Objective: This phase I study of ZYAN1 was conducted to evaluate the safety, tolerability, and pharmacokinetics following oral administration in healthy volunteers.
Study Design: A randomised, double-blind, placebo-controlled phase I study carried out in two parts in addition to a third part involving an open-label study to evaluate the food/sex effect.
Dosing: Part I: Single-dose study with ZYAN1 10, 25, 50, 100, 150, 200, and 300 mg (n = 56)
Part II: Multiple-dose study with every other day dosing of ZYAN1 100, 150, 200, and 300 mg (n = 32)
Part III: Sex and food effect study with ZYAN1 150 mg (n = 12; open-label).
Result: Part I: Single-dose study with ZYAN1 10, 25, 50, 100, 150, 200, and 300 mg (n = 56)
Part II: Multiple-dose study with every other day dosing of ZYAN1 100, 150, 200, and 300 mg (n = 32)
Part III: Sex and food effect study with ZYAN1 150 mg (n = 12; open-label).
Regardless of single or multiple doses, mean Cmax and area under the concentration–time curve from time zero to time t (AUCt) values generally showed a dose-proportional increase. The mean elimination half-life (t) of ZYAN1 ranged from 6.9 to 13 h with negligible accumulation. Following a single dose of ZYAN1, the mean serum erythropoietin (EPO) Cmax values showed dose response (i.e., 6.6 and 79.9 mIU/L for 10 and 300 mg ZYAN1 doses, respectively), while the time to mean.18
Conclusion: Oral single (10–300 mg) and multiple dosing (100–300 mg) of ZYAN1 in healthy subjects was found to be safe and well-tolerated. With increasing ZYAN1 dose, there was almost a proportional increase in mean Cmax and AUCt. The mean serum EPO concentrations showed a trend of dose response. Based on the t, pharmacodynamics 566.47 ± 163.03 to 17,858.33 ± 2899.19 ng/mL and the activity, and lack of drug accumulation, a once every 2 days dosing regimen of ZYAN1 was appropriate for phase II study.18
*Desidustat's initial molecular name.
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