A Food-Effect Study to Evaluate the Oral Bioavailability of Desidustat

This randomized, single-treatment, 2-sequence study evaluated the food effect on oral bioavailability of desidustat. Healthy adult male and female subjects were enrolled and randomly assigned to receive desidustat 50 mg orally in a fasting state in one period and a fed state in the other period. A standardized high-fat, high-calorie breakfast was served to assess the food effect. The pharmacokinetic results showed that the time to maximum blood concentration of desidustat was delayed significantly (P < .0001) in the fed state compared to the fasting state. The ingestion of food decreased the maximum blood concentration (C-max) compared to the fasting state (mean C-max, 3248 ng/mL in the fed state vs 5496 ng/mL in the fasting state). The geometric mean ratio of fed/fasting for log-normal (ln) C-max was 57. The exposure decreased in the fed state compared to the fasting state (mean area under the concentration-time curve [AUC] over the dosing interval, 25 559 ng center dot h/mL in the fed state versus 33 705 ng center dot h/mL in the fasting state; mean AUC from time 0 to infinity [AUC(0-infinity)], 25,910 ng center dot h/mL in the fed state vs 34 233 ng center dot h/mL in the fasting state). The geometric mean ratio of fed/fasting for lnAUC from time 0 to the last quantifiable concentration and ln AUC(0-)(infinity) was 77 and 76, respectively. The 90%CI of fed/fasting ratio of the geometric mean of lnC(max), AUC over the dosing interval, and AUC(0-infinity) of desidustat 50 mg did not fall within 80%-125% margin. Therefore, the absence of food effect could not be established. It can be inferred that food has a significant effect on the oral absorption of desidustat. Therefore, food must not be consumed 1 hour before and 2 hours after the oral administration of desidustat.