A Study to Investigate Lithium Brain/Plasma Pharmacokinetics and Safety of an AL001 Oral Capsule Compared to a Marketed Immediate-release Lithium Carbonate Capsule in Healthy Adult Subjects

NCT06921590 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AL001-ALZ03
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to assess the safety and effects of a crystalized form of lithium, AL001, when compared to commonly used Lithium Carbonate in healthy volunteers. The main questions this study aims to answer are: How safe and effective is AL001 when compared to Lithium Carbonate? How is AL001 broken down in the brain and body compared to Lithium Carbonate? Participants will be asked to:

• Take both the study drug (AL001) and Lithium Carbonate each for a period of 14 days
• Stay overnight at MGH's research unit for two separate 2-week periods
• Participate in two separate 24 hour periods of multiple MRIs and blood draws

Conditions

Pharmacokinetics; Neurology

Keywords

Healthy Controls

Outcome Measures

Primary Outcomes (9)

• To evaluate differences in brain and/or brain structure lithium PK relative to plasma PK for AL001 capsule compared to a lithium carbonate capsule.

  • Brain (and brain structures)-to-plasma ratios between AL001 and lithium carbonate for steady-state PK measures/ parameters Area under the plasma and brain concentration versus time curves (AUC) will be measured.

  From time zero to the end of the 24 hour 3-dose interval at steady state

• To evaluate differences in brain and/or brain structure lithium PK relative to plasma PK for AL001 capsule compared to a lithium carbonate capsule.

  • Similarities and differences between steady state brain and brain structures lithium PK measures/parameters for AL001 and lithium carbonate Area under the plasma and brain concentration versus time curves (AUC) will be measured.

  From time zero to the end of the 24 hour 3-dose interval at steady state

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in healthy adult subjects under the conditions of this study.

  Proportion of participants with adverse events and serious adverse events

  From enrollment to end of follow-up period at Day 42

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in healthy adult subjects under the conditions of this study.

  Proportion of participants with abnormal vital signs (from baseline to Day 23 (P2))

  From enrollment to Day 23 (P2)

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in healthy adult subjects under the conditions of this study.

  Proportion of participants with abnormal values and change from baseline reading for each ECG parameter. Individual parameters including heart rate, PR, QT, QTcF, QRS, and RR intervals will be collected.

  From enrollment to Day 23 (P2)

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in healthy adult subjects under the conditions of this study.

  Proportion of participants with abnormal findings on physical exam.

  From enrollment to Day 23 (P2)

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in healthy adult subjects under the conditions of this study.

  Proportion of participants with abnormal values and changes from baseline for each Safety laboratory test (standard hematology, blood chemistry \[clinical chemistry\], urinalysis, and pregnancy test \[for females of childbearing potential only).

  From enrollment to Day 23 (P2)

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in healthy adult subjects under the conditions of this study.

  Proportion of participants with prevalence of plasma lithium concentrations above 1.2 mEq/L.

  From enrollment to Day 23 (P2)

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in healthy adult subjects under the conditions of this study.

  Proportion of participants with prevalence of plasma salicylate concentrations above 30 mg/dL

  From enrollment to Day 23 (P2)

Secondary Outcomes (3)

• To characterized AL001 salicylate PK under the conditions of this study

  From time zero to the end of the 24 hour 3-dose interval at steady state.

• To characterized AL001 salicylate PK under the conditions of this study

  From time zero to the end of the 24 hour 3-dose interval at steady state.

• Exploring Brain Pharmacodynamics using Magnetic Resonance Spectroscopy

  From Screening (Day 1) to Day 23 (P2)

Study Arms (2)

Sequence 1: AL001 then Lithium Carbonate

OTHER

Participants take 1050 mg of AL001 TID for 14 days then after a washout period, take 150 mg TID of Lithium Carbonate for 14 days.

Drug: AL001; Drug: Lithium Carbonate Capsule

Sequence 2: Lithium Carbonate then AL001

OTHER

Participants take 150 mg of Lithium Carbonate TID for 14 days, then after a washout period, take 1050 mg of AL001 TID for 14 days.

