Clinical trial NCT04585347: Single Dose Study of ALZ-801 Prototype Tablets
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Alzheon Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quotient Clinical
First posted: 2020-10-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Cmax for ALZ-801, tramiprosate, and NRM5074
timeFrame: 72 hours after dosing
measure: Tmax for ALZ-801, tramiprosate, and NRM5074
timeFrame: 72 hours after dosing
measure: AUC for ALZ-801, tramiprosate, and NRM5074
timeFrame: 72 hours after dosing
measure: T1/2 for ALZ-801, tramiprosate, and NRM5074
timeFrame: 72 hours after dosing
measure: Frel for ALZ-801 and tramiprosate
timeFrame: 72 hours after dosing
measure: Frel (test to literature reference)
timeFrame: 72 hours after dosing
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: 72 hours
Other outcomes:
Locations:
Study officials:
affiliation: Quotient Clinical
name: Ann Church, PhD
role: STUDY_DIRECTOR
References:
citation: Hey JA, Yu JY, Versavel M, Abushakra S, Kocis P, Power A, Kaplan PL, Amedio J, Tolar M. Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease. Clin Pharmacokinet. 2018 Mar;57(3):315-333. doi: 10.1007/s40262-017-0608-3.