Clinical trial NCT05363293
Conditions: Alzheimer's Disease Healthy Non-elderly and Elderly Adults
Sponsor: Alzamend Neuro, Inc.
Start date: 2022-05-04; Completion date: 2023-05-15
Enrollment: 65 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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. Placebos will be pooled and regarded as a comparative cohort for safety.

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.

Arms: arm 1: 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) arm 2: The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated.

Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults). Per randomization, there will be 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). arm 3: 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) arm 4: The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated.

Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults). Per randomization, there will be 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) arm 5: The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated.

Cohort 5a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults). Per randomization, there will be 6 active and 2 placebo subjects in each cohort:

• 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) arm 6: The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated.

Cohort 2b (8 AD subjects). Per randomization, there will be 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). arm 7: The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated.

Cohort 3b (8 AD subjects). Per randomization, there will be 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) arm 8: The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated.

Cohort 4b (8 AD subjects). Per randomization, there will be 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) arm 9: The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated.

Cohort 5b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort:

• Cohort 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).
Interventions: intervention 1: AL001 intervention 2: Placebo
Intervention descriptions: intervention 1: a crystal engineered lithium-salicylate-proline lithium delivery product intervention 2: matching placebo formulation

Protocol documents:
Prot_002.pdf: 
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

SAP_003.pdf: 
 
STATISTICAL ANALYSIS PLAN 
Protocol No. AL001-ALZ02 
 
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”) 
 
AltaSciences Project No. ALZ-P9-319 
 
 
Version 1.1 (Final) 
 
Date: 05 May, 2023 
 
 
Clinical Trials.gov Identifier: NCT05363293 
 
 
 


Clinical Study Report No. AL001-ALZ02 
Altasciences Project No. ALZ-P9-319 
16.1.9 
Documentation of Statistical Methods 
Statistical Analysis Plan – Final Version 1.1 
Statistical Analysis Plan – Final Version 1.0 
1


STATISTICAL ANALYSIS PLAN 
For: 
Alzamend Neuro, Inc. 
PROTOCOL No. AL001-ALZ02 
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”) 
Altasciences Project No. ALZ-P9-319 
Prepared by: 
Altasciences Company Inc. 
575 Armand-Frappier Boulevard 
Laval, Quebec 
Canada, H7V 4B3 
Version: Final 1.1 
Date: 2023-05-05 
2


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 2 of 28 
We have carefully read this statistical analysis plan and agree it contains the necessary information 
required to handle the statistical analysis of study data. 
Riddhi Thakkar 
Biostatistician II, Altasciences 
Date 
On behalf of the Sponsor: 
Eve del Rio, MD, PhD 
Senior Clinical & Regulatory Consultant 
Date 
3


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 3 of 28 
 
VERSION CONTROL 
Version 
Date 
Author 
Description of Changes 
1.0 
2023/02/22 
Riddhi Thakkar 
Not applicable 
1.1 
2023/04/26 
Riddhi Thakkar 
To provide the safety data analysis by 
combined active and pooled placebo 
groups. 
 
 
4


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 4 of 28 
 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN APPROVAL ..........................................................................2 
VERSION CONTROL ....................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
TABLE OF TABLES ......................................................................................................................6 
ABBREVIATIONS .........................................................................................................................7 
1 
INTRODUCTION ..................................................................................................................8 
2 
STUDY OBJECTIVES ..........................................................................................................9 
3 
STUDY DESIGN .................................................................................................................10 
3.1 
General Description .........................................................................................................10 
3.2 
Treatments .......................................................................................................................11 
3.3 
Study Procedures .............................................................................................................11 
3.4 
Randomization and Blinding Procedures ........................................................................11 
3.5 
Sample size ......................................................................................................................12 
4 
ANALYSIS POPULATIONS ..............................................................................................13 
5 
STUDY SUBJECTS ............................................................................................................14 
5.1 
Disposition .......................................................................................................................14 
5.2 
Protocol Deviations .........................................................................................................14 
6 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ...............................15 
7 
PHARMACOKINETIC ANALYSES .................................................................................16 
7.1 
Pharmacokinetic Statistical Methodology .......................................................................16 
7.2 
Summary Statistics ..........................................................................................................16 
7.3 
Statistical Analysis ..........................................................................................................16 
8 
SAFETY ANALYSIS ..........................................................................................................17 
8.1 
Adverse Events ................................................................................................................17 
8.2 
Adverse Events of Special Interest (AESI) .....................................................................18 
8.3 
Clinical Laboratory Evaluations ......................................................................................18 
8.4 
Vital Signs .......................................................................................................................20 
8.5 
Physical Examination Findings .......................................................................................20 
8.6 
12-lead Electrocardiogram ..............................................................................................20 
5


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 5 of 28 
 
9 
DATA HANDLING AND PRESENTATION ....................................................................21 
9.1 
Safety Analysis Presentation ...........................................................................................21 
9.2 
Baseline ...........................................................................................................................22 
10 
INTERIM ANALYSES AND DATA SAFETY MONITORING .......................................23 
11 
GENERAL INFORMATION RELATED TO DATA PRESENTATIONS ........................24 
APPENDIX A 
STUDY SCHEDULE(S) ..............................................................................25 
6


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 6 of 28 
 
TABLE OF TABLES 
Table 1: 
Objectives and Related Endpoints ............................................................................. 9 
Table 2: 
Ascending Doses of AL001 for Each Cohort .......................................................... 11 
Table 3: 
Data Presentations for Study Subject Information................................................... 14 
Table 4: 
Data Presentations for Demographic and Other Baseline Characteristics ............... 15 
Table 5: 
Data Presentations for Safety Assessments ............................................................. 17 
Table 6: 
Clinical Laboratory Evaluations .............................................................................. 18 
 
7


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 7 of 28 
 
ABBREVIATIONS 
AD 
Alzheimer’s disease 
AE 
Adverse event 
CI 
Confidence interval 
COVID-19 
Coronavirus sars-cov2 
CRO 
Clinical research organization 
CV 
Coefficient of variation 
DMP 
Data management plan 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
ET 
Early termination 
FDA 
Food and drug administration 
ICF 
Informed consent form 
ICH 
International council for harmonisation 
IEC 
Independent ethics committee 
IMP 
Investigational medicinal product 
IP 
Investigational product 
MAD 
Multiple ascending dose 
MMSE 
Mini-Mental State Examination 
MTD 
Maximum tolerated dose 
PK 
Pharmacokinetic 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOC 
System organ class 
SOP 
Standard operating system 
TEAE 
Treatment-emergent adverse event 
TID 
3 times daily 
WHO-DD 
World Health Organization drug dictionary 
 
 
8


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 8 of 28 
 
1 
INTRODUCTION 
This statistical analysis plan (SAP) provides a detailed description of the statistical methods and 
procedures to be implemented for the analyses of data from protocol AL001-ALZ02.The analyses 
described in the SAP are based upon the final protocol version 8.0 (Amendment 06) dated 
2022/11/28. 
 
 
9


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 9 of 28 
2 
STUDY OBJECTIVES 
The objectives of the study and corresponding study endpoints are detailed in Table 1. 
Table 1: Objectives and Related Endpoints
Objective 
Endpoint 
Analysis 
Primary 
To evaluate the safety and 
tolerability of AL001 under 
multiple-dose, steady-state 
conditions in Alzheimer’s 
subjects and healthy adult 
subjects. 
Vital signs (blood pressure, heart rate, and oral
body temperature)
12-lead electrocardiogram
Physical examination
Safety laboratory tests (hematology, chemistry
[including thyroid-stimulating hormone (TSH),
vitamin B12, and Mg], HbA1c, and urinalysis
Reported and observed Adverse events
(AEs)/serious AEs)/tolerability observations
including signs and/or symptoms of lithium and/or
salicylate toxicity
Refer to 
Section 8 
Secondary 
To characterize the Maximum 
tolerated dose (MTD) of AL001 
in patients with mild to 
moderate Alzheimer’s disease 
(AD) and healthy adult subjects. 
Prevalence of peak salicylate 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 Alzheimer’s subjects.
Refer to 
Section 7 
Exploratory 
To explore the difference in PK 
profile between the non-elderly 
vs elderly subjects (healthy 
subjects only).  
Descriptive statistics for PK will be presented by
treatment group and compared between non-
elderly and elderly subjects.
Refer to 
Section 7 
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:  
• facilitate recruitment into
subsequent AL001 clinical trials
• facilitate trial-adherence to
completion of study
requirements including
treatment adherence
Demographic characteristics of all screened and
successfully enrolled AD subjects will be
documented to determine what AD subject
characteristics are needed and appropriate for
successful recruitment and adherence to treatment
and study requirements in future Phase 2 and 3
clinical studies. Baseline Mini-Mental State
Examination scores, FDA classifications (protocol
APPENDIX 3) and demographic characteristics,
for example, will be reviewed for relationship to
AD subjects’ ability to provide informed consent
and complete study requirements.
Refer to 
Section 6 
10


