Neurology, Pharmacokinetics
Conditions
Keywords
Healthy Controls
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
Detailed description
This study is researching the effects of a new type of crystalized lithium, AL001, on it's ability to reach the brain and have an effect. The investigators will be comparing this to a commonly used type of lithium, lithium carbonate. Investigators want to see if the crystalized lithium can have the same or better effect when compared to lithium carbonate. Past research has shown a greater effect within the body with crystalized lithium when compared to commonly used lithium. This past research suggests that crystallized lithium 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. During these stays participants will receive lithium carbonate for one stay and the crystalized lithium for the other. There are frequent blood draws and brain MRI scans during two periods of the study to look at how the crystalized lithium 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.
Interventions
DRUGAL001
Crystalized Lithium
Lithium Carbonate
Sponsors
Alzamend Neuro, Inc.
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. 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. 2. 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. 3. Able to understand and follow instructions during the study as determined by the Investigator. 4. Willing to follow study procedures. 5. Willing and able to adhere to study restrictions and to be confined at the clinical research center per protocol requirements. 6. Any gender, race, or ethnicity. 7. Able to understand and provide written informed consent. 8. 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). 9. 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: 1. 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). 2. 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. 3. 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). 10. Able to communicate in English, including speaking, reading, and writing. 11. Body mass index (BMI) within 18.0 to 30.0 kg/m2, inclusive, and body weight of at least 50 kg at the time of Screening. 12. ECG recording, after at least 5 minutes of rest in a supine position without clinically significant abnormalities as determined by the Investigator.
Exclusion criteria
1. 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. 2. Presence or history of any disorder that may prevent the successful completion of the study. 3. 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. 4. History of seizure disorder and/or severe head trauma (other than a single childhood febrile seizure). 5. History or presence of gastrointestinal disease including chronic gastritis, peptic ulcers, inflammatory bowel disease, hemorrhagic gastritis, or duodenitis. 6. History or presence of acute or chronic liver disease as determined by the Investigator. 7. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study treatments. 8. Any history of frequent headache or migraine. 9. Kidney disease (eGFR \<60 mL/minute/1.73 m2). 10. Uncontrolled tachy/brady arrhythmias, atrial fibrillation, or coronary heart failure. 11. 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. Uncontrolled hypertension with a sustained blood pressure \>160/100 mmHg at Screening, or at check-in on Day -1 (P1). 4. 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). 12. Psychiatric or neurological illnesses (e.g., depression, schizophrenia or other psychotic syndromes, Parkinson's disease and related movement disorders, seizure disorder, and myasthenia gravis). 13. Treatment with haloperidol, antipsychotics, monoamine oxidase inhibitors, neuromuscular blocking agents. Subjects who have ever received immunosuppressant treatment (excluding topical or oral corticosteroids taken 1 and 5 years before Screening, respectively). 14. Current and during Lithium treatment hyponatremia, defined as serum sodium laboratory value outside the standard reference range. 15. The use of any medication on a chronic basis with the exception of hormonal contraceptives for females of childbearing potential. An appropriate drug free period will be required for prescription or over the counter (OTC) drugs to washout, particularly of any especially long half-life drugs (see
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate differences in brain and/or brain structure lithium PK relative to plasma PK for AL001 capsule compared to a lithium carbonate capsule. | 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 | 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. | From enrollment to end of follow-up period at Day 42(P2) | Proportion of participants with adverse events and serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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 |
| Exploring Brain Pharmacodynamics using Magnetic Resonance Spectroscopy | From Screening (Day 1) to Day 23 (P2) | Magnetic resonance spectroscopy (MRS) techniques will be applied to explore brain metabolism, including possible metabolic similarities/differences between treatments |
Countries
United States
Outcome results
None listed