Single Dose Study of ALZ-801 Prototype Tablets

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: 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

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).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alzheon Inc.
• Collaborators: Quotient Clinical
• Investigators: Study Director: Ann Church, PhD, Quotient Clinical

Publications and helpful links

General Publications

• 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.

Helpful Links

• Clinical Pharmacokinetics and Safety of ALZ-801

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2015
• Primary Completion (Actual): November 13, 2015
• Study Completion (Actual): November 13, 2015

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 12, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: ALZ-801-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No