Alzheimer's Disease, Healthy Non-elderly and Elderly Adults
Conditions
Brief summary
This is a Phase 1/2a, multi-center, placebo-controlled, double-blinded, randomized, multiple ascending dose (MAD) clinical trial to determine the safety and maximum tolerated dose of AL001. Up to 72 participants will be randomly assigned to receive study drug (active AL001) or placebo. The study consists of a 4-week screening period, a 14-day treatment period, and a 42-day follow-up period.
Detailed description
This is a Phase 1/2a, multi-center, placebo-controlled, double-blind, randomized, multiple ascending dose (MAD) clinical trial to determine the safety and maximum tolerated dose (MTD) of AL001, a crystal engineered lithium-salicylate-proline lithium delivery product that in nonclinical studies was shown to enhance and prolong the pharmacokinetic (PK) profile of lithium in the brain with enhanced efficacy potential in Alzheimer's models compared to lithium carbonate. A maximum of approximately 72 participants will be enrolled. Participants will be randomly assigned to receive study drug (active AL001) or placebo in a ratio of 6:2, respectively, with 8 patients in each dosing cohort. Placebos will be pooled and regarded as a comparative cohort for safety. Cohorts 2a, 3a, 4a and 5a will involve 1:1 healthy non-elderly and elderly subjects; cohorts 1, 2b, 3b, 4b and 5b will involve Alzheimer's subjects. The study will consist of a screening period (Days -28 to -2), a 14-day treatment period, and a 42-day follow-up period.
Interventions
DRUGAL001
a crystal engineered lithium-salicylate-proline lithium delivery product
OTHERPlacebo
matching placebo formulation
Sponsors
Alzamend Neuro, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double-blind
Intervention model description
Multi-center, placebo-controlled, double-blind, randomized, multiple ascending dose clinical trial to determine the safety and maximum tolerated dose of AL001.
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
(Alzheimer's Patients): * Mild to moderate Alzheimer's disease (reasonably good physical health per Investigator's review of medical & surgical history, physical examination incl. neurological examination, 12-lead ECG, vital signs, and clinical laboratory tests) * Able to understand and provide written informed consent and able to understand and follow instructions during study as determined by Investigator * Subject and caregiver (if accompanying subject on site) willing to follow study procedures, willing & able to adhere to study restrictions and to be confined at the clinical research center for 16 days * Fluent in English speaking, reading, and writing (for cognitive testing) * Availability of medical history to provide information about the cognitive and functional level of the participant and of a qualified source such as the caregiver willing and able to provide information about the cognitive and functional level of the participant * Males (non-vasectomized and vasectomized) must agree to use barrier contraception during the study until after Study Day 42 * Females must meet criteria if childbearing for contraception or be non-childbearing * Clinical diagnosis of dementia (neurocognitive disorder) by a qualified clinician based on the DSM-V criteria * Considered AD Stage 2, 3, or 4 based on the FDA classification * Mini-Mental State Examination (MMSE) score between 16 and 26, inclusive, at Screening * Negative result to COVID-19 test at Screening and admission (performed on Day -1)
Exclusion criteria
(Alzheimer's Patients): * Clinically significant abnormalities (as determined by investigator based on medical history, physical examination, vital sign measurements, ECG findings, or clinical laboratory findings) that may affect subject safety or successful study participation * Presence or history of any disorder 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 judgment of the Investigator, would make the subject inappropriate for entry into this study * 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 participant of the subject * Any history or presence of gastrointestinal disease including chronic gastritis, hemorrhagic gastritis, peptic ulcers, duodenitis, diarrhea, or inflammatory bowel disease * Any presence or history of acute or chronic liver diseases * Any post-surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study treatment * 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 * Psychiatric or neurological illnesses (other than Alzheimer's disease), e.g., schizophrenia or other psychotic syndromes, Parkinson's disease and related movement disorders, myasthenia gravis, and seizure disorder/history of seizure disorder and/or severe head trauma (other than a single childhood febrile seizure) * Presence