The study will be conducted in 5 parts: Part A and Part B (single ascending dose \[SAD\] in solution formulation and tablet respectively), Part D and Part D2 (cold pressor test \[CPT\] to evaluate pain tolerance following single dose), and Part E (multiple ascending doses \[MAD\] in tablet formulation).
* Part A is a randomized, double-blind, placebo-controlled, SAD study to assess safety, tolerability, and pharmacokinetics (PK) of FZ008-145 solution in healthy subjects. Up to 32 subjects will be enrolled in 4 cohorts. * Part B is a randomized, double-blind, placebo-controlled, SAD study to assess safety, tolerability, and PK of FZ008-145 tablet in healthy subjects. Up to 72 subjects will be enrolled in 9 cohorts. * Part D is a randomized, double-blind, placebo-controlled, 3-period, 3-treatment, 6-sequence crossover study to evaluate the cold pain tolerance effect of FZ008-145 tablet in healthy subjects. A total of 12 healthy subjects will be randomized to receive each of the three treatments (FZ008-145 at two dose levels and placebo) across three treatment periods, with appropriate washout between periods. * Part D2 is a randomized, double-blind, placebo-controlled, 3-period, 3-treatment, 6-sequence crossover study to evaluate the cold pain tolerance effect of FZ008-145 tablet in healthy subjects. A total of 12 healthy subjects will be randomized to evaluates higher single oral doses (FZ008-145 at two dose levels and placebo) across three treatment periods, with appropriate washout between periods. * Part E is an open-label, multiple ascending dose (MAD) study to assess the safety, tolerability, and pharmacokinetics of FZ008-145 tablet in healthy subjects. Approximately 48 healthy subjects will be enrolled into 6 sequential cohorts receiving once-daily or twice daily oral doses of FZ008-145 for 14 consecutive days under fasted conditions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
176
Dose formulation- Oral solution
Dose formulation- Oral tablet
Dose formulation- Matching doses
CMAX Clinical Research Pty
Adelaide, South Australia, Australia
To assess the safety of FZ008-145 solution by number of adverse events (AEs) and treatment-emergent adverse events (TEAEs)
Safety of FZ008-145 solution is assessed by the incidence, nature, and severity of adverse events (AEs) and treatment-emergent adverse events (TEAEs) following administration of FZ008-145 solution. AEs and TEAEs are collected from the time of dosing through the end of the study and are summarized by number of participants experiencing at least one event.
Time frame: up to 14 days post first dose administration
To assess the safety of FZ008-145 tablet by number of adverse events (AEs) and treatment-emergent adverse events (TEAEs)
Safety of FZ008-145 solution is assessed by the incidence, nature, and severity of adverse events (AEs) and treatment-emergent adverse events (TEAEs) following administration of FZ008-145 solution. AEs and TEAEs are collected from the time of dosing through the end of the study and are summarized by number of participants experiencing at least one event.
Time frame: up to 14 days post first dose administration
Number of participants with changes in laboratory parameters determined as adverse events following oral dose of FZ008-145 solution and FZ008-145 tablet
The number of participants experiencing laboratory parameter abnormalities that are assessed as clinically significant and reported as adverse events (AEs) or treatment-emergent adverse events (TEAEs) following oral administration of FZ008-145 solution or FZ008-145 tablet.
Time frame: up to 14 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
Cmax- Maximum plasma concentration
Time frame: Up to 5 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
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Tmax- Time taken for maximum concentration
Time frame: Up to 5 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
AUC0-last- Area under curve from 0 to last
Time frame: Up to 5 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
AUC0-inf- Area under curve from 0 to infinity
Time frame: Up to 5 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
t1/2- terminal half-life
Time frame: Up to 5 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
CL/F- Apparent total body clearance
Time frame: Up to 5 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
Vz/F- Apparent total volume of distribution
Time frame: Up to 5 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
Ae- Amount of analyte that is eliminated in urine
Time frame: Up to 4 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
Fe- Fraction of analyte eliminated in Urine
Time frame: Up to 4 days post first dose administration
To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
CLr- Clearance rate
Time frame: Up to 4 days post first dose administration