This is a first-in-human, Phase 1, single-center, randomized, single-blind, placebo-controlled, single dose-escalation study to evaluate the safety, tolerability, PK, PD of SSS17 following oral administration in healthy subjects. Approximately 65 subjects (53 receiving active drug and 12 receiving placebo) will participate in this study.
The study will enroll healthy volunteers from a single academic medical center in China. All participants will be informed about the study and potential risks and required to provide written informed consent prior to undergoing study-related procedures. The improved Fibonacci dose escalation design will be implemented. The protocol specifies 10 mg, oral, one time for the first cohort without placebo control. Successive cohorts will be given doses up to 540 mg with placebo parallel control. Only no observation meets the criteria under stop rules, dose will escalate to the next higher level. The study will be divided into 2 stages: 1st period (fast) and 2nd period(fed). First period (fast): Subjects will be allocated 1:4 to receive placebo or SSS17, which will be administered by oral route. At each dose, tolerability, safety, PK and PD characteristics will be investigated. Second period (fed): in order to investigate the effects of food on PK and PD of SSS17. Subjects in one cohort will be administered again after meal on Day15. The accurate dose will be adjusted according to the findings in 1st period (fast)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
65
Shanghai Public Health Clinical Center
Shanghai, Shanghai Municipality, China
AEs
assessment AEs by frequency, severity
Time frame: up to Day14 or 29
Maximum plasma concentration (Cmax) of SSS17
Plasma samples will be collected and Cmax will be assessed.
Time frame: [ up to 48 hours post-dose]
Area under the concentration-time curve (AUC) of plasma concentration of SSS17
Plasma samples will be collected and the AUC from zero to infinity will be assessed.
Time frame: [ up to 48 hours post-dose]
Time-to-Cmax (Tmax) of SSS 17
Plasma samples will be collected and the Tmax will be assessed from the concentration-time curve.
Time frame: [ up to 48 hours post-dose]
Elimination terminal half-life (t1/2) of SSS17
Plasma samples will be collected and the t1/2 will be assessed.
Time frame: [up to 48 hours post-dose]
Total amount of SSS17 excreted in urine over 24 hours (Ae0-24)
Urine sample will be collected at pre-specified intervals and Ae0-24 will be assessed.
Time frame: only for one cohort (up to 72 hours post-dose)
Fraction of SSS17 excretion during each collection interval (Fe0-24)
Urine sample will be collected at pre-specified intervals and Fe0-24 will be assessed.
Time frame: only for one cohort (up to 72 hours post-dose)
Total amount of SSS17 excreted in urine over 72 hours (Ae0-72)
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Urine sample will be collected at pre-specified intervals and Ae0-72 will be assessed.
Time frame: only for one cohort (up to 72 hours post-dose)
Fraction of SSS17 excretion during each collection interval (Fe0-72)
Urine sample will be collected at pre-specified intervals and Fe0-72 will be assessed.
Time frame: only for one cohort (up to 72 hours post-dose)
Renal clearance (CLR) of SSS17
Urine sample will be collected at pre-specified intervals and CLR will be assessed.
Time frame: only for one cohort (up to 72 hours post-dose)
EPO concentrations
Change of EPO concentrations from baseline following SSS17
Time frame: up to 168 hours post-dose.
VEGF concentrations
Change of VEGF concentrations from baseline following SSS17
Time frame: up to 168 hours post-dose.
Change of RTC from baseline
Change of RTC from baseline following SSS17
Time frame: up to 168 hours post-dose.
Change of RBC from baseline
Change of RBC from baseline following SSS17
Time frame: up to 168 hours post-dose.
Change of Hgb from baseline
Change of Hgb from baseline following SSS17
Time frame: up to 168 hours post-dose.
Change of hepcidin from baseline
Change of serum hepcidin concentrations from baseline following SSS17
Time frame: up to 168 hours post-dose.