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 Subjects With Bipolar I Disorder

NCT07540338 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AL001-BD01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to assess the safety and effects of a crystallized form of lithium, AL001, when compared to commonly used lithium carbonate in individuals diagnosed with bipolar I disorder. The main questions this study aims to answer are:

• How safe 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

Bipolar I Disorder

Keywords

Neurology; Psychiatry; Pharmacokinetics

Outcome Measures

Primary Outcomes (30)

• 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.

  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.

  Area under the plasma and brain concentration versus time curve (AUC) will be measured.

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma AUCtau ss = Area under the plasma concentration versus time curve from time zero to the end of the 24-hour 3-dose interval at steady-state

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain AUCtau ss = Area under the plasma concentration versus time curve from time zero to the end of the 24-hour 3-dose interval at steady-state

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma Cmax ss = Maximum plasma concentration at steady-state

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain Cmax ss = Maximum brain concentration at steady-state

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma tmax ss = Time to reach the maximum plasma concentration at steady-state

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain tmax ss = Time to reach the maximum brain concentration at steady-state

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma Cmin ss = Minimum plasma concentration at steady-state (if at end-of-24 hour dosing interval: Ctrough)

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain Cmin ss = Minimum brain concentration at steady-state (if at end-of-24 hour dosing interval: Ctrough)

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma tmin ss = Time to reach the minimum plasma concentration at steady-state over 24 hours

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain tmin ss = Time to reach the minimum brain concentration at steady-state over 24 hours

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain/Plasma AUCtau ss ratio = Ratio of brain/plasma areas under the plasma concentration versus time curve from time zero to the end of the 24-hour 3-dose interval at steady-state

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain/Plasma Cmax ss ratio = Ratio of brain/plasma minimum concentrations from time zero to the end of the 24-hour 3-dose interval at steady-state.

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain/Plasma Cmin ss ratio = Ratio of brain/plasma minimum concentrations from time zero to the end of the 24-hour 3-dose interval at steady-state.

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma apparent oral clearance (CLoral) = Dose24 hours/Plasma AUCtau ss

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

• To characterize AL001 lithium PK under the conditions of this study

  Average plasma concentration at steady-state (Css ave plasma) = Plasma 24 h AUCtau ss/24 hours

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

• To characterize AL001 lithium PK under the conditions of this study

  Average brain concentration at steady-state (Css ave brain) = Brain 24 h AUCtau ss/24 hours

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma degree of fluctuation at steady-state (FIplasma ss) = Ratio of plasma (Cmax ss - Cmin ss) to Css ave plasma

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain degree of fluctuation at steady-state (FIbrain ss) = Ratio of brain 24 h (Cmax ss - Cmin ss) to Css ave brain

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

• To characterize AL001 lithium PK under the conditions of this study

  Plasma swing 24 h = \[(Cmax ss - Cmin ss)/ Cmin ss \]

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

• To characterize AL001 lithium PK under the conditions of this study

  Brain swing 24 h = \[(Cmax ss - Cmin ss)/ Cmin ss \]

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

• To characterize AL001 lithium PK under the conditions of this study

  MRT oral doses (0-24h ss) = Mean Residence Time following oral doses at steady-state (0 to tau, end of 24-hour dosing interval)

  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 subjects with bipolar I disorder diagnosis 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(P2)

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in subjects with bipolar I disorder diagnosis under the conditions of this study.

  Proportion of participants with abnormal vital signs

  From enrollment to Day 23 (P2)

• To evaluate the safety and tolerability of AL001 under multiple-dose, steady-state conditions in subjects with bipolar I disorder diagnosis 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 subjects with bipolar I disorder diagnosis 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 subjects with bipolar I disorder diagnosis 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 subjects with bipolar I disorder diagnosis 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 subjects with bipolar I disorder diagnosis under the conditions of this study.

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

  From enrollment to Day 23 (P2)

Secondary Outcomes (11)

• To characterize AL001 salicylic acid PK under the conditions of this study

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

• To characterize AL001 salicylic acid PK under the conditions of this study

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

• To characterize AL001 salicylic acid PK under the conditions of this study

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

• To characterize AL001 salicylic acid PK under the conditions of this study

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

• To characterize AL001 salicylic acid PK under the conditions of this study

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

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

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

Interventions

AL001 DRUG

Crystallized lithium

Also known as: lithium salicylate/L-proline cocrystal

Sequence 1: AL001 then lithium carbonate; Sequence 2: Lithium carbonate then AL001

Lithium carbonate DRUG

Lithium carbonate

Sequence 1: AL001 then lithium carbonate; Sequence 2: Lithium carbonate then AL001

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with Bipolar I Disorder (BD1) between the age of ≥ 18 and ≤65 years who are in reasonably good physical health, as determined by a DSM-5-TR BD1 diagnosis and 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 (HDRS-17) rating of \< 16 at the Screening visit and on Day -1 (P1). Subsyndromal depression has not significantly worsened in the 4 weeks prior to randomization on Day -1 (P1) so as to avoid enrolling subjects who are on the verge of a full depressive episode. 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.
• Clinically acceptable, stably dosed mood stabilizing medication regimen, including treatment regimens with atypical antipsychotic drugs, for \> 30 days prior to Screening visit, with no medication changes planned over the entire study period. See Section 6.3 for a list of medications not allowed for mood stabilization purposes. Exceptions to this may be made on a case-by-case basis following agreement by the Investigator and the Sponsor. Also, subjects with untreated BD1 can be enrolled if deemed adequately stable by the Investigator.
• 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 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 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 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)

You may not qualify if:

• Clinically significant abnormalities detected by medical history, physical examination, vital sign measurements, ECG findings (including prolonged QT interval), 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 or asthma (with the exception of childhood asthma), urticaria or other severe allergic diathesis.
• Presence or history of any disorder other than the diagnosis under study 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.
• Severe hepatic impairment (Child-Pugh Class C).
• Uncontrolled hypertension with a sustained blood pressure \> 160/100 mmHg at Screening, or at check-in on Day -1 (P1).

Sponsors & Collaborators

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

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Interventions

Lithium Carbonate

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Eve del Rio, MD, PhD

CONTACT

(908) 672-6388; eve@riopharma.com

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 17, 2026
• First Posted: April 20, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)