Evaluation of Food and Spherical Carbon Adsorbent Effects on the Pharmacokinetics of Roxadