Alzheimer Disease
Conditions
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).
Interventions
DRUGALZ-801 170 mg Fasting
DRUGALZ-801 205 mg Fasting
DRUGALZ-801 205 mg After Food
DRUGALZ-801 342 mg Fasting
Sponsors
Quotient Clinical
Alzheon Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC for ALZ-801, tramiprosate, and NRM5074 | 72 hours after dosing | Area under the curve from time zero to the last measurable concentration |
| Cmax for ALZ-801, tramiprosate, and NRM5074 | 72 hours after dosing | Maximum observed concentration |
| Tmax for ALZ-801, tramiprosate, and NRM5074 | 72 hours after dosing | Time from dosing at which Cmax was apparent |
| 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 |
| T1/2 for ALZ-801, tramiprosate, and NRM5074 | 72 hours after dosing | The apparent elimination half-lifee |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Outcome results
None listed