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 10 of 28 
 
3 
STUDY DESIGN  
3.1 
General Description 
This is a Phase 1/2a, multi-center, double-blind, placebo-controlled, randomized, MAD clinical 
study to determine the safety and MTD of AL001 in subjects with mild to moderate AD (FDA 
Classification of Stage 2 to 4 AD [protocol APPENDIX 3]) and healthy adult subjects. Cohorts 1, 
2b, 3b, 4b, and 5b will include AD subjects (between the ages of 50 and 80 years, inclusive) and 
Cohorts 2a, 3a, 4a, and 5a will 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). In 
each of the 9 cohorts, subjects will be confined to the study site from Day -1 until Day 15.  
The study consists of 3 phases. 
1. Screening Phase – up to 28 days (from Days -28 to -1)  
2. Treatment Phase – 16 days:  
o Subjects will be admitted to the study site on Day -1. Subjects will receive 14 days 
of 3 times daily (TID) dosing with assigned study medication from Days 1 to 14 
and will remain confined until Day 15.  
o Each of the 9 cohorts will be initiated sequentially starting with Cohort 1 and 
progressing through to Cohort 5 depending on acceptable review of the safety data 
by a 3-member expert adjudication panel. Each of the Cohorts 2 to 5 will be sub-
divided into 2 cohorts: Cohorts 2a, 3a, 4a, and 5a will include healthy subjects and 
Cohorts 2b, 3b, 4b, and 5b will include AD subjects. The results from the healthy 
subject cohorts ‘a’ will be reviewed by the independent safety adjudication 
committee and if assessed as safe, the committee will permit progression to the 
corresponding 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 can 
proceed to the next higher dose level without having to wait for the corresponding 
AD subject cohort to be completed and reviewed by the safety adjudication panel. 
o The initiation of the next dose cohort may be delayed up to approximately 4 weeks 
following the last dose of the last subject in the preceding cohort. This is necessary 
to allow time for the safety and PK data to be compiled and tabulated for review by 
the safety committee (laboratory reports, AEs, tolerability, and PK data from all [up 
to 8] completed subjects in each cohort), to determine if it is safe to proceed with 
enrollment of the subsequent cohort. 
3. Follow-up Phase - 1 month  
o Subjects will be 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 patient will participate in the study for up to approximately 2.5 months. 
11


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 11 of 28 
3.2 
Treatments 
Cohort 1 will include 8 AD subjects (6 active and 2 placebo). Each of the Cohorts 2 to 5 will be 
sub-divided into 2 cohorts: Cohorts 2a, 3a, 4a, and 5a will include healthy subjects and Cohorts 2b, 
3b, 4b, and 5b will include AD subjects. For each cohort, subjects will be randomized to 1 of 2 
treatment groups in a 6:2 ratio of AL001 (active study medication) to placebo. Subjects in each of 
the cohorts will be dosed TID for 14 days at the dose level indicated in Table 2 below or placebo 
Active Group: Ascending doses of AL001 are manufactured in 210 mg 0 size capsules; the number 
of capsules for each cohort dosing will vary based on the AL001 dosing equivalent (refer to Table 
2 ). Dosing will be TID at approximately 8:00 AM, 2:00 PM, and 8:00 PM (within ±10 minutes). 
Patients will be fasted for each dose (dosed at least 1 hour before or 4 hours after meals).  
Placebo Group: The placebo capsules will be manufactured to appear exactly as the capsule used 
for AL001; the number of capsules dosed, number of doses, dosing schedule, and fasting 
conditions will be the same as for the active group. 
Table 2: Ascending Doses of AL001 for Each Cohort 
Cohort 
Daily Dosing Level 
No. of AL001 
210 mg Capsules 
AL001 Daily Dose 
Equivalent 
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. 
a.
Lithium dose equivalent to that used for bipolar/affective disorders.
3.3 
Study Procedures 
For complete details on the study assessments to be performed, refer to APPENDIX A. 
3.4 
Randomization and Blinding Procedures 
Subjects will be randomized by computer in a ratio of 6:2 (active:placebo) in each of the 9 cohorts. 
The randomization will be performed separately for AD subject cohorts and healthy subject 
cohorts. For the AD subject cohorts (Cohorts 1, 2b, 3b, 4b, and 5b) subjects will be randomized in 
a 6:2 ratio (active:placebo) and for the healthy subject cohorts (Cohorts 2a, 3a, 4a, and 5a), the 
randomization will be performed in such a way that age will be used as a stratification factor for 
each cohort: 3 non-elderly and 3 elderly subjects will receive AL001, and 1 non-elderly and 1 
elderly subject will receive placebo.  
12


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 12 of 28 
 
The subjects will be assigned a Screening Number (upon signing the informed consent at the 
Screening Visit) and a Subject Randomization Number (upon meeting eligibility criteria on Day 1) 
sequentially by the Investigator or authorized study staff. The Subject Randomization Numbers 
will start with 1001 for Cohort 1, 2001 for Cohort 2, etc. Prior to dosing on Day 1, the subject is 
assigned the next sequential randomization number for that cohort. Once a Subject Randomization 
Number is assigned to a subject, it will not be reused. The subject ID number will be the 
combination of the Screening Number and the Randomization Number.  
A key to the randomization will be kept secured by the Sponsor’s Medical Monitor or other 
Sponsor representative not involved in this study, in a sealed envelope under secure conditions at 
the study site for emergency use. In the occurrence of an SAE, or other safety issue which requires 
knowing the patient’s treatment group, the Medical Monitor will unblind that patient.  
3.5 
Sample size 
A maximum of 5 cohorts of 8 AD subjects each and 4 cohorts of 8 healthy subjects each will be 
enrolled in this clinical trial for a maximum total of 72 subjects. Each cohort will correspond to 
one of the 5 given dose level of AL001 and will be comprised of 6 subjects receiving AL001 and 2 
subjects receiving placebo. This sample size is not based on any statistical considerations, but is 
judged adequate to meet the primary objective of this clinical trial. 
 
 
13


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 13 of 28 
 
4 
ANALYSIS POPULATIONS 
The following analysis sets will be defined: 
 Screened Analysis Set: The Screened Analysis Set will include all the subjects who have 
signed the inform consent form.  
 Randomized Analysis Set: The Randomized Analysis Set will include all subjects who are 
randomized within one of the cohorts. 
 Safety Analysis Set: The Safety Analysis Set will include all subjects in the Randomized 
Analysis Set who receive any dose of study drug. This analysis set will be utilized for all 
safety analyses. 
 Pharmacokinetic Analysis Set: The PK Analysis Set will include all subjects in the Safety 
Analysis Set who receive AL001 and have either a Cmax measurement for salicylate or a 
trough measurement for lithium. This analysis set will be utilized for all PK analyses. 
 
 
14


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 14 of 28 
5 
STUDY SUBJECTS 
Disposition data, analysis population information, and protocol deviations will be listed 
and summarized as described in Table 3.   
Table 3: Data Presentations for Study Subject Information 
Data 
Variables 
Presentation 
Disposition and analysis 
population 
Subject, completion status (i.e., 
completed or withdrawn), reason for 
withdrawal, analysis set determination 
Listings: 
Randomization
Disposition
Analysis set
Table: 
Disposition
Protocol deviations 
Protocol deviations 
Listings: 

Protocol deviations
5.1 
Disposition 
Subject disposition will be summarized for all subjects randomized. The following will be 
presented: 

Number of subjects (N) screened

N of subjects randomized

N and % of subjects who completed the study

N and % of subjects who withdrew from the study by primary reason for withdrawal

N and % of subjects included in each analysis set
The percentages will be calculated using the number of randomized subjects as the denominator. 
The summary will be presented by treatment (dose level of AL001, pooled placebo and overall) 
for AD cohorts and Healthy cohorts.  
5.2 
Protocol Deviations 
Deviations identified at the site will be collected in the clinic deviation tracking system (DTS) and 
presented in a protocol deviation listing. Protocol deviations will be reviewed by the Sponsor, 
principal investigator, and lead statistician and finalized before unblinding the study. Protocol 
deviations will be listed for the safety population. 
15


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 15 of 28 
6 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Unless otherwise specified, all available data will be listed, summarized, for demographics and 
other baseline characteristics, and presented for all study population as detailed in Table 4. 
The screened analysis set will be used for exploratory analysis. 
Table 4: Data Presentations for Demographic and Other Baseline Characteristics 
Data 
Variables 
Presentation 
Demographic and Other 
Baseline Characteristics 
Sex, age, ethnicity, race, height, 
weight and body mass index (BMI), 
Mini-Mental State Examination 
(MMSE) scores, and AD stage FDA 
classification for AD subjects only 
Listing 
Table – presented for all study 
populations (Screened, 
Randomized, Safety and PK). 
Medical history 
All medical history findings 
Listing 
Prior and Concomitant 
medications 
All medications taken prior to 
study drug administration 
and concomitant medications 
Listing 
16


