Single Dose Study of ALZ-801 Prototype Tablets

Alzheon

Status and phase: Completed; Phase 1

Conditions: Alzheimer Disease

Treatments: Drug: ALZ-801 342 mg Fasting; Drug: ALZ-801 170 mg Fasting; Drug: ALZ-801 205 mg Fasting; Drug: ALZ-801 205 mg After Food

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04585347

ALZ-801-104

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 12 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 4 patient groups

Regimen A

Experimental group

Description:

ALZ-801 171 mg tablet, fasting, once

Treatment:

Drug: ALZ-801 170 mg Fasting

Regimen B

Experimental group

Description:

ALZ-801 205 mg tablet, fasting, once

Treatment:

Drug: ALZ-801 205 mg Fasting

Regimen C

Experimental group

Description:

ALZ-801 205 mg tablet, after food once

Treatment:

Drug: ALZ-801 205 mg After Food

Regimen D

Experimental group

Description:

ALZ-801 342 mg (administered as 2 x 171 mg tablets of ALZ-801), after food, once

Treatment:

Drug: ALZ-801 342 mg Fasting