Phase I Clinical Study of ZYAN1, A Novel Prolyl-Hydroxylase (PHD) Inhibitor to Evaluate the Safety, Tolerability, and Pharmacokinetics Following Oral Administration in Healthy Volunteers.

Objective: This phase I study of ZYAN1 was conducted to evaluate the safety, tolerability, and pharmacokinetics following oral administration in healthy volunteers.

Methods: The study was a randomized, 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. A total of 100 subjects were enrolled into the study as follows: 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); and part III-sex and food effect study with ZYAN1 150 mg (n = 12; open-label).

A sensitive assay for ZYAN1 in human whole blood and urine utilizing positive LC-MS/MS electrospray ionization.

Aim: A sensitive LC-MS/MS method was developed and validated for estimation of ZYAN1 in human blood/urine.

Methods: An analog internal standard IOX2 along with ZYAN1 was quantified using selective reaction monitoring in positive mode. The chromatographic separation was performed by gradient elution with C analytical column (3 µm, 50 mm × 2.