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 16 of 28 
 
7 
PHARMACOKINETIC ANALYSES 
7.1 
Pharmacokinetic Statistical Methodology 
All PK tables, figures and listings (TFLs), when appropriate, will be stratified by treatment and 
cohort for each study part.  
7.2 
Summary Statistics 
In order to characterize the MTD of AL001 in subjects with AD and healthy subjects, descriptive 
statistics will be presented by treatment group for each cohort and overall for the following: 
o Proportion of healthy non-elderly subjects with trough lithium concentrations > 1.2 mEq/L 
o Proportion of subjects with peak (Cmax) salicylate concentrations > 30 mg/dL 
o Proportion of healthy elderly and, separately, Alzheimer’s subjects with plasma trough 
measurements of lithium  > 1.0 mEq/L 
Summary statistics of the plasma concentration data will be calculated for the PK population, 
unless otherwise indicated. Summary statistics will be calculated for concentration at each 
individual time point.  
Concentration data will be 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), standard deviation (SD), geometric mean, minimum (min), median, 
maximum (max), and coefficient of variation (CV%).  
7.3 
Statistical Analysis 
In order to assess whether PK steady state has been approximately achieved, descriptive statistics 
for trough (Cmin) measurements of plasma lithium and Cmax (peak) measurements of plasma 
salicylate will be presented for all available days  by cohort and overall. In addition, these 
measurements for plasma lithium and salicylate on Days 13 and 14 for each cohort will be loge-
transformed and a 90% CI for the difference in the measurements between Days 13 and 14 for 
lithium and salicylate will be calculated on the loge scale and then transformed back to the original 
scale for each cohort. If the 90% CI on the original scale is contained within the interval 85.0% to 
117.6%, then an approximation of steady state will be concluded for the respective analyte and 
cohort. Alternative approaches to estimate achievement of steady-state conditions are to be used, 
as appropriate, such as when at least 3 trough concentrations for plasma lithium and/or at least 3 
Cmax concentrations for plasma salicylate can be assessed using linear regression. All cohorts 
except Cohort 1 are expected to complete at least 3 lithium trough and 3 salicylate peak 
concentration  measurements and should be candidates for this statistical approach. 
 
17


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05
Page 17 of 28 
8 
SAFETY ANALYSIS 
Unless otherwise specified, all available data will be listed and summary tables for safety 
assessments will be presented by treatment (dose level of AL001 and pooled placebo) per cohort 
for the safety population as detailed in Table 5 and all applicable safety data will be presented by 
combined active and pooled placebo groups, such as, disposition, demographic, adverse events, 
labs, vital signs, and 12-ECG data. 
Continuous variables will be summarized (absolute values and change from baseline) using 
descriptive statistics (n, mean, SD, minimum, median and maximum).  
Table 5: Data Presentations for Safety Assessments 
Data 
Variables 
Presentation 
Adverse events 
Adverse event (AE) 
description, date and time (start 
and end), 
intensity, relationship to study 
drug, action taken, study days 
and outcome 
Listing 
Table 
Extent of 
exposure 
Study drug administration dose, 
units, date, time, cohort 
Listing 
Clinical 
laboratory 
evaluations 
Laboratory results (refer to section 
8.3 for parameters) 
Listing 
Table 
Vital signs 
Blood pressure, pulse, and body 
temperature 
Listing 
Table 
Physical 
examinations 
Physical examinations findings 
Listing 
12-Lead ECGs 
ECG interpretations and findings 
Listing 
Table 
8.1 
Adverse Events 
Treatment-emergent adverse events (TEAEs) are AEs that are not present prior to the exposure to 
study treatment. All AEs reported following exposure to study treatment are considered TEAEs.  
All TEAEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 25.0. The listing and summaries will include coded System Organ Class (SOC) and 
Preferred Term (PT). 
An overall summary by treatment (dose level of AL001 and pooled placebo and overall) will 
present the number and percentage of subjects with: 

At least one TEAE

At least one drug-related TEAE

Severity intensity
18


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 18 of 28 
o Mild
o Moderate
o Severe
o
Life-threatening
o
Death

at least one SAE

at least one drug-related SAE

death
For the study, the following AE tables will also be presented: 

TEAEs by SOC and PT

SAEs by SOC and PT

Drug-related TEAEs by SOC and PT

TEAEs by SOC, PT, and maximum intensity

TEAEs that lead to premature discontinuation
Events will be listed by treatment, subject and AE onset date. Treatment-emergent AE duration 
(stop date/time - start date/time) will be included in the listing. 
8.2 
Adverse Events of Special Interest (AESI) 
Adverse events of special interest (AESI) for this study is upper gastrointestinal upset (lower 
gastrointestinal; diarrhea). The number and percentage of subjects with an AESI, as well as the 
total number of AESIs, will be summarized for each cohort and overall by SOC and PT. 
8.3 
Clinical Laboratory Evaluations 
Laboratory data will be presented using units as reported by the clinical laboratory. Specific 
hematology, chemistry, and urinalysis parameters are listed in Table 6. 
Table 6: Clinical Laboratory Evaluations 
Hematology 
Serum chemistry 
Complete blood count including: 
Red blood cells (RBCs), hemoglobin, hematocrit, 
reticulocytes, mean corpuscular volume, mean 
corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, platelet count 
White blood cell (WBC) count with differential 
including (absolute and percentage): 
neutrophils, lymphocytes, monocytes, eosinophils, 
basophils, band neutrophils 
HbA1ca 
Albumin 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Alkaline phosphatase (ALP) 
Blood Urea Nitrogen (BUN) or Urea 
Bicarbonate 
Creatinine 
Electrolytes (Na, K, Cl, Ca, P) 
Glucose (fasting) 
Lactate dehydrogenase (LDH) 
Total bilirubin 
Direct bilirubin 
Total cholesterol,  
High-density lipoprotein (HDL)c 
Low-density lipoprotein (LDL)c 
Triglyceridesc 
TSHa 
Mg 
19


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 19 of 28 
 
Vitamin B12a 
Urinalysis 
Urobilinogen  
Glucose  
Ketones  
Bilirubin  
Protein  
Nitrate 
Leukocytes 
Blood 
pH 
Specific gravity 
Abbreviations: TSH = thyroid-stimulating hormone. 
a. Performed at Screening and Day 23 or early termination only. 
b. Urobilinogen may be measured via a urine dipstick test at the site if their local laboratory does not include it in 
their urinalysis panel. 
c. 
Lipid panel (total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides) measured at 
the Screening Visit does not need to be repeated on Day -1. 
Absolute values for continuous parameters (hematology, general biochemistry, and urinalysis) will 
be summarized using descriptive statistics by each cohort (dose level of AL001 and pooled 
placebo; overall) and change from baseline will be presented.  
Number (Percentage) of Subjects with Normal, Abnormal Clinically Significant (CS) and 
Abnormal Non-Clinically Significant (NCS) values will be presented for each laboratory category 
by each cohort (dose level of AL001 and pooled placebo, overall) and visit. 
Serology, alcohol/drug screen, pregnancy test results will be presented in separate listings. 
Data listings will include out-of-range flags (Low, High) and whether the abnormal values are 
clinically significant or not. 
20


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 20 of 28 
 
8.4 
Vital Signs 
Vital signs will include heart rate, blood pressure, and body temperature. 
Absolute values in vital signs measurements will be summarized descriptively by each cohort 
(dose level of AL001 and pooled placebo; overall), time point and change from baseline will be 
presented.  
Number (%) of subjects with Normal, Abnormal Clinically Significant (CS) and Abnormal Non-
Clinically Significant (NCS) values of vital signs will be presented by each cohort (dose level of 
AL001 and pooled placebo, overall), visit and time point. 
Data listing will identify if values are “abnormal, clinically significant” or “abnormal, not 
clinically significant”. Vital sign results will be presented. 
8.5 
Physical Examination Findings 
The physical examination will include a general review of the following body systems (at 
minimum): general appearance, head and neck, cardiovascular, respiratory, abdomen, and brief 
neurological examination. 
Physical examination results will be listed as normal or abnormal. Abnormal findings of clinical 
significance will be included in the listing.  
8.6 
12-lead Electrocardiogram  
12- Lead safety ECG results will be summarized descriptively by each cohort ((dose level of 
AL001 and pooled placebo, overall), time point and change from baseline will be presented. 
Number (%) of subjects with Normal, Abnormal Clinically Significant (CS) and Abnormal Non-
Clinically Significant (NCS) values of ECG will be presented by each cohort (dose level of AL001 
and pooled placebo, overall), visit and time point. 
Data listing will identify if values are “abnormal, clinically significant” or “abnormal, not 
clinically significant”.  
 
