study medication) to placebo. Subjects in each of these cohorts were 
dosed 3 times daily (TID) for 14 days at the planned dose level indicated in the table below or placebo: 
Cohort 
Lithium Carbonate Equivalent Daily 
Dosing Level 
No. of AL001 
210 mg Capsules 
AL001 Daily Dose  
Cohort 1 
60% of 450 mg lithium carbonate 
3 capsules TID 
1890 mg × 14 days 
Cohort 2a/ 
Cohort 2b 
100% of 450 mg lithium carbonate 
5 capsules TID 
3150 mg × 14 days 
Cohort 3a/ 
Cohort 3b 
140% of 450 mg lithium carbonate 
7 capsules TID 
4410 mg × 14 days 
Cohort 4a/ 
Cohort 4b 
160% of 450 mg lithium carbonate 
8 capsules TID 
5040 mg × 14 days 
Cohort 5a/ 
Cohort 5b 
200% of 450 mg lithium carbonate 
10 capsules TID 
6300 mg × 14 daysa 
Abbreviation: TID = 3 times daily. 
Note: 7 mg of AL001 has the lithium content of 1 mg lithium carbonate 
a. 
Lithium dose equivalent to that routinely used for bipolar disorder type 1 treatment. 
Subject population: 
Cohorts 1, 2b, 3b, 4b, and 5b:  
Male and female adult subjects with mild-to-moderate AD, between the ages of 50 and 80 years, 
inclusive 
Cohorts 2a, 3a, 4a, and 5a:  
Healthy adult male and female subjects, between the ages of 18 to 64 years, inclusive (non-elderly) and 
between the ages 65 to 80 years, inclusive (elderly). 
4

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 4 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
Number of subjects (planned and analyzed): 
Planned for inclusion:  
• 
40 AD subjects (5 cohorts of 8 subjects each) 
• 
32 healthy subjects (4 cohorts of 8 subjects each) 
Included:  
• 
33 subjects in AD cohorts 
• 
32 subjects in healthy cohorts 
Participation discontinued: 
• 
1 subject in AD cohorts 
• 
2 subjects in healthy cohorts 
Included in the Safety Analysis Set:  
• 
33 subjects in AD cohorts 
• 
32 subjects in healthy cohorts 
Included in the PK Analysis Set:  
• 
25 subjects in AD cohorts 
• 
24 subjects in healthy cohorts 
Investigational product: 
Name: AL001 210 mg Immediate Release Capsules 
Dosage form/Route of administration: Capsule/Oral 
Regimen: TID dose administrations (8 AM, 2 PM, and 8 PM) for 14 days 
Batch number: B210312 
Placebo: 
Description: Placebo for AL001 210 mg Immediate Release Capsules 
Dosage form/Route of administration: Capsule/Oral 
Regimen: TID dose administrations (8 AM, 2 PM, and 8 PM) for 14 days 
Batch number: B220065 
5

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 5 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
Study Duration and Subject Confinement: 
The study consisted of 3 phases: 
1. Screening Phase – up to 28 days (from Days -28 to -1) 
2. Treatment Phase – 16 days (from Day -1 to Day 15): 
o Subjects were admitted to the study site on Day -1. Subjects received 14 days of TID 
dosing with assigned study medication from Days 1 to 14 and remained confined until 
Day 15. 
3. Follow-up Phase - 1 month 
o Subjects were followed up after discharge from the study site on Day 15, with a 
post-treatment clinic visit on Day 23 and a post-treatment telephone call on Day 42. 
Each subject participated in the study for up to approximately 2.5 months. 
Criteria for Evaluation/Endpoints: 
Pharmacokinetics: 
• 
Prevalence of peak salicylate plasma concentrations above 30 mg/dL 
• 
Prevalence of trough plasma lithium concentrations above 1.2 mEq/L for healthy adult subjects 
or 1.0 mEq/L for healthy elderly and AD subjects. 
Descriptive statistics for PK were represented by treatment group and compared between non-elderly 
and elderly subjects. 
Safety: 
Safety assessments included vital signs (blood pressure, heart rate, and oral body temperature), 12-lead 
electrocardiogram (ECG), physical examination, safety laboratory tests (hematology, chemistry 
[including thyroid stimulating hormone, vitamin B12, and magnesium], hemoglobin A1c (HbA1c), and 
urinalysis, and reported and observed AEs/serious AEs (SAEs)/tolerability observations including signs 
and/or symptoms of lithium and/or salicylate toxicity. 
Demographic characteristics of all screened and successfully enrolled AD subjects were documented. 
Statistical methods: 
Pharmacokinetics: 
In order to characterize the MTD of AL001 in subjects with AD and healthy subjects, descriptive 
statistics are presented by treatment group for each cohort and overall for the following: 
• 
Proportion of healthy non-elderly subjects with trough lithium concentrations >1.2 mEq/L 
• 
Proportion of subjects with peak (Cmax) salicylate concentrations >30 mg/dL 
• 
Proportion of healthy elderly and, separately, AD subjects with plasma trough measurements of 
lithium >1.0 mEq/L 
6