of depression, except for mild depression with no acute episodes and stable condition, as determined by the Investigator * History of untreated thyroid dysfunction that may be independently associated with cognitive impairment * Central nervous system-related exclusions: 1. any medical condition that (per investigator's judgement) would affect subject safety and scientific integrity of the study, e.g., untreated hypothyroidism (TSH \>10 mIU/L) or vitamin B12 deficiency (\<300 pg/mL) which may contribute to cognitive impairment, delirium, non-AD dementia and other encephalopathies 2. Hachinski scale score \>4 or evidence of stroke within the past 5 years * 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, and HCV (unless quantitative PCR negative for HCV) at Screening 3. Uncontrolled hypertension with a sustained blood pressure \>160/100 mmHg at Screening, check-in (Day -1), and prior to the first study drug administration 4. Fever (body temperature \>101.4°F \[38.5°C\]), acute upper respiratory, or any other infections at Screening, check-in (Day -1), and prior to the first study drug administration * Any history of drug hypersensitivity, asthma (with the exception of childhood asthma), urticaria or other severe allergic diathesis * History of adverse - or hypersensitivity reaction to lithium, aspirin, salicylate, L-proline, or any test article excipient * Female who is breastfeeding, pregnant according to the pregnancy test at Screening or prior to the first study drug administration, or planning to become pregnant during the study * Magnetic resonance imaging (MRI)-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | 42 days with a 14-day treatment period | To evaluate the safety and tolerability of AL001 in healthy subjects and patients with adverse event(s), AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: Proportion of participants with treatment-emergent adverse events (TEAEs) * Proportion of participants with serious AEs * Proportion of participants with TEAEs that lead to premature discontinuation * Proportion of participants with abnormal values for each safety laboratory test (change from baseline) * Proportion of participants with abnormal values for each Electrocardiogram (ECG) parameter (change from baseline in standard 12-lead ECG parameters) For all analyses, placebo-treated subjects from each Cohort were combined (pooled) to provide a composite placebo group for all comparisons. Adverse event profiles for all treated subjects were benign as were placebo-treated subjects. No further statistical analyses were therefore appropriate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 42 days with a 14-day treatment period | To characterize the MTD of AL001 in all subjects treated with AL001: • Proportion of subjects in each Cohort with plasma trough measurements of lithium \> 1.0 mEq/L. Subjects above these values invoke stopping rules for subsequent cohort enrollment. |
| Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 42 days with a 14-day treatment period | To characterize the MTD of AL001 in all subjects: • Proportion of all subjects with plasma maximum concentration (Cmax) measurements for salicylate \> 30 mg/dL |
Countries
Canada, United States
Participant flow
Pre-assignment details
There were no pre-specified comparisons between healthy controls and AD patients.
Participants by arm
| Arm | Count |
|---|---|
| Multiple Ascending Doses of AL001- Cohort 1 (1890 mg AL001/d, 630mg TID ×14 Days) AD-only participants (no normal healthy subjects) were randomized to receive AL001. When adequate safety data were available, a review was done for all participants to make a dose-escalation or dose and/or regimen modification decision. This was repeated for each cohort.
A total of 8 cohorts received 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits.
Cohort 1 included 6 AD subjects only (7 were randomized because 1 subject voluntarily withdrew before dosing); 6 active AD subjects (as per randomization code) received the following treatment:
• Cohort 1: 60% of 450 mg lithium carbonate equivalent of AL001 (1890 mg AL001 daily ×14 days, given as 3 × 210 mg AL001 capsules TID)
AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 7 |
| Multiple Ascending Doses of AL001 - Cohort 2a (3150 mg AL001/d, 1050mg TID × 14 Days) The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated.
Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 2b (6 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort:
• Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID).
AL001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 6 |
| Multiple Ascending Doses of AL001 - Cohort 2b (3150 mg AL001/d, 1050mg TID × 14 Days) The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated.