 
21


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 21 of 28 
 
9 
DATA HANDLING AND PRESENTATION 
All safety and statistical outputs will be generated using SAS software, version 9.4. 
All programs used to generate statistical analyses will be validated according to Altasciences’s 
standard operating procedure (SOPs). 
Tables, figures and listings will be provided in RTF formats. 
9.1 
Safety Analysis Presentation 
Adverse events and medical history will be classified using the MedDRA terminology as defined 
in the study data management plan (DMP).  
Prior and concomitant medications will be coded with the World Health Organization drug 
dictionary (WHO-DD) (March 2022 B3) as defined in the study DMP. 
 
Generally, summaries will be presented by cohort (dose level of AL001 and pooled placebo, 
overall). Some summaries will also be presented to include overall (i.e., subject disposition and 
demographics) Also, applicable safety data will be presented by combined active and pooled 
placebo groups, such as, disposition, demographic, adverse events, labs, vital signs, and 12-ECG 
data. 
Summaries for data collected at scheduled times specified in the protocol will be presented by 
cohort (dose level of AL001 and pooled placebo, overall), visit, and, where applicable, time point. 
Continuous variables will be summarized using the number of observations, mean, standard deviation, 
minimum, median, and maximum. Categorical variables will be summarized using the number of 
observations and the corresponding percentage. 
In general, the data listings will include data from all subjects who receive at least one dose of 
either AL001 or placebo.  
Study days will be included in adverse event and concomitant medication listings in addition to 
dates. Study days will be calculated relative to the first day of double-blind treatment (Day 1) 
derived as (event date - first day of AL001 or placebo dosing) +1 for events after the first day of 
dosing and (event date - first day of AL001 or placebo dosing) for events before the first day of 
dosing. 
The following general comments also apply to all statistical analyses and data presentations: 
 Duration variables will be calculated using the general formula: (end date - start date) +1. 
 If the reported value of a clinical laboratory parameter cannot be used in a statistical 
summary table (e.g., a character string is reported for a parameter of the numerical type), a 
coded value must be appropriately determined and used in the statistical analyses.  In 
general, a value or lower and upper limit of normal range such as ‘<10’ or ‘≤5’ will be 
treated as ‘10’ or ‘5’ respectively, and a value such as ‘>100’ will be treated as ’100’.  
However, the actual values as reported in the database will be presented in data listings. 
 When assessments are repeated for a given time point or performed at unscheduled times, 
only the result which is the closest to the dosing time will be included in summary tables. 
22


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 22 of 28 
 
In general, summary statistics for raw variables (i.e., variables measured at the study site or central 
laboratory) will be displayed as follows:  
 Minima and maxima will be displayed to the same number of decimal places as the raw 
data.  
 Means, medians, and quartiles will be displayed to 1 additional decimal place.  
 Standard deviations will be displayed to 2 additional decimal places.   
 Percentages will be displayed to 1 decimal place. Percentages between 0 and 0.1 
(exclusive) will be displayed as ‘<0.1’.   
 P-values will be displayed to 3 decimal places. P-values that are less than 0.001 will be 
displayed as ‘<0.001’ if applicable. 
The number of decimal places for summary statistics of derived variables (i.e., variables that are 
not measured by the study site but are calculated for analysis based on other measured variables) 
will be determined on a case by case basis.  In general:  
 Minima and maxima will be displayed to the commonly used unit of precision for the 
parameter.  
 Means, medians, quartiles, and confidence limits will be displayed to 1 additional decimal 
place.  
 Standard deviations will be displayed to 2 additional decimal places.  
9.2 
Baseline 
The baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) 
collected before the first dose of study drug in each cohort. 
 
23


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 23 of 28 
 
10 INTERIM ANALYSES AND DATA SAFETY MONITORING 
There is no interim analysis plan for this study.  
 
24


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 24 of 28 
 
11 GENERAL INFORMATION RELATED TO DATA PRESENTATIONS 
The formats and layouts of TFLs are provided in a separate document and are common displays.  
Their numbering and general content follow the International Conference on Harmonisation (ICH) 
E3 guidelines.  Actual formats and layouts may be altered slightly from those presented as 
necessary to accommodate actual data or statistics.  
Minor format changes will not require updates to the SAP; rather they may be documented in a 
Note to SAP. 
25


Protocol Number: AL001-ALZ02 
Alzamend Neuro, Inc. 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
 
APPENDIX A STUDY SCHEDULE(S) 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Informed Consent 
X 
Admission1 
X 
Clinic Confinement 
X 
X 
Discharge 
X 
Medical and Surgical History 
X 
Physical Examination 
X 
X 
X 
X 
Demographic information 
X 
Body Height/Body Weight 
X 
Vital Signs2 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG3 
X 
X 
X 
X 
X 
X 
 
 
 
 
1 Subjects will be admitted to the clinical research unit at least 16 hours prior to the first study drug administration. 
2 Vital signs will include blood pressure, heart rate and oral body temperature. On Days 1 to 14, vital signs will be measured 
within 1 hour prior to dosing using the same arm, if possible, after 5 minutes in seated position. 
26


Protocol Number: AL001-ALZ02 
Alzamend Neuro, Inc. 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
 
 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Safety Laboratory Tests4 
X 
X 
X 
X 
X 
X 
Serology (HIV/HBV/HCV) 
X 
Serum Pregnancy Test (females 
of childbearing potential only) 
X 
Urine Pregnancy Test (females 
of childbearing potential only) 
X 
COVID-19 Test5 
X 
X 
Urine Drug Screen and Alcohol 
Breath or Urine Test 
X 
X 
Inclusion/Exclusion Criteria 
X 
X 
Randomization 
X 
Fasted Study Drug 
X 
X 
 
 
3 On Day 1, ECGs will be conducted pre-dose and 1 hour (±10 minutes) after the third dose of Day 1. On Days 7, 13, and 14, ECGs will be performed prior to 
first daily dose. 
4 Safety laboratory tests (chemistry, hematology, and urinalysis) will be performed on Day -1, Day 7 (pre-dose), Day 15, and Day 23. For all subjects, 
total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides will not be included in the safety laboratory tests performed on Day 
-1. For subjects who are screened within 5 days of check-in (on Day -6 to Day -2), the safety laboratory tests will not be performed on Day -1. 
5 The COVID-19 test should be repeated upon check-in on Day -1 using a COVID rapid antigen test kit or PCR. Additionally,, study site and local health 
authority policies and recommendations can be applied for compliance. If the initial result is positive at the Screening Visit, the test may be repeated after 14 
days or on Day -1 whichever comes first. 
27


Protocol Number: AL001-ALZ02 
Alzamend Neuro, Inc. 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
 
 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Administration (all doses) 
Baseline and Trough plasma 
lithium and peak plasma 
salicylate concentration 
measurements6 
X 
X 
X 
MMSE Score (AD subjects 
only) 
X 
Hachinski Ischemic Scale 
Score7 (AD subjects only) 
X 
Meals8 
X 
X 
X 
X 
 
 
 
6 Blood samples for baseline plasma lithium and plasma salicylate concentration measurements will be collected before first dose on Day 1. Blood samples for 
trough plasma lithium and peak plasma salicylate concentration measurements will be collected on Days 3, 5, 7, 10, 13, and 14, and at the discretion of the 
Investigator (the latter are ‘Safety Samples’ for Therapeutic Drug Monitoring), particularly to assess the relationship to possible lithium or salicylate related 
AEs. These safety samples could be sent for expedited analysis to either a local laboratory with an aliquot saved for the bioanalytical laboratory, or to the 
bioanalytical laboratory directly (Sannova or Altasciences). In addition, for AD subject Cohorts 2b, 3b, 4b, and 5b, the trough lithium sample on Day 5 will be 
treated as a ‘Safety Sample’ for Therapeutic Drug Monitoring to assess any lithium-related PK exposure safety concerns at an early treatment time point which 
may require dosing to be discontinued for an individual subject. This sample will be sent to Sannova for expedited analysis. Similarity between Days 13 and 14 
trough lithium plasma levels and peak salicylate plasma levels will be used to determine the status of lithium and salicylate steady-state PK conditions, and/or 
by another appropriate method, such as linear regression. Blood collection for trough lithium plasma concentrations will occur just prior to the first daily dose, 
while blood collection for peak plasma salicylate concentrations will occur at 1.25 hours post third daily dose (the estimated time to a maximum blood 
concentration Cmax). For early termination, blood samples for lithium and salicylate plasma concentrations will be collected. A ±10-minute window will be 
allowed for collection of PK samples for both lithium and salicylate. 
7 Hachinski Ischemic Scale Score is presented in protocol APPENDIX 5. 
28


 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.1 | 2023/05/05 
Page 28 of 28 
 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Adverse Event 
Reporting/Safety-Tolerability 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
Prior Medications 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Health Status Questionnaire 
(SF-36) 
X 
X 
X 
Abbreviations: AD = Alzheimer’s disease; COVID-19 = Coronavirus Disease 2019; ECG = electrocardiogram; ET = Early Termination; HBV = hepatitis B 
virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; MMSE = Mini-Mental State Exam; PK = pharmacokinetic(s); TSH = thyroid-stimulating 
hormone 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 Meals during confinement should include breakfast (at least 1 hour after first dose), lunch (at least 1 hour after second dose), dinner (at least 1 hour after 
third  dose), and a snack (if time permits and 10-hour fast is respected). On Day 15, breakfast will be provided prior to subject/caregiver being 
discharged from the study site. 
 