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 6 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
Summary statistics of the plasma concentration data were calculated for the PK population, unless 
otherwise indicated. Summary statistics were calculated for concentration at each individual time point.  
Concentration data were summarized by treatment group and compared between non-elderly and elderly 
subjects only for healthy cohorts using the following statistics: number of observations (N), arithmetic 
mean (mean), SD, geometric mean, minimum (min), median, maximum (max), and coefficient of 
variation (CV). 
For healthy subject cohorts, to explore differences in PK between non-elderly and elderly subjects, 
descriptive statistics were presented by treatment group. 
Safety Statistical Methodology: 
Descriptive statistics were used to summarize AEs, safety results and demographic variables (age, 
height, weight, and body mass index). 
Summary - Conclusions 
Pharmacokinetic Results: 
The observed AL001 MTD (the Cohort 4a/4b dosing level, 1680 mg given TID at 8 AM, 2 PM, and 
8 PM, total daily dose 5040 mg) provided lithium at a lithium carbonate equivalent dose of 240 mg TID 
(720 mg daily) or a lithium citrate oral solution or syrup (8 mEq/5 mL) equivalent dose of 4 mL TID 
(19.2 mEq daily), all under fasted conditions. With respect to salicylate, these levels of exposure can be 
justified as safe a posteriori since they are less than the maximum for prescriptive aspirin/salicylate 
indications and are to be used for a serious medical condition. There were no undue safety concerns 
identified in the AL001-ALZ02 Study and so none were considered to be related to PK exposures. The 
MTD was selected to mitigate or obviate the need for AL001 therapeutic drug monitoring (TDM) in 
targeted neurodegenerative, neurological, and neuropsychiatric conditions, at least for subjects without 
undue renal compromise. 
Under the conditions of this study, no clinically obvious or relevant lithium or salicylate PK differences 
were observed between non-elderly and elderly healthy subjects. 
There were no obvious demographic characteristics observed under the conditions of this study that can 
be used to improve future enrollments when screening subjects. 
7

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 7 
Safety Results: 
AD Subject Cohorts 
• 
No deaths or SAEs occurred during the study. No subject prematurely discontinued the study 
due to a treatment-emergent AE (TEAE). 
• 
AL001 was well tolerated in AD subjects regardless of their comorbidities and concomitant 
medications. 
• 
A total of 24 TEAEs were experienced by 12 of 25 subjects who received AL001 and 6 TEAEs 
were experienced by 4 of 8 subjects in the pooled placebo group. The proportion of AD subjects 
with TEAEs increased with increasing dose levels of AL001, with the lowest proportions of 
subjects in Cohorts 1 (14.3%; AL001 1890 mg) and 2b (16.7%; AL001 3150 mg), and the 
highest proportion observed (83.3%) in Cohorts 3b (AL001 4410 mg) and 4b (AL001 5040 mg). 
The proportion of subjects with TEAEs in the pooled placebo group (50.0%) was between that 
observed in AL001 Cohorts 2b and 3b. 
• 
All TEAEs were experienced by only 1 subject who received either AL001 or placebo, except 
headache (1 of 6 subjects [16.7%] each in Cohorts 3b and 4b) and pollakiuria (2 of 6 subjects 
[33.3%] in Cohort 4b). 
• 
No AEs of special interest were reported for AD subjects. 
• 
The majority of TEAEs were mild. (14 TEAEs across AL001 cohorts and 5 TEAEs with 
placebo). No TEAE was considered severe, life-threatening, or resulted in death. 
• 
Most TEAEs were considered unrelated to study treatment by the Investigator (13 TEAEs 
across AL001 cohorts and 6 TEAEs with placebo). 
• 
All TEAEs were resolved by the end of the study, except for 1 case each of new left bundle 
branch block (Cohort 3b/placebo) and hypopigmentation (Cohort 4b/AL001 5040 mg). 
• 
Two laboratory-associated TEAEs were reported, both of which occurred in subjects who 
received AL001. Hepatic enzyme increased was of mild intensity, considered possibly related to 
AL001 by the Investigator, and was resolved at the end of the study. Blood thyroid stimulating 
hormone increased was of moderate intensity and considered unrelated to AL001 by the 
Investigator. This subject had an ongoing medical history of hypothyroidism and the TEAE 
resolved after adjusting the dose of levothyroxine. 
• 
One ECG-associated TEAE, bundle branch block left, was reported for 1 subject in Cohort 3b 
(placebo). The TEAE was mild, considered not related to study drug administration by the 
Investigator, and was ongoing at last contact. 
• 
No clinically significant abnormal findings in vital signs, ECGs, or physical examinations were 
noted during the study. 
Healthy Subject Cohorts 
• 
No deaths or SAEs occurred during the study. No subject prematurely discontinued the study 
due to a TEAE. 
• 
AL001 was well tolerated in healthy elderly and non-elderly subjects. 
• 
A total of 76 TEAEs were experienced by 16 of 24 subjects who received AL001 and 21 TEAEs 
were experienced by 5 of 8 subjects in the pooled placebo group. The proportion of healthy 
subjects with TEAEs was comparable across cohorts and pooled placebo treatment groups, with 
8

