A Randomized, Balanced, Phase 1/2A, Multiple-dose, Open-label, Two-treatment, Two-period, Two-sequence, Crossover, Relative Bioavailability 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
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Alzamend Neuro, Inc.
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- To evaluate differences in brain and/or brain structure lithium PK relative to plasma PK for AL001 capsule compared to a lithium carbonate capsule.
Overview
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.
Detailed Description
This study is researching the effects of a new type of crystallized lithium, AL001, on it's ability to reach the brain and have an effect in subjects with bipolar I disorder diagnosis. The investigators will be comparing this to a commonly used type of lithium, lithium carbonate. Investigators want to see if the AL001 can have the same or better effect when compared to lithium carbonate. Past research has shown a greater effect within the body with AL001 when compared to commonly used lithium.
This past research suggests that AL001 may be more effective, potentially allowing for lower doses and fewer side effects. If successful, this new form of lithium could offer a new and safe treatment option for psychiatric and neurological disorders.
This study involves two, 2-week long overnight stays at the main campus of Massachusetts General Hospital (MGH). During these stays, participants will receive lithium carbonate for one stay and the AL001 for the other. There are frequent blood draws and brain MRI scans during two periods of the study to look at how the AL001 is broken down in the body and to see how it reaches the brain. This study will compare AL001 to a study reference treatment of lithium carbonate. The majority of the blood draws and MRIs will occur over a 24 hour period during each 2-week long overnight stay at MGH.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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:
Exclusion Criteria
- •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).
Arms & Interventions
Sequence 1: AL001 then lithium carbonate
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.
Intervention: AL001 (Drug)
Sequence 1: AL001 then lithium carbonate
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.
Intervention: Lithium carbonate (Drug)
Sequence 2: Lithium carbonate then AL001
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.
Intervention: AL001 (Drug)
Sequence 2: Lithium carbonate then AL001
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.
Intervention: Lithium carbonate (Drug)
Outcomes
Primary Outcomes
To evaluate differences in brain and/or brain structure lithium PK relative to plasma PK for AL001 capsule compared to a lithium carbonate capsule.
Time Frame: From time zero to the end of the 24 hour 3-dose interval at steady state.
Brain (and brain structures)-to-plasma ratios between AL001 and lithium carbonate for steady-state PK measures/ parameters.
To characterize AL001 lithium PK under the conditions of this study
Time Frame: From time zero to the end of the 24 hour 3-dose interval at steady state.
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
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.
Time Frame: From enrollment to end of follow-up period at Day 42(P2)
Proportion of participants with adverse events and serious adverse events
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.
Time Frame: From enrollment to Day 23 (P2)
Proportion of participants with abnormal vital signs
Secondary Outcomes
- 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.)
- Exploring Brain Pharmacodynamics using Magnetic Resonance Spectroscopy(From Screening (Day 1) to Day 23 (P2))