29


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
For: 
Alzamend Neuro, Inc. 
PROTOCOL No. AL001-ALZ02 
 
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”) 
Altasciences Project No. ALZ-P9-319 
Prepared by: 
Altasciences Company Inc. 
575 Armand-Frappier Boulevard 
Laval, Quebec 
Canada, H7V 4B3 
 
Version: Final 1.0 
Date: 2023-02-22 
 
30


 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 2 of 28
 
 
We have carefully read this statistical analysis plan and agree it contains the necessary information 
required to handle the statistical analysis of study data. 
 
 
 
 
 
Riddhi Thakkar 
Biostatistician II, Altasciences 
 
Date  
 
On behalf of the Sponsor: 
 
 
 
 
 
Eve del Rio, MD, PhD 
Senior Clinical & Regulatory Consultant 
 
Date  
 
 
31


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 3 of 28 
 
VERSION CONTROL 
Version 
Date 
Author 
Description of Changes 
1.0 
2023/02/22 
Riddhi Thakkar 
Not applicable 
 
 
32


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 4 of 28 
 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN APPROVAL ..........................................................................2 
VERSION CONTROL ....................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
TABLE OF TABLES ......................................................................................................................6 
ABBREVIATIONS .........................................................................................................................7 
1 
INTRODUCTION ..................................................................................................................8 
2 
STUDY OBJECTIVES ..........................................................................................................9 
3 
STUDY DESIGN .................................................................................................................10 
3.1 
General Description .........................................................................................................10 
3.2 
Treatments .......................................................................................................................11 
3.3 
Study Procedures .............................................................................................................11 
3.4 
Randomization and Blinding Procedures ........................................................................11 
3.5 
Sample size ......................................................................................................................12 
4 
ANALYSIS POPULATIONS ..............................................................................................13 
5 
STUDY SUBJECTS ............................................................................................................14 
5.1 
Disposition .......................................................................................................................14 
5.2 
Protocol Deviations .........................................................................................................14 
6 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ...............................15 
7 
PHARMACOKINETIC ANALYSES .................................................................................16 
7.1 
Pharmacokinetic Statistical Methodology .......................................................................16 
7.2 
Summary Statistics ..........................................................................................................16 
7.3 
Statistical Analysis ..........................................................................................................16 
8 
SAFETY ANALYSIS ..........................................................................................................17 
8.1 
Adverse Events ................................................................................................................17 
8.2 
Adverse Events of Special Interest (AESI) .....................................................................18 
8.3 
Clinical Laboratory Evaluations ......................................................................................18 
8.4 
Vital Signs .......................................................................................................................19 
8.5 
Physical Examination Findings .......................................................................................19 
8.6 
12-lead Electrocardiogram ..............................................................................................20 
33


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 5 of 28 
 
9 
DATA HANDLING AND PRESENTATION ....................................................................21 
9.1 
Safety Analysis Presentation ...........................................................................................21 
9.2 
Baseline ...........................................................................................................................22 
10 
INTERIM ANALYSES AND DATA SAFETY MONITORING .......................................23 
11 
GENERAL INFORMATION RELATED TO DATA PRESENTATIONS ........................24 
APPENDIX A 
STUDY SCHEDULE(S) ..............................................................................25 
34


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 6 of 28 
 
TABLE OF TABLES 
Table 1: 
Objectives and Related Endpoints ............................................................................. 9 
Table 2: 
Ascending Doses of AL001 for Each Cohort .......................................................... 11 
Table 3: 
Data Presentations for Study Subject Information................................................... 14 
Table 4: 
Data Presentations for Demographic and Other Baseline Characteristics ............... 15 
Table 5: 
Data Presentations for Safety Assessments ............................................................. 17 
Table 6: 
Clinical Laboratory Evaluations .............................................................................. 18 
 
35


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 7 of 28 
 
ABBREVIATIONS 
AD 
Alzheimer’s disease 
AE 
Adverse event 
CI 
Confidence interval 
COVID-19 
Coronavirus sars-cov2 
CRO 
Clinical research organization 
CV 
Coefficient of variation 
DMP 
Data management plan 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
ET 
Early termination 
FDA 
Food and drug administration 
ICF 
Informed consent form 
ICH 
International council for harmonisation 
IEC 
Independent ethics committee 
IMP 
Investigational medicinal product 
IP 
Investigational product 
MAD 
Multiple ascending dose 
MMSE 
Mini-Mental State Examination 
MTD 
Maximum tolerated dose 
PK 
Pharmacokinetic 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOC 
System organ class 
SOP 
Standard operating system 
TEAE 
Treatment-emergent adverse event 
TID 
3 times daily 
WHO-DD 
World Health Organization drug dictionary 
 
 
36


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 8 of 28 
 
1 
INTRODUCTION 
This statistical analysis plan (SAP) provides a detailed description of the statistical methods and 
procedures to be implemented for the analyses of data from protocol AL001-ALZ02.The analyses 
described in the SAP are based upon the final protocol version 8.0 (Amendment 06) dated 
2022/11/28. 
 
 
37


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 9 of 28 
2 
STUDY OBJECTIVES 
The objectives of the study and corresponding study endpoints are detailed in Table 1. 
Table 1: Objectives and Related Endpoints
Objective 
Endpoint 
Analysis 
Primary 
To evaluate the safety and 
tolerability of AL001 under 
multiple-dose, steady-state 
conditions in Alzheimer’s 
subjects and healthy adult 
subjects. 
Vital signs (blood pressure, heart rate, and oral
body temperature)
12-lead electrocardiogram
Physical examination
Safety laboratory tests (hematology, chemistry
[including thyroid-stimulating hormone (TSH),
vitamin B12, and Mg], HbA1c, and urinalysis
Reported and observed Adverse events
(AEs)/serious AEs)/tolerability observations
including signs and/or symptoms of lithium and/or
salicylate toxicity
Refer to 
Section 8 
Secondary 
To characterize the Maximum 
tolerated dose (MTD) of AL001 
in patients with mild to 
moderate Alzheimer’s disease 
(AD) and healthy adult subjects. 
Prevalence of peak salicylate 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 Alzheimer’s subjects.
Refer to 
Section 7 
Exploratory 
To explore the difference in PK 
profile between the non-elderly 
vs elderly subjects (healthy 
subjects only).  
Descriptive statistics for PK will be presented by
treatment group and compared between non-
elderly and elderly subjects.
Refer to 
Section 7 
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:  
• facilitate recruitment into
subsequent AL001 clinical trials
• facilitate trial-adherence to
completion of study
requirements including
treatment adherence
Demographic characteristics of all screened and
successfully enrolled AD subjects will be
documented to determine what AD subject
characteristics are needed and appropriate for
successful recruitment and adherence to treatment
and study requirements in future Phase 2 and 3
clinical studies. Baseline Mini-Mental State
Examination scores, FDA classifications (protocol
APPENDIX 3) and demographic characteristics,
for example, will be reviewed for relationship to
AD subjects’ ability to provide informed consent
and complete study requirements.
Refer to 
Section 6 
38


