Safety and Pharmacokinetics of ALZ-507 in Healthy Elderly Adults

This is a Phase 1, single-center, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of ALZ-507 following single ascending doses (SAD) and multiple ascending doses (MAD) in healthy adult participants aged 50 to 75 years.

ALZ-507 is an investigational oral formulation. The study will evaluate the safety profile of ALZ-507 and characterize its pharmacokinetic properties in plasma, urine, and cerebrospinal fluid (CSF).

The study consists of two parts:

Part 1: Single Ascending Dose (SAD)

Part 1 will evaluate the safety, tolerability, and plasma and urine pharmacokinetics of single ascending oral doses of ALZ-507 in healthy participants. Up to 60 participants will be enrolled into sequential dose cohorts and randomized in a 3:1 ratio to receive ALZ-507 or matching placebo.

Planned dose levels include 150 mg, 350 mg, 550 mg, 750 mg, and an optional 950 mg dose level. Dose escalation decisions will be based on review of available safety, tolerability, and pharmacokinetic data by a Safety Review Committee (SRC). One cohort will participate in a food-effect evaluation in which the same treatment is administered under both fasted and fed conditions following an adequate washout period.

Participants will undergo screening assessments to determine eligibility before admission to the clinical research unit. Following administration of study drug, serial blood and urine samples will be collected to characterize the pharmacokinetics of ALZ-507. Safety evaluations will include monitoring of adverse events, clinical laboratory testing, vital signs, physical examinations, and electrocardiograms (ECGs).

Part 2: Multiple Ascending Dose (MAD)

Part 2 will evaluate the safety, tolerability, and pharmacokinetics of multiple ascending doses of ALZ-507 administered once daily for 14 days. Approximately 24 participants will be enrolled into two sequential cohorts and randomized in a 3:1 ratio to receive ALZ-507 or matching placebo.

Dose levels for Part 2 are planned to be selected based on the safety and pharmacokinetic results from Part 1. Participants will receive study treatment once daily for 14 consecutive days. Pharmacokinetic assessments will be conducted in plasma, cerebrospinal fluid and urine.

A single CSF sample will be collected on Day 14 to assess penetration of ALZ-507 into the central nervous system. For participants assigned to placebo, a sham lumbar puncture procedure will be performed to maintain study blinding.

Safety Assessments

Safety and tolerability will be assessed throughout the study by evaluation of:

Adverse events and serious adverse events Clinical laboratory parameters, including hematology, clinical chemistry, and urinalysis Vital signs Physical examinations 12-lead electrocardiograms

Pharmacokinetic Assessments

Pharmacokinetic analyses will be performed using plasma, urine, and CSF samples collected at predefined time points. Assessments will characterize absorption, distribution, metabolism, and elimination of ALZ-507 following single and multiple dosing. The effect of food on pharmacokinetics will also be evaluated in Part 1. Multiple-dose assessments will evaluate steady-state pharmacokinetics and accumulation following repeated administration.

Participants will attend a follow-up visit approximately 10 to 17 days after their last dose for ongoing safety assessment and study completion.

The results of this study will provide information regarding the safety, tolerability, pharmacokinetic profile, food effect, and CSF exposure of ALZ-507 and will support dose selection and future clinical development of the investigational product.

Inclusion criteria

• Healthy males and females aged 50 to 75 years, inclusive
• Body mass index 18.0 to 35.0 kg/m2, inclusive, and >50 kg body weight
• No clinically significant values for vital signs (systolic blood pressure [BP] 90 to 140 mmHg, diastolic BP 40 to 90 mmHg, and HR 50 to 100 bpm) and no clinically significant ECG readings, as determined by the principal investigator or sub investigator

Exclusion criteria

• Participation in a clinical research study within the previous 30 days or within a period of less than 5 times the drug's half-life
• Have previously participated in a trial with ALZ-801 or tramiprosate and received study drug
• History of any drug or alcohol abuse in the past 2 years
• Creatinine clearance of <60 mL/min using the Cockcroft-Gault equation at screening
• Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the investigator
• History of clinically significant cardiovascular, pulmonary, chronic respiratory, renal, hepatic, GI, immunologic, endocrine, neurologic, psychiatric or thromboembolic disease; a history of metabolic disturbances; or any current physical conditions that could interfere with the interpretation of the study results as judged by the investigator