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 8 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
the highest proportion (83.3%) observed in AL001 Cohorts 3a (AL001 4410 mg) and 5a 
(AL001 6300 mg), compared to a proportion of 62.5% for the pooled placebo group. 
• 
The most commonly reported TEAE across all treatments was constipation, experienced by 1 of 
the 6 subjects (16.7%) in Cohort 2a, 4 of the 6 subjects (66.7%) in Cohort 3a, and 2 of the 
6 subjects (33.3%) each in Cohorts 4a and 5a, and 3 of the 8 subjects (37.5%) in the pooled 
placebo group. 
• 
The overall proportion of subjects with TEAEs appeared higher for non-elderly subjects (75%) 
compared to elderly subjects (56.3%). 
• 
For combined healthy subjects, AEs of special interest were reported with the highest proportion 
of subjects at the highest dose level in Cohort 5a (50.0%). 
• 
The majority of TEAEs were mild (72 TEAEs across AL001 treatments and 20 TEAEs with 
placebo). Three moderate TEAEs (2 TEAEs with AL001 and 1 TEAE with placebo) and 
2 severe TEAEs (with AL001) were also reported. The severe TEAEs were alanine 
aminotransferase increased (Cohort 3a/AL001 4410 mg) and hepatic enzyme increased 
(Cohort 5a/AL001 6300 mg). Both severe TEAEs were considered by the Investigator to be 
possibly related to AL001 and were resolved at the end of the study. No TEAEs were 
considered life-threatening or resulted in death. 
• 
The majority of TEAEs were considered to be related to study treatment (65 TEAEs across 
AL001 and 16 TEAEs with placebo) by the Investigator. 
• 
All TEAEs were resolved at the end of the study, except for acne (Cohort 5a/placebo), rash and 
pruritus (Cohort 5a/AL001 6300 mg), and tinnitus (Cohort 5a/AL001 6300 mg), each in 
1 subject. 
• 
Four laboratory-associated TEAEs were reported, all of which were resolved at the end of the 
study. Alanine aminotransferase increased and hepatic enzyme increased were both of severe 
intensity and considered possibly related to AL001 by the Investigator. Another TEAE of 
hepatic enzyme increased was of moderate intensity and was considered possibly related to 
AL001 by the Investigator. A TEAE of mild hypothyroidism was considered possibly related to 
placebo by the Investigator. One additional TEAE of urinary tract infection was reported in the 
setting of clinically significant elevated urine protein; this TEAE was of mild intensity and was 
considered unrelated to AL001 by the Investigator. 
• 
No clinically significant abnormal findings in vital signs, ECGs, or physical examinations were 
noted during the study. 
9

Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
 
 
Page 9 
Name of Sponsor/Company: 
Alzamend Neuro, Inc. 
Individual Study Table 
Referring to Part of the 
Dossier 
 
Volume: 
 
Page: 
(For National 
Authority Use Only) 
Name of Finished Product: 
AL001 
Name of Active Ingredient: 
Lithium salicylate/L-proline cocrystal 
Conclusion: 
• 
Under the conditions of this study, multiple dose administrations of AL001 was well tolerated in 
healthy elderly and non-elderly subjects, and in subjects with AD, regardless of their 
comorbidities and concomitant medications. 
• 
The observed AL001 MTD (1680 mg given TID at 8 AM, 2 PM, and 8 PM, total daily dose 
5040 mg) provided lithium at a lithium carbonate equivalent dose of 240 mg TID (720 mg 
daily) or a lithium citrate oral solution or syrup (8 mEq/5 mL) equivalent dose of 4 mL TID 
(19.2 mEq daily), all under fasted conditions. The MTD was selected to mitigate or obviate the 
need for TDM in targeted neurodegenerative, neurological, and neuropsychiatric conditions, at 
least for subjects without undue renal compromise. 
• 
With respect to salicylate, these levels of exposure can be justified as safe a posteriori since 
they are less than the maximum for prescriptive aspirin/salicylate indications and are to be used 
for a serious medical condition. 
• 
No clinically obvious or relevant lithium or salicylate PK differences were observed between 
non-elderly and elderly healthy subjects, under the conditions of this study. 
• 
No obvious demographic characteristics were observed under the conditions of this study that 
can be used to improve successful future enrollments when screening subjects. 
Date of Report: 2024/10/30 
 
 
10