Cohort 2 was divided into 2 sub-cohorts: Cohort 2a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 2b (8 AD subjects). Blinded results from Cohort 2a were reviewed by the safety review committee before Cohort 2b was randomized. Per randomization, there were 6 active subjects in each cohort:
• Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID).
AL001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 6 |
| Multiple Ascending Doses of AL001 - Cohort 3a (4410 mg AL001/d, 1470mg TID × 14 Days) The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated.
Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 3b (6 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort:
• Cohort 3a: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID)
AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 6 |
| Multiple Ascending Doses of AL001 - Cohort 3b (4410 mg AL001/d, 1470mg TID × 14 Days) The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated.
Cohort 3 was divided into 2 sub-cohorts: Cohort 3a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 3b (6 AD subjects). Blinded results from Cohort 3a were reviewed by the safety review committee before Cohort 3b was randomized. Per randomization, there were 6 active subjects in each cohort:
• Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID)
AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 6 |
| Multiple Ascending Doses of AL001 - Cohort 4a (5040 mg AL001/d, 1680mg TID × 14 Days) The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated.
Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 4b (6 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort:
• Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID)
AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 6 |
| Multiple Ascending Doses of AL001 - Cohort 4b (5040 mg AL001/d, 1680mg TID × 14 Days) The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated.
Cohort 4 was divided into 2 sub-cohorts: Cohort 4a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 4b (6 AD subjects). Blinded results from Cohort 4a were reviewed by the safety review committee before Cohort 4b was randomized. Per randomization, there were 6 active subjects in each cohort:
• Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID)
AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 6 |
| Multiple Ascending Doses of AL001 - Cohort 5a (6300 mg AL001/d, 2100mg TID × 14 Days) The data from the previous cohort were deemed safe before the next sequential cohort was enrolled and dosing initiated.
Cohort 5 was planned to be divided into 2 sub-cohorts: Cohort 5a (6 healthy subjects - 3 non-elderly adults and 3 elderly adults) and Cohort 5b (6 AD subjects).
Per randomization, there were 6 active normal healthy subjects in cohort 5a. Stopping rules were invoked by the Safety Committee due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations.
• Cohort 5a: 200% of 450 mg lithium carbonate equivalent of AL001 (6300 mg AL001 daily × 14 days - lithium dose equivalent to that used for bipolar/affective disorders, given as 10 × 210 mg AL001 capsules TID)
AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 6 |
| Multiple Ascending Doses of AL001 - Cohort 5b (6300 mg AL001/d, 2100mg TID × 14 Days) Subjects for Cohort 5b (6 AD subjects) were not enrolled because the Safety Committee invoked study stopping rules due to the pharmacokinetic results of Cohort 5a. The Stopping Rules were not invoked due to any adverse event. The stopping criteria were modest increases in plasma levels of lithium and salicylate above what is reported in the literature as the maximum therapeutic range concentrations.
• Cohort 5b was not dosed. Subjects would have been dosed at 200% of 450 mg lithium carbonate equivalent of AL001 (6300 mg AL001 daily × 14 days - lithium dose equivalent to that used for bipolar/affective disorders, given as 10 × 210 mg AL001 capsules TID)
AL 001: a crystal engineered lithium-salicylate-proline lithium delivery product. | 0 |
| Combined Placebo Group 2 subjects were randomized to receive matching placebo (no active drug) concurrently with each of the 8 treatment cohorts. A total of 16 subjects receiving placebo were combined in 1 group. | 16 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Multiple Ascending Doses of AL001- Cohort 1 (1890 mg AL001/d, 630mg TID ×14 Days) | Total | Combined Placebo Group | Multiple Ascending Doses of AL001 - Cohort 5a (6300 mg AL001/d, 2100mg TID × 14 Days) | Multiple Ascending Doses of AL001 - Cohort 4b (5040 mg AL001/d, 1680mg TID × 14 Days) | Multiple Ascending Doses of AL001 - Cohort 4a (5040 mg AL001/d, 1680mg TID × 14 Days) | Multiple Ascending Doses of AL001 - Cohort 3b (4410 mg AL001/d, 1470mg TID × 14 Days) | Multiple Ascending Doses of AL001 - Cohort 3a (4410 mg AL001/d, 1470mg TID × 14 Days) | Multiple Ascending Doses of AL001 - Cohort 2b (3150 mg AL001/d, 1050mg TID × 14 Days) | Multiple Ascending Doses of AL001 - Cohort 2a (3150 mg AL001/d, 1050mg TID × 14 Days) |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | 63.1 years | 60.2 years | 59.4 years | 57.3 years | 58.8 years | 58.8 years | 57.5 years | 57.5 years | 65.4 years | 65.4 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 28 Participants | 7 Participants | 0 Participants | 5 Participants | 0 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 37 Participants | 9 Participants | 6 Participants | 1 Participants | 6 Participants | 2 Participants | 4 Participants | 2 Participants | 6 Participants |
