AL001 for Pharmacokinetics

Overseen By Eve del Rio, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Alzamend Neuro, Inc.

Must not be taking: Antipsychotics, MAO inhibitors

Disqualifiers: Kidney disease, Psychiatric illnesses, Seizure disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 28

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications, including over-the-counter drugs, vitamins, and herbal supplements, at least 14 days before the study begins and throughout the study period. However, hormonal contraceptives and acetaminophen (up to 1000 mg per day) are allowed.

What data supports the effectiveness of the drug AL001, which includes Lithium Carbonate, for its intended use?

Lithium carbonate is well-known for its effectiveness as a mood stabilizer in treating bipolar disorder, as it helps prevent mood swings. Studies show that it maintains steady levels in the body, which is important for its effectiveness and safety. ^{1 2 3 4 5}

Is lithium carbonate generally safe for humans?

Lithium carbonate has been studied for safety in humans and animals, showing no serious side effects in healthy volunteers and no reproductive or developmental toxicity in animal studies. However, it can cause toxicity at high doses, especially in cases of overdose, and requires careful monitoring of blood levels to avoid side effects. ^{1 3 6 7 8}

How is the drug AL001 different from other treatments for its condition?

AL001, which includes Lithium Carbonate, is unique because it combines lithium, a mood stabilizer often used for bipolar disorder, with a novel formulation that may offer different pharmacokinetic properties, such as absorption and distribution, compared to standard lithium treatments. This could potentially lead to improved efficacy or reduced side effects. ^{9 10 11 12 13}

What is the purpose of this trial?

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

Eligibility Criteria

Healthy adults aged 18-65, with a BMI of 18.0 to 30.0 kg/m2 and weight at least 50 kg, can join this trial. They must be in good health as confirmed by medical checks, understand English, and agree to use contraception if necessary. People with significant health issues or conditions that could affect the study's outcome cannot participate.

Inclusion Criteria

Willing to follow study procedures.

Able to communicate in English, including speaking, reading, and writing.

Able to understand and provide written informed consent.

Exclusion Criteria

Presence or history of any disorder that may prevent the successful completion of the study.

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.

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either AL001 or Lithium Carbonate for 14 days, including overnight stays and multiple MRIs and blood draws

2 weeks

14 days of overnight stays at MGH

Washout

Participants undergo a washout period between treatment sequences

2-4 weeks

Treatment Period 2

Participants receive the alternate treatment (AL001 or Lithium Carbonate) for 14 days, including overnight stays and multiple MRIs and blood draws

2 weeks

14 days of overnight stays at MGH

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AL001
• Lithium Carbonate Capsule

Trial Overview The trial is testing AL001, a new crystalized form of lithium against standard Lithium Carbonate capsules for safety and how it's processed by the body and brain. Participants will take each drug for two weeks while staying at a research unit for monitoring which includes MRIs and blood tests.

Participant Groups

Group I: Sequence 2: Lithium Carbonate then AL001 Experimental Treatment 2 Interventions

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.

Group II: Sequence 1: AL001 then Lithium Carbonate Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Alzamend Neuro, Inc.

Lead Sponsor

Trials

2

Recruited

100+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Findings from Research

In a study involving eight healthy volunteers, lithium carbonate showed a mean biological half-life of approximately 16.5 hours, indicating a slow disposition rate which is important for its therapeutic use.

The controlled release formulation of lithium carbonate resulted in a smoother serum concentration profile, with a 22% lower peak concentration and a delayed time to peak, suggesting it may provide a more stable delivery of the drug compared to the immediate release tablet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption and disposition kinetics of lithium carbonate following administration of conventional and controlled release formulations. Arancibia, A., Corvalan, F., Mella, F., et al.[2013]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Estimation of lithium clearance from routine clinical data in Egyptian bipolar patients. A population pharmacokinetic approach. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Absorption and disposition kinetics of lithium carbonate following administration of conventional and controlled release formulations. [2013]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

Intensive treatment with lithium carbonate "once a day" in bipolar patients. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

Distribution of lithium elimination rates in a selected population of psychiatric patients. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Single dose pharmacokinetics of 5 formulations of lithium: a controlled comparison in healthy subjects. [2019]

7. Ireland pubmed.ncbi.nlm.nih.gov

Lithium carbonate: Updated reproductive and developmental toxicity assessment using scientific literature and guideline compliant studies. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Unrecognized delayed toxic lithium peak concentration in an acute poisoning with sustained release lithium product. [2013]

9. Netherlands pubmed.ncbi.nlm.nih.gov

High-performance liquid chromatographic method for the determination of a potential memory-enhancing compound (CL 275,838) and its desbenzyl metabolite in rat plasma or serum. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of MDL 26479, a novel benzodiazepine inverse agonist, in normal volunteers. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Plasma Protein Binding Rate and Pharmacokinetics of Lekethromycin in Rats. [2022]

12. Singapore pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of laetispicine and its brain distribution in rats. [2010]

13. Germany pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and tolerability of alpidem in healthy subjects given increasing single doses. [2018]