Single Dose Study of ALZ-801 Prototype Tablets

Study Overview
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Brief Summary
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Phase 1, single-center, open-label, non-randomized, sequential single dose 4-period study in 12 healthy subjects to assess the pharmacokinetics of ALZ-801, tramiprosate and the primary metabolite of tramiprosate, NRM5074, from prototype drug product formulations of ALZ-801, and to assess effect of food on the bioavailability of ALZ-801 and tramiprosate of the prototype tablet formulation.

Detailed Description
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This is a single-center, open-label, non-randomized, sequential, single-dose, 4-period study in 12 healthy adult subjects. Subjects are to receive a single oral dose of ALZ-801 in each of the 4 study periods (Regimens A, B, C and D) in a non-randomized, sequential manner, separated by a minimum washout period of 7 days. The washout period is expected to last approximately 14 days to permit interim decisions to take place and to allow for the selection of the formulation of the subsequent regimen. Periods of interim analysis will take place following dosing with prototype formulations Regimens A, B, and C, during which the PK and safety data are reviewed to determine the dose to be administered in the subsequent treatment period. Interim decisions aim to identify a prototype ALZ-801 immediate release tablet formulation that provides a similar tramiprosate AUC and Cmax to that of historical values after administration of a 100 mg loose-filled tramiprosate capsule in the fasted state. Optimization of the required tramiprosate exposure will be made by adjusting the dose of ALZ-801 in the prototype tablets using a formulation design space with a target dose range, per tablet, of 171 to 514 mg ALZ-801 (equivalent to 100 mg to 300 mg tramiprosate). Dose selection will be made after a complete review of all data collected from the previous dose group. For dose selection to occur, data is required to be available from a minimum of 8 evaluable subjects with complete safety assessments up to 24 h post-dose, and required safety and PK data (AEs, plasma concentrations of ALZ-801, tramiprosate and NRM5074, and Tmax, Cmax and AUC estimates for ALZ-801 and tramiprosate).

Official Title
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Four-Period, Single-Dose, Sequential Study in Healthy Adults, to Assess Pharmacokinetics of ALZ-801 and Tramiprosate From ALZ-801 Prototype Tablets and Effect of Food on Bioavailability of ALZ-801 and Tramiprosate for Selected Prototype Tablet

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: ALZ-801 170 mg Fasting
* Drug: ALZ-801 205 mg Fasting
* Drug: ALZ-801 205 mg After Food
* Drug: ALZ-801 342 mg Fasting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females Females must be of non-childbearing potential Body mass index (BMI) of 18.0 to 35.0 kg/m2 Exclusion Criteria: History of any drug or alcohol abuse in the past 2 years Subjects known to have a creatinine clearance of <60 mL/min Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results History of cardiovascular, renal, hepatic, neurological, psychiatric, chronic respiratory or gastrointestinal disease as judged by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects were to receive a single oral dose of ALZ-801 in each of the 4 study periods (Regimens A, B, C and D) in a non-randomized, sequential manner, separated by a minimum washout period of 7 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A<br>ALZ-801 171 mg tablet, fasting, once | Drug: ALZ-801 170 mg Fasting<br> <br> |
| Experimental: Regimen B<br>ALZ-801 205 mg tablet, fasting, once | Drug: ALZ-801 205 mg Fasting<br> <br> |
| Experimental: Regimen C<br>ALZ-801 205 mg tablet, after food once | Drug: ALZ-801 205 mg After Food<br> <br> |
| Experimental: Regimen D<br>ALZ-801 342 mg (administered as 2 x 171 mg tablets of ALZ-801), after food, once | Drug: ALZ-801 342 mg Fasting<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for ALZ-801, tramiprosate, and NRM5074 | Maximum observed concentration | 72 hours after dosing | 
| Tmax for ALZ-801, tramiprosate, and NRM5074 | Time from dosing at which Cmax was apparent | 72 hours after dosing | 
| AUC for ALZ-801, tramiprosate, and NRM5074 | Area under the curve from time zero to the last measurable concentration | 72 hours after dosing | 
| T1/2 for ALZ-801, tramiprosate, and NRM5074 | The apparent elimination half-lifee | 72 hours after dosing | 
| Frel for ALZ-801 and tramiprosate | Relative bioavailability of mean PK parameters (AUC[0-inf] and Cmax) for fasted compared to fed state for ALZ-801 and tramiprosate | 72 hours after dosing | 
| Frel (test to literature reference) | Relative bioavailability of mean PK parameters (AUC[0-inf] and Cmax) for tramiprosate from ALZ-801 prototype tablet formulation compared to previous tramiprosate Phase 3 data | 72 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Incidence and nature of adverse events (AEs) and serious adverse events (SAEs). Assessments reported as AEs or SAEs include physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings | 72 hours |