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

1. 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.

2. Well defined diagnosis of drug sensitives with moderate to severe reactions (i.e., full body urticaria, reactions requiring hospitalization, etc.).

3. Presence or history of any disorder other than the diagnosis under study that may prevent the successful completion of the study.

4. 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.

5. History of seizure disorder and/or severe head trauma (other than a single childhood febrile seizure).

6. Current uncontrolled gastrointestinal disease of moderate to severe nature such as chronic gastritis, peptic ulcers, inflammatory bowel disease, hemorrhagic gastritis, or duodenitis.

7. History or presence of acute or chronic liver disease as determined by the Investigator.

8. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study treatments.

9. Current treatment with migraine medications such as triptans, TCAs, or other serotonergic dominant medications.

10. Kidney disease (eGFR \< 60 mL/minute/1.73 m2).

11. Uncontrolled tachy/brady arrhythmias, atrial fibrillation, or coronary heart failure.

12. Systemic related exclusions:

1. Active cancer (except squamous cell and basal skin cancers) requiring chemo- or radiation therapy.

2. Positive test results for HIV, HBV, or HCV (unless quantitative PCR negative for HCV) at Screening.

3. Severe hepatic impairment (Child-Pugh Class C).

4. Uncontrolled hypertension with a sustained blood pressure \> 160/100 mmHg at Screening, or at check-in on Day -1 (P1).

5. 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).

13. Secondary psychiatric or neurological illnesses other than-and not associated with-bipolar I disorder (e.g., bipolar II disorder exclusively, schizophrenia or other psychotic syndromes, ADHD, anxiety, PTSD, Parkinson's disease and related movement disorders, seizure disorder, and myasthenia gravis) that require treatment with medications included in section 6.3.

14. Treatment with haloperidol, first generation antipsychotics, monoamine oxidase inhibitors, or neuromuscular blocking agents. Subjects who have ever received chronic immunosuppressant treatment (excluding topical or oral corticosteroids taken 1 year and 5 years before Screening, respectively).

15. Current and during lithium treatment hyponatremia, defined as serum sodium laboratory value outside the standard reference range.

16. The regular and long-term use of any medication, supplement, or OTC medication not approved by the Sponsor that can potentially interact with components of AL001 (outlined in section 6.3), within 14 days prior to the Screening visit or at least 6 times the respective elimination half-life, whichever is longer, through the completion of the study on Day 42 (P2). EXCEPTIONS to this include but are not limited to:

1. Hormonal contraceptives for females of childbearing potential.

2. Acetaminophen (up to 1000 mg TID) at the discretion of the Investigator.

3. Low-Dose aspirin for cardio protection.

4. Non-medicated ophthalmic products (for lubrication and comfort).

5. Clinically acceptable, stably dosed mood stabilizing medication regimen for \> 30 days prior to Screening visit, with no medication changes planned over the entire study period. See Section 6.3 for 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.

6. PRN medications needed for treatment of AE's during the study at the joint discretion of the Investigator and the Sponsor, reviewed on a case-by-case basis.

17. Subjects treated with electroconvulsive therapy within 6 months prior to Screening visit.

18. Unwilling to refrain from consumption of poppy seeds or quinine (tonic water) 48 hours prior to check-in on Day -1 (P1) until discharge from Period 2 treatment on Day 15 (P2).

19. Aspirin/nasal polyposis/asthma syndrome.

20. Female who is breastfeeding.

21. Female who is pregnant according to the pregnancy test at Screening or on Day -1 (P1); female planning to become pregnant during the study.

22. History of adverse or hypersensitivity reaction to lithium, aspirin, salicylate, L-proline, or any investigational or reference article excipient.

23. Substance Use Disorder (SUD) / Alcohol Use Disorder (AUD):

1. History of substance use (barbiturate, amphetamine, benzodiazepine, cocaine, opiates and cannabis) within the last 12 months or a positive urine drug screen at Screening or Day -1 (P1).

2. Admitted alcohol use disorder or history of alcohol use that may interfere with the subject's ability to comply with the protocol requirements or positive ethanol (alcohol) test at Screening or Day -1 (P1).

3. More than moderate current alcohol consumption. Subjects will be advised to consume no more than 2 units of alcohol per day and completely abstain from 72 hours prior to any study visit (1 unit is equal to approximately 10 g of pure alcohol, \[250 mL\] of beer \[5%\], 1 small glass \[100 mL\] of wine \[12%\], or 35 mL of spirits \[35%\]).

24. Demonstrating excess xanthine consumption (e.g., ingests more than 5 cups of coffee or equivalent per day). Also, subject is not willing to refrain from xanthine products for 48 hours prior to check-in on Day -1 (P1) until discharge from Period 2 treatment on Day 15 (P2). The subject is not willing to refrain from grapefruit, pomelo, Seville orange products or juice within 14 days prior to check-in on Day -1 (P1) until discharge from Period 2 treatment on Day 15 (P2). Exceptions may be made on a case-by-case basis following agreement by the Principal Investigator and the Sponsor.

25. Participation in a clinical trial and receipt of an investigational medication within 30 days or 5 half-lives (if known), whichever is greater, prior to the first dose of the current study drug.

26. Clinically unstable thyroid dysfunction (required due to potential lithium drug-disease interaction).

28. Subjects with any past apparent suicide attempt or suicidal behavior, within the past two years or a past year level 4 or higher SI/B (C-SSRS) or past month SI/B (C-SSRS) of any kind.

29. Suspected of having or at risk for Brugada Syndrome.

30. Central nervous system-related exclusions: Any medical condition that in the Investigator's judgement could affect subject safety and scientific integrity of the study, e.g., untreated hypothyroidism (TSH \>10 mIU/L) or vitamin B12 deficiency (vitamin B12 \<300 pg/mL) which may contribute to cognitive impairment, delirium, dementia and other encephalopathies.

What this study is about