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 10 of 28 
 
3 
STUDY DESIGN  
3.1 
General Description 
This is a Phase 1/2a, multi-center, double-blind, placebo-controlled, randomized, MAD clinical 
study to determine the safety and MTD of AL001 in subjects with mild to moderate AD (FDA 
Classification of Stage 2 to 4 AD [protocol APPENDIX 3]) and healthy adult subjects. Cohorts 1, 
2b, 3b, 4b, and 5b will include AD subjects (between the ages of 50 and 80 years, inclusive) and 
Cohorts 2a, 3a, 4a, and 5a will 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). In 
each of the 9 cohorts, subjects will be confined to the study site from Day -1 until Day 15.  
The study consists of 3 phases. 
1. Screening Phase – up to 28 days (from Days -28 to -1)  
2. Treatment Phase – 16 days:  
o Subjects will be admitted to the study site on Day -1. Subjects will receive 14 days 
of 3 times daily (TID) dosing with assigned study medication from Days 1 to 14 
and will remain confined until Day 15.  
o Each of the 9 cohorts will be initiated sequentially starting with Cohort 1 and 
progressing through to Cohort 5 depending on acceptable review of the safety data 
by a 3-member expert adjudication panel. Each of the Cohorts 2 to 5 will be sub-
divided into 2 cohorts: Cohorts 2a, 3a, 4a, and 5a will include healthy subjects and 
Cohorts 2b, 3b, 4b, and 5b will include AD subjects. The results from the healthy 
subject cohorts ‘a’ will be reviewed by the independent safety adjudication 
committee and if assessed as safe, the committee will permit progression to the 
corresponding 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 can 
proceed to the next higher dose level without having to wait for the corresponding 
AD subject cohort to be completed and reviewed by the safety adjudication panel. 
o The initiation of the next dose cohort may be delayed up to approximately 4 weeks 
following the last dose of the last subject in the preceding cohort. This is necessary 
to allow time for the safety and PK data to be compiled and tabulated for review by 
the safety committee (laboratory reports, AEs, tolerability, and PK data from all [up 
to 8] completed subjects in each cohort), to determine if it is safe to proceed with 
enrollment of the subsequent cohort. 
3. Follow-up Phase - 1 month  
o Subjects will be 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 patient will participate in the study for up to approximately 2.5 months. 
39


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 11 of 28 
3.2 
Treatments 
Cohort 1 will include 8 AD subjects (6 active and 2 placebo). Each of the Cohorts 2 to 5 will be 
sub-divided into 2 cohorts: Cohorts 2a, 3a, 4a, and 5a will include healthy subjects and Cohorts 2b, 
3b, 4b, and 5b will include AD subjects. For each cohort, subjects will be randomized to 1 of 2 
treatment groups in a 6:2 ratio of AL001 (active study medication) to placebo. Subjects in each of 
the cohorts will be dosed TID for 14 days at the dose level indicated in Table 2 below or placebo 
Active Group: Ascending doses of AL001 are manufactured in 210 mg 0 size capsules; the number 
of capsules for each cohort dosing will vary based on the AL001 dosing equivalent (refer to Table 
2 ). Dosing will be TID at approximately 8:00 AM, 2:00 PM, and 8:00 PM (within ±10 minutes). 
Patients will be fasted for each dose (dosed at least 1 hour before or 4 hours after meals).  
Placebo Group: The placebo capsules will be manufactured to appear exactly as the capsule used 
for AL001; the number of capsules dosed, number of doses, dosing schedule, and fasting 
conditions will be the same as for the active group. 
Table 2: Ascending Doses of AL001 for Each Cohort 
Cohort 
Daily Dosing Level 
No. of AL001 
210 mg Capsules 
AL001 Daily Dose 
Equivalent 
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. 
a.
Lithium dose equivalent to that used for bipolar/affective disorders.
3.3 
Study Procedures 
For complete details on the study assessments to be performed, refer to APPENDIX A. 
3.4 
Randomization and Blinding Procedures 
Subjects will be randomized by computer in a ratio of 6:2 (active:placebo) in each of the 9 cohorts. 
The randomization will be performed separately for AD subject cohorts and healthy subject 
cohorts. For the AD subject cohorts (Cohorts 1, 2b, 3b, 4b, and 5b) subjects will be randomized in 
a 6:2 ratio (active:placebo) and for the healthy subject cohorts (Cohorts 2a, 3a, 4a, and 5a), the 
randomization will be performed in such a way that age will be used as a stratification factor for 
each cohort: 3 non-elderly and 3 elderly subjects will receive AL001, and 1 non-elderly and 1 
elderly subject will receive placebo.  
40


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 12 of 28 
 
The subjects will be assigned a Screening Number (upon signing the informed consent at the 
Screening Visit) and a Subject Randomization Number (upon meeting eligibility criteria on Day 1) 
sequentially by the Investigator or authorized study staff. The Subject Randomization Numbers 
will start with 1001 for Cohort 1, 2001 for Cohort 2, etc. Prior to dosing on Day 1, the subject is 
assigned the next sequential randomization number for that cohort. Once a Subject Randomization 
Number is assigned to a subject, it will not be reused. The subject ID number will be the 
combination of the Screening Number and the Randomization Number.  
A key to the randomization will be kept secured by the Sponsor’s Medical Monitor or other 
Sponsor representative not involved in this study, in a sealed envelope under secure conditions at 
the study site for emergency use. In the occurrence of an SAE, or other safety issue which requires 
knowing the patient’s treatment group, the Medical Monitor will unblind that patient.  
3.5 
Sample size 
A maximum of 5 cohorts of 8 AD subjects each and 4 cohorts of 8 healthy subjects each will be 
enrolled in this clinical trial for a maximum total of 72 subjects. Each cohort will correspond to 
one of the 5 given dose level of AL001 and will be comprised of 6 subjects receiving AL001 and 2 
subjects receiving placebo. This sample size is not based on any statistical considerations, but is 
judged adequate to meet the primary objective of this clinical trial. 
 
 
41


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 13 of 28 
 
4 
ANALYSIS POPULATIONS 
The following analysis sets will be defined: 
 Screened Analysis Set: The Screened Analysis Set will include all the subjects who have 
signed the inform consent form.  
 Randomized Analysis Set: The Randomized Analysis Set will include all subjects who are 
randomized within one of the cohorts. 
 Safety Analysis Set: The Safety Analysis Set will include all subjects in the Randomized 
Analysis Set who receive any dose of study drug. This analysis set will be utilized for all 
safety analyses. 
 Pharmacokinetic Analysis Set: The PK Analysis Set will include all subjects in the Safety 
Analysis Set who receive AL001 and have either a Cmax measurement for salicylate or a 
trough measurement for lithium. This analysis set will be utilized for all PK analyses. 
 
 
42


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 14 of 28 
5 
STUDY SUBJECTS 
Disposition data, analysis population information, and protocol deviations will be listed 
and summarized as described in Table 3.   
Table 3: Data Presentations for Study Subject Information 
Data 
Variables 
Presentation 
Disposition and analysis 
population 
Subject, completion status (i.e., 
completed or withdrawn), reason for 
withdrawal, analysis set determination 
Listings: 
Randomization
Disposition
Analysis set
Table: 
Disposition
Protocol deviations 
Protocol deviations 
Listings: 

Protocol deviations
5.1 
Disposition 
Subject disposition will be summarized for all subjects randomized. The following will be 
presented: 

Number of subjects (N) screened

N of subjects randomized

N and % of subjects who completed the study

N and % of subjects who withdrew from the study by primary reason for withdrawal

N and % of subjects included in each analysis set
The percentages will be calculated using the number of randomized subjects as the denominator. 
The summary will be presented by treatment (dose level of AL001, pooled placebo and overall) 
for AD cohorts and Healthy cohorts.  
5.2 
Protocol Deviations 
Deviations identified at the site will be collected in the clinic deviation tracking system (DTS) and 
presented in a protocol deviation listing. Protocol deviations will be reviewed by the Sponsor, 
principal investigator, and lead statistician and finalized before unblinding the study. Protocol 
deviations will be listed for the safety population. 
43


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 15 of 28 
6 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Unless otherwise specified, all available data will be listed, summarized, for demographics and 
other baseline characteristics, and presented for all study population as detailed in Table 4. 
The screened analysis set will be used for exploratory analysis. 
Table 4: Data Presentations for Demographic and Other Baseline Characteristics 
Data 
Variables 
Presentation 
Demographic and Other 
Baseline Characteristics 
Sex, age, ethnicity, race, height, 
weight and body mass index (BMI), 
Mini-Mental State Examination 
(MMSE) scores, and AD stage FDA 
classification for AD subjects only 
Listing 
Table – presented for all study 
populations (Screened, 
Randomized, Safety and PK). 
Medical history 
All medical history findings 
Listing 
Prior and Concomitant 
medications 
All medications taken prior to 
study drug administration 
and concomitant medications 
Listing 
44