Drug: AL001; Drug: Lithium Carbonate Capsule

Interventions

AL001 DRUG

Crystalized Lithium

Also known as: lithium salicylate/L-proline cocrystal

Sequence 1: AL001 then Lithium Carbonate; Sequence 2: Lithium Carbonate then AL001

Lithium Carbonate Capsule DRUG

Lithium Carbonate

Sequence 1: AL001 then Lithium Carbonate; Sequence 2: Lithium Carbonate then AL001

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects ≥18 and \<65 years old in reasonably good physical and psychological health as determined by the Investigator's review of medical and surgical history, physical examination (including neurological examination), 12-lead ECG, vital signs, and clinical laboratory tests.
• Assessment of subject's mental health status will be conducted to avoid enrolling subjects who are on the verge of a manic or depressive episode. Affective stability, defined by a Young Mania Rating Scale (YMRS) rating of \<8 and a Hamilton Depression Rating Scale (HRSD-17) rating of ≤7 at screening and baseline. Assessment of subject's suicidal ideation and behavior (SI/B) using the Columbia-Suicide Severity Rating Scale (C SSRS) will be conducted to avoid enrolling subjects with concerning results, defined as a lifetime history of a suicide attempt, past year level 4 or higher suicidal ideation on the C-SSRS, or past month suicidal ideation of any kind. The "Lifetime/Recent" version will be used at screening and the "Since Last Visit" version will be used subsequently.
• Able to understand and follow instructions during the study as determined by the Investigator.
• Willing to follow study procedures.
• Willing and able to adhere to study restrictions and to be confined at the clinical research center per protocol requirements.
• Any gender, race, or ethnicity.
• Able to understand and provide written informed consent.
• Males (non-vasectomized and vasectomized) must agree to use barrier contraception during the study until after Treatment Period 2 in-clinic follow-up visit on Day 23 (P2).
• Females must meet one the of the following criteria:
• Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:
• Abstinence from heterosexual intercourse from the Screening visit through to at least 30 days after the last dose of the second study drug on Day 14 (P2).
• One of the following highly-effective contraceptive methods, used from at least 28 days prior to the Screening visit through to at least 30 days after the last dose of the second study drug on Day 14 (P2).
• i. Systemic contraceptives (combined birth control pills, injectable/implant/ insertable hormonal birth control products, or transdermal patch).
• ii. Intrauterine device (with or without hormones). iii. Male partner vasectomized at least 6 months prior to the Screening visit. c. One of the following double-barrier contraceptive methods, used from the Screening visit through to at least 30 days after the last dose of the second study drug on Day 14 (P2): i. Male condom used simultaneously with diaphragm plus spermicide. ii. Male condom used simultaneously with cervical cap plus spermicide. Or Is of non-childbearing potential, defined as surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or is in a postmenopausal state (i.e., at least 1 year without menses prior to the Screening visit).
• Able to communicate in English, including speaking, reading, and writing.

You may not qualify if:

• Clinically significant abnormalities detected by medical history, physical examination, vital sign measurements, ECG findings, or clinical laboratory findings (as determined by the Investigator) that may affect the safety or successful participation of the subject. Specifically, evidence of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, dermatologic, muscular, or allergic disease or disorder (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) that may affect the safety or successful participation of the subject. Any history of drug hypersensitivity, asthma (with the exception of childhood asthma), urticaria or other severe allergic diathesis.
• Presence or history of any disorder that may prevent the successful completion of the study.
• Other severe acute, chronic, or historical medical or psychiatric condition or laboratory abnormality or social circumstance that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
• History of seizure disorder and/or severe head trauma (other than a single childhood febrile seizure).
• History or presence of gastrointestinal disease including chronic gastritis, peptic ulcers, inflammatory bowel disease, hemorrhagic gastritis, or duodenitis.
• History or presence of acute or chronic liver disease as determined by the Investigator.
• Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study treatments.
• Any history of frequent headache or migraine.
• Kidney disease (eGFR \<60 mL/minute/1.73 m2).
• Uncontrolled tachy/brady arrhythmias, atrial fibrillation, or coronary heart failure.
• Active cancer (except squamous cell and basal skin cancers) requiring chemo- or radiation therapy.
• Positive test results for HIV, HBV, or HCV (unless quantitative PCR negative for HCV) at Screening.
• Uncontrolled hypertension with a sustained blood pressure \>160/100 mmHg at Screening, or at check-in on Day -1 (P1).
• Fever (body temperature \>101.4°F \[38.5°C\]), acute upper respiratory, or any other infections at Screening, or at check-in on Day -1 (P1).
• Psychiatric or neurological illnesses (e.g., depression, schizophrenia or other psychotic syndromes, Parkinson's disease and related movement disorders, seizure disorder, and myasthenia gravis).

Sponsors & Collaborators

• Alzamend Neuro, Inc.: lead
• Massachusetts General Hospital: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Interventions

Lithium Carbonate

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2025
• First Posted: April 10, 2025
• Study Start: May 9, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 9, 2025

Record last verified: 2025-04

Locations

US (1)