| Ratio of Plasma Lithium trough >1.0mEq/L or plasma salicylate peak concentrations >30mg/dL | 0 ratio | 0 ratio | 0 ratio | 0 ratio | 0 ratio | 0 ratio | 0 ratio | 0 ratio | 0 ratio | 0 ratio |
| Sex: Female, Male Female | 0 Participants | 34 Participants | 12 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 31 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 5 / 6 | 5 / 6 | 3 / 6 | 5 / 6 | 3 / 6 | 5 / 6 | 4 / 8 | 5 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings.
To evaluate the safety and tolerability of AL001 in healthy subjects and patients with adverse event(s), AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: Proportion of participants with treatment-emergent adverse events (TEAEs) * Proportion of participants with serious AEs * Proportion of participants with TEAEs that lead to premature discontinuation * Proportion of participants with abnormal values for each safety laboratory test (change from baseline) * Proportion of participants with abnormal values for each Electrocardiogram (ECG) parameter (change from baseline in standard 12-lead ECG parameters) For all analyses, placebo-treated subjects from each Cohort were combined (pooled) to provide a composite placebo group for all comparisons. Adverse event profiles for all treated subjects were benign as were placebo-treated subjects. No further statistical analyses were therefore appropriate.
Time frame: 42 days with a 14-day treatment period
Population: All subjects in the Randomized Analysis Set who received any dose of the study drug. This analysis set was used for all safety analyses.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 6 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 6 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 6 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 1 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 5 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 6 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 1 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 5 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 6 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 6 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 - Pooled Placebo Group | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Abnormal values for safety laboratory tests (change from baseline) | 0 Participants |
| Multiple Ascending Doses of AL001 - Pooled Placebo Group | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | TEAEs that lead to premature discontinuation | 0 Participants |
| Multiple Ascending Doses of AL001 - Pooled Placebo Group | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | Serious AEs | 0 Participants |
| Multiple Ascending Doses of AL001 - Pooled Placebo Group | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | No Adverse Events observed | 16 Participants |
| Multiple Ascending Doses of AL001 - Pooled Placebo Group | Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings. | abnormal ECG parameters (change from baseline) | 0 Participants |
Secondary
Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001
To characterize the MTD of AL001 in all subjects treated with AL001: • Proportion of subjects in each Cohort with plasma trough measurements of lithium \> 1.0 mEq/L. Subjects above these values invoke stopping rules for subsequent cohort enrollment.
Time frame: 42 days with a 14-day treatment period
Population: All subjects in the Safety Analysis Set who received AL001 and had a trough measurement for lithium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0.167 Proportion of Subjects |
| Multiple Ascending Doses of AL001 - Pooled Placebo Group | Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001 | 0 Proportion of Subjects |
Secondary
Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects
To characterize the MTD of AL001 in all subjects: • Proportion of all subjects with plasma maximum concentration (Cmax) measurements for salicylate \> 30 mg/dL
Time frame: 42 days with a 14-day treatment period
Population: All subjects in the Safety Analysis Set who received AL001 and had a Cmax measurement for salicylate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1 | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2a | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 2b | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0.167 Proportion of Subjects |
| Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b | Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects | 0 Proportion of Subjects |