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 16 of 28 
 
7 
PHARMACOKINETIC ANALYSES 
7.1 
Pharmacokinetic Statistical Methodology 
All PK tables, figures and listings (TFLs), when appropriate, will be stratified by treatment and 
cohort for each study part.  
7.2 
Summary Statistics 
In order to characterize the MTD of AL001 in subjects with AD and healthy subjects, descriptive 
statistics will be presented by treatment group for each cohort and overall for the following: 
o Proportion of healthy non-elderly subjects with trough lithium concentrations > 1.2 mEq/L 
o Proportion of subjects with peak (Cmax) salicylate concentrations > 30 mg/dL 
o Proportion of healthy elderly and, separately, Alzheimer’s subjects with plasma trough 
measurements of lithium  > 1.0 mEq/L 
Summary statistics of the plasma concentration data will be calculated for the PK population, 
unless otherwise indicated. Summary statistics will be calculated for concentration at each 
individual time point.  
Concentration data will be 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), standard deviation (SD), geometric mean, minimum (min), median, 
maximum (max), and coefficient of variation (CV%).  
7.3 
Statistical Analysis 
In order to assess whether PK steady state has been approximately achieved, descriptive statistics 
for trough (Cmin) measurements of plasma lithium and Cmax (peak) measurements of plasma 
salicylate will be presented for all available days  by cohort and overall. In addition, these 
measurements for plasma lithium and salicylate on Days 13 and 14 for each cohort will be loge-
transformed and a 90% CI for the difference in the measurements between Days 13 and 14 for 
lithium and salicylate will be calculated on the loge scale and then transformed back to the original 
scale for each cohort. If the 90% CI on the original scale is contained within the interval 85.0% to 
117.6%, then an approximation of steady state will be concluded for the respective analyte and 
cohort. Alternative approaches to estimate achievement of steady-state conditions are to be used, 
as appropriate, such as when at least 3 trough concentrations for plasma lithium and/or at least 3 
Cmax concentrations for plasma salicylate can be assessed using linear regression. All cohorts 
except Cohort 1 are expected to complete at least 3 lithium trough and 3 salicylate peak 
concentration  measurements and should be candidates for this statistical approach. 
 
45


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 17 of 28 
8 
SAFETY ANALYSIS 
Unless otherwise specified, all available data will be listed and summary tables for safety 
assessments will be presented by treatment (dose level of AL001 and pooled placebo) per cohort 
for the safety population as detailed in Table 5.  
Continuous variables will be summarized (absolute values and change from baseline) using 
descriptive statistics (n, mean, SD, minimum, median and maximum). 
Table 5: Data Presentations for Safety Assessments 
Data 
Variables 
Presentation 
Adverse events 
Adverse event (AE) 
description, date and time (start 
and end), 
intensity, relationship to study 
drug, action taken, study days 
and outcome 
Listing 
Table 
Extent of 
exposure 
Study drug administration dose, 
units, date, time, cohort 
Listing 
Clinical 
laboratory 
evaluations 
Laboratory results (refer to section 
8.3 for parameters) 
Listing 
Table 
Vital signs 
Blood pressure, pulse, and body 
temperature 
Listing 
Table 
Physical 
examinations 
Physical examinations findings 
Listing 
12-Lead ECGs 
ECG interpretations and findings 
Listing 
Table 
8.1 
Adverse Events 
Treatment-emergent adverse events (TEAEs) are AEs that are not present prior to the exposure to 
study treatment. All AEs reported following exposure to study treatment are considered TEAEs.  
All TEAEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 25.0. The listing and summaries will include coded System Organ Class (SOC) and 
Preferred Term (PT). 
An overall summary by treatment (dose level of AL001 and pooled placebo and overall) will 
present the number and percentage of subjects with: 

At least one TEAE

At least one drug-related TEAE

Severity intensity
o Mild
o Moderate
46


Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 18 of 28 
o Severe
o
Life-threatening
o
Death

at least one SAE

at least one drug-related SAE

death
For the study, the following AE tables will also be presented: 

TEAEs by SOC and PT

SAEs by SOC and PT

Drug-related TEAEs by SOC and PT

TEAEs by SOC, PT, and maximum intensity

TEAEs that lead to premature discontinuation
Events will be listed by treatment, subject and AE onset date. Treatment-emergent AE duration 
(stop date/time - start date/time) will be included in the listing. 
8.2 
Adverse Events of Special Interest (AESI) 
Adverse events of special interest (AESI) for this study is upper gastrointestinal upset (lower 
gastrointestinal; diarrhea). The number and percentage of subjects with an AESI, as well as the 
total number of AESIs, will be summarized for each cohort and overall by SOC and PT. 
8.3 
Clinical Laboratory Evaluations 
Laboratory data will be presented using units as reported by the clinical laboratory. Specific 
hematology, chemistry, and urinalysis parameters are listed in Table 6. 
Table 6: Clinical Laboratory Evaluations 
Hematology 
Serum chemistry 
Complete blood count including: 
Red blood cells (RBCs), hemoglobin, hematocrit, 
reticulocytes, mean corpuscular volume, mean 
corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, platelet count 
White blood cell (WBC) count with differential 
including (absolute and percentage): 
neutrophils, lymphocytes, monocytes, eosinophils, 
basophils, band neutrophils 
HbA1ca 
Albumin 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Alkaline phosphatase (ALP) 
Blood Urea Nitrogen (BUN) or Urea 
Bicarbonate 
Creatinine 
Electrolytes (Na, K, Cl, Ca, P) 
Glucose (fasting) 
Lactate dehydrogenase (LDH) 
Total bilirubin 
Direct bilirubin 
Total cholesterol,  
High-density lipoprotein (HDL)c 
Low-density lipoprotein (LDL)c 
Triglyceridesc 
TSHa 
Mg 
Vitamin B12a 
Urinalysis 
47


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 19 of 28 
 
Urobilinogen  
Glucose  
Ketones  
Bilirubin  
Protein  
Nitrate 
Leukocytes 
Blood 
pH 
Specific gravity 
Abbreviations: TSH = thyroid-stimulating hormone. 
a. Performed at Screening and Day 23 or early termination only. 
b. Urobilinogen may be measured via a urine dipstick test at the site if their local laboratory does not include it in 
their urinalysis panel. 
c. 
Lipid panel (total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides) measured at 
the Screening Visit does not need to be repeated on Day -1. 
Absolute values for continuous parameters (hematology, general biochemistry, and urinalysis) will 
be summarized using descriptive statistics by each cohort (dose level of AL001 and pooled 
placebo; overall) and change from baseline will be presented.  
Number (Percentage) of Subjects with Normal, Abnormal Clinically Significant (CS) and 
Abnormal Non-Clinically Significant (NCS) values will be presented for each laboratory category 
by each cohort (dose level of AL001 and pooled placebo, overall) and visit. 
Serology, alcohol/drug screen, pregnancy test results will be presented in separate listings. 
Data listings will include out-of-range flags (Low, High) and whether the abnormal values are 
clinically significant or not. 
8.4 
Vital Signs 
Vital signs will include heart rate, blood pressure, and body temperature. 
Absolute values in vital signs measurements will be summarized descriptively by each cohort 
(dose level of AL001 and pooled placebo; overall), time point and change from baseline will be 
presented.  
Number (%) of subjects with Normal, Abnormal Clinically Significant (CS) and Abnormal Non-
Clinically Significant (NCS) values of vital signs will be presented by each cohort (dose level of 
AL001 and pooled placebo, overall), visit and time point. 
Data listing will identify if values are “abnormal, clinically significant” or “abnormal, not 
clinically significant”. Vital sign results will be presented. 
8.5 
Physical Examination Findings 
The physical examination will include a general review of the following body systems (at 
minimum): general appearance, head and neck, cardiovascular, respiratory, abdomen, and brief 
neurological examination. 
Physical examination results will be listed as normal or abnormal. Abnormal findings of clinical 
significance will be included in the listing.  
48


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 20 of 28 
 
8.6 
12-lead Electrocardiogram  
12- Lead safety ECG results will be summarized descriptively by each cohort ((dose level of 
AL001 and pooled placebo, overall), time point and change from baseline will be presented. 
Number (%) of subjects with Normal, Abnormal Clinically Significant (CS) and Abnormal Non-
Clinically Significant (NCS) values of ECG will be presented by each cohort (dose level of AL001 
and pooled placebo, overall), visit and time point. 
Data listing will identify if values are “abnormal, clinically significant” or “abnormal, not 
clinically significant”.  
 
 
49


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 21 of 28 
 
9 
DATA HANDLING AND PRESENTATION 
All safety and statistical outputs will be generated using SAS software, version 9.4. 
All programs used to generate statistical analyses will be validated according to Altasciences’s 
standard operating procedure (SOPs). 
Tables, figures and listings will be provided in RTF formats. 
9.1 
Safety Analysis Presentation 
Adverse events and medical history will be classified using the MedDRA terminology as defined 
in the study data management plan (DMP).  
Prior and concomitant medications will be coded with the World Health Organization drug 
dictionary (WHO-DD) (March 2022 B3) as defined in the study DMP. 
 
