Single Dose Study of ALZ-801 Prototype Tablets
- Conditions
- Alzheimer Disease
- Interventions
- Drug: ALZ-801 205 mg After FoodDrug: ALZ-801 170 mg FastingDrug: ALZ-801 205 mg FastingDrug: ALZ-801 342 mg Fasting
- Registration Number
- NCT04585347
- Lead Sponsor
- Alzheon Inc.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- Healthy males and females
- Females must be of non-childbearing potential
- Body mass index (BMI) of 18.0 to 35.0 kg/m2
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Regimen C ALZ-801 205 mg After Food ALZ-801 205 mg tablet, after food once Regimen A ALZ-801 170 mg Fasting ALZ-801 171 mg tablet, fasting, once Regimen B ALZ-801 205 mg Fasting ALZ-801 205 mg tablet, fasting, once Regimen D ALZ-801 342 mg Fasting ALZ-801 342 mg (administered as 2 x 171 mg tablets of ALZ-801), after food, once
- Primary Outcome Measures
Name Time Method AUC for ALZ-801, tramiprosate, and NRM5074 72 hours after dosing Area under the curve from time zero to the last measurable concentration
T1/2 for ALZ-801, tramiprosate, and NRM5074 72 hours after dosing The apparent elimination half-lifee
Frel (test to literature reference) 72 hours after dosing 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
Tmax for ALZ-801, tramiprosate, and NRM5074 72 hours after dosing Time from dosing at which Cmax was apparent
Cmax for ALZ-801, tramiprosate, and NRM5074 72 hours after dosing Maximum observed concentration
Frel for ALZ-801 and tramiprosate 72 hours after dosing Relative bioavailability of mean PK parameters (AUC\[0-inf\] and Cmax) for fasted compared to fed state for ALZ-801 and tramiprosate
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events 72 hours 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