MON-319 COMPARISON OF PHARMACOKINETIC PARAMETERS OF DESIDUSTAT IN PRE-DIALYSIS CHRONIC KIDNEY DISEASE INDIAN PATIENTS AND AUSTRALIAN HEALTHY VOLUNTEERS

Abstract

Anemia is a condition of decrease in red blood cells (RBCs) or/and hemoglobin, which can be caused by a range of serious medical conditions, like chronic kidney disease (CKD), chemotherapy induced anemia (CIA), anemia of chronic disease (ACD) etc. 27-42% of Desidustat (previously ZYAN1) is eliminated by kidney. The aim of this retrospective analysis was to compare pharmacokinetic (PK) parameters in pre-dialysis CKD Indian patients and Australian healthy volunteers post single dose administration. Retrospective analyses were conducted on phase I and phase II studies with Desidustat: a study of healthy Australian volunteers (study A) and pre-dialysis CKD Indian patients (study B). In study A, healthy Australian males received Desidustat (10 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg) or placebo under fasted conditions. In study B, pre-dialysis CKD Indian patients received a single Desidustat (100 mg, 150 mg and 200 mg) or placebo under fasted conditions. PK analysis of Desidustat was conducted as part of these original studies. The calculated PK parameters were maximum plasma concentration (Cmax), time for Cmax (Tmax), area under plasma concentration from time zero to last measurable concentration (AUC0-t), area under plasma concentration from time zero to time infinity (AUC0-inf), elimination rate constant (kel) and terminal-phase half-life (t1/2). PK data for healthy Australian males aged 18–65 years, with a body weight of >55 kg, BMI within range of 18-30 kg/m2 and receiving Desidustat 100 mg (n=6), 150 mg (n=6) and 200 mg (n=6) in study A were compared with PK data for pre-dialysis CKD Indian patients aged 18–65 years, with a body weight of ≥45 kg and receiving Desidustat 100 mg (n=11), 150 mg (n=11) and 200 mg (n=11) in study B. Single-dose PK parameters under fasted conditions across both studies are shown in the table. The PK data across all these studies indicate that the clearance of Desidustat is lower in the pre-dialysis CKD patients than in Australian healthy individuals. Compared with healthy volunteers, pre-dialysis CKD patients had >1.5-fold increase in Cmax and >2.4‑fold increase in AUC0-t for 100 mg, 150 mg and 200 mg strengths. No serious AEs were observed during either study.