Generally, summaries will be presented by cohort (dose level of AL001 and pooled placebo, 
overall). Some summaries will also be presented to include overall (i.e., subject disposition and 
demographics).  
Summaries for data collected at scheduled times specified in the protocol will be presented by 
cohort (dose level of AL001 and pooled placebo, overall), visit, and, where applicable, time point. 
Continuous variables will be summarized using the number of observations, mean, standard deviation, 
minimum, median, and maximum. Categorical variables will be summarized using the number of 
observations and the corresponding percentage. 
In general, the data listings will include data from all subjects who receive at least one dose of 
either AL001 or placebo.  
Study days will be included in adverse event and concomitant medication listings in addition to 
dates. Study days will be calculated relative to the first day of double-blind treatment (Day 1) 
derived as (event date - first day of AL001 or placebo dosing) +1 for events after the first day of 
dosing and (event date - first day of AL001 or placebo dosing) for events before the first day of 
dosing. 
The following general comments also apply to all statistical analyses and data presentations: 
 Duration variables will be calculated using the general formula: (end date - start date) +1. 
 If the reported value of a clinical laboratory parameter cannot be used in a statistical 
summary table (e.g., a character string is reported for a parameter of the numerical type), a 
coded value must be appropriately determined and used in the statistical analyses.  In 
general, a value or lower and upper limit of normal range such as ‘<10’ or ‘≤5’ will be 
treated as ‘10’ or ‘5’ respectively, and a value such as ‘>100’ will be treated as ’100’.  
However, the actual values as reported in the database will be presented in data listings. 
 When assessments are repeated for a given time point or performed at unscheduled times, 
only the result which is the closest to the dosing time will be included in summary tables. 
In general, summary statistics for raw variables (i.e., variables measured at the study site or central 
laboratory) will be displayed as follows:  
50


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 22 of 28 
 
 Minima and maxima will be displayed to the same number of decimal places as the raw 
data.  
 Means, medians, and quartiles will be displayed to 1 additional decimal place.  
 Standard deviations will be displayed to 2 additional decimal places.   
 Percentages will be displayed to 1 decimal place. Percentages between 0 and 0.1 
(exclusive) will be displayed as ‘<0.1’.   
 P-values will be displayed to 3 decimal places. P-values that are less than 0.001 will be 
displayed as ‘<0.001’ if applicable. 
The number of decimal places for summary statistics of derived variables (i.e., variables that are 
not measured by the study site but are calculated for analysis based on other measured variables) 
will be determined on a case by case basis.  In general:  
 Minima and maxima will be displayed to the commonly used unit of precision for the 
parameter.  
 Means, medians, quartiles, and confidence limits will be displayed to 1 additional decimal 
place.  
 Standard deviations will be displayed to 2 additional decimal places.  
9.2 
Baseline 
The baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) 
collected before the first dose of study drug in each cohort. 
 
51


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 23 of 28 
 
10 INTERIM ANALYSES AND DATA SAFETY MONITORING 
There is no interim analysis plan for this study. 
 
52


 
 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 24 of 28 
 
11 GENERAL INFORMATION RELATED TO DATA PRESENTATIONS 
The formats and layouts of TFLs are provided in a separate document and are common displays.  
Their numbering and general content follow the International Conference on Harmonisation (ICH) 
E3 guidelines.  Actual formats and layouts may be altered slightly from those presented as 
necessary to accommodate actual data or statistics.  
Minor format changes will not require updates to the SAP; rather they may be documented in a 
Note to SAP. 
53


Protocol Number: AL001-ALZ02 
Alzamend Neuro, Inc. 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
 
APPENDIX A STUDY SCHEDULE(S) 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Informed Consent 
X 
Admission1 
X 
Clinic Confinement 
X 
X 
Discharge 
X 
Medical and Surgical History 
X 
Physical Examination 
X 
X 
X 
X 
Demographic information 
X 
Body Height/Body Weight 
X 
Vital Signs2 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG3 
X 
X 
X 
X 
X 
X 
 
 
 
 
1 Subjects will be admitted to the clinical research unit at least 16 hours prior to the first study drug administration. 
2 Vital signs will include blood pressure, heart rate and oral body temperature. On Days 1 to 14, vital signs will be measured 
within 1 hour prior to dosing using the same arm, if possible, after 5 minutes in seated position. 
54


Protocol Number: AL001-ALZ02 
Alzamend Neuro, Inc. 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
 
 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Safety Laboratory Tests4 
X 
X 
X 
X 
X 
X 
Serology (HIV/HBV/HCV) 
X 
Serum Pregnancy Test (females 
of childbearing potential only) 
X 
Urine Pregnancy Test (females 
of childbearing potential only) 
X 
COVID-19 Test5 
X 
X 
Urine Drug Screen and Alcohol 
Breath or Urine Test 
X 
X 
Inclusion/Exclusion Criteria 
X 
X 
Randomization 
X 
Fasted Study Drug 
X 
X 
 
 
3 On Day 1, ECGs will be conducted pre-dose and 1 hour (±10 minutes) after the third dose of Day 1. On Days 7, 13, and 14, ECGs will be performed prior to 
first daily dose. 
4 Safety laboratory tests (chemistry, hematology, and urinalysis) will be performed on Day -1, Day 7 (pre-dose), Day 15, and Day 23. For all subjects, 
total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides will not be included in the safety laboratory tests performed on Day 
-1. For subjects who are screened within 5 days of check-in (on Day -6 to Day -2), the safety laboratory tests will not be performed on Day -1. 
5 The COVID-19 test should be repeated upon check-in on Day -1 using a COVID rapid antigen test kit or PCR. Additionally,, study site and local health 
authority policies and recommendations can be applied for compliance. If the initial result is positive at the Screening Visit, the test may be repeated after 14 
days or on Day -1 whichever comes first. 
55


Protocol Number: AL001-ALZ02 
Alzamend Neuro, Inc. 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
 
 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Administration (all doses) 
Baseline and Trough plasma 
lithium and peak plasma 
salicylate concentration 
measurements6 
X 
X 
X 
MMSE Score (AD subjects 
only) 
X 
Hachinski Ischemic Scale 
Score7 (AD subjects only) 
X 
Meals8 
X 
X 
X 
X 
 
 
 
6 Blood samples for baseline plasma lithium and plasma salicylate concentration measurements will be collected before first dose on Day 1. Blood samples for 
trough plasma lithium and peak plasma salicylate concentration measurements will be collected on Days 3, 5, 7, 10, 13, and 14, and at the discretion of the 
Investigator (the latter are ‘Safety Samples’ for Therapeutic Drug Monitoring), particularly to assess the relationship to possible lithium or salicylate related 
AEs. These safety samples could be sent for expedited analysis to either a local laboratory with an aliquot saved for the bioanalytical laboratory, or to the 
bioanalytical laboratory directly (Sannova or Altasciences). In addition, for AD subject Cohorts 2b, 3b, 4b, and 5b, the trough lithium sample on Day 5 will be 
treated as a ‘Safety Sample’ for Therapeutic Drug Monitoring to assess any lithium-related PK exposure safety concerns at an early treatment time point which 
may require dosing to be discontinued for an individual subject. This sample will be sent to Sannova for expedited analysis. Similarity between Days 13 and 14 
trough lithium plasma levels and peak salicylate plasma levels will be used to determine the status of lithium and salicylate steady-state PK conditions, and/or 
by another appropriate method, such as linear regression. Blood collection for trough lithium plasma concentrations will occur just prior to the first daily dose, 
while blood collection for peak plasma salicylate concentrations will occur at 1.25 hours post third daily dose (the estimated time to a maximum blood 
concentration Cmax). For early termination, blood samples for lithium and salicylate plasma concentrations will be collected. A ±10-minute window will be 
allowed for collection of PK samples for both lithium and salicylate. 
7 Hachinski Ischemic Scale Score is presented in protocol APPENDIX 5. 
56


 
 
 
Protocol No. AL001-ALZ02|Altasciences Project No. ALZ-P9-319| Version Final 1.0 | 2023/02/22 
Page 28 of 28 
 
Study Procedures 
Screening 
(28 days prior to 
randomization) 
In-patient 
admission 
Treatment 
Period 
Clinic 
Discharge 
Follow-up Period 
Early 
Termination 
(ET) 
Study Day 
Days -28 to -1 
Day -1 
Day 1 
Days 2 
to 14 
Day 15 
Day 23 ±1 day 
Clinic Visit 
Day 42 ±2 days 
Telephone call 
Adverse Event 
Reporting/Safety-Tolerability 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
Prior Medications 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Health Status Questionnaire 
(SF-36) 
X 
X 
X 
Abbreviations: AD = Alzheimer’s disease; COVID-19 = Coronavirus Disease 2019; ECG = electrocardiogram; ET = Early Termination; HBV = hepatitis B 
virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; MMSE = Mini-Mental State Exam; PK = pharmacokinetic(s); TSH = thyroid-stimulating 
hormone 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 Meals during confinement should include breakfast (at least 1 hour after first dose), lunch (at least 1 hour after second dose), dinner (at least 1 hour after 
third  dose), and a snack (if time permits and 10-hour fast is respected). On Day 15, breakfast will be provided prior to subject/caregiver being 
discharged from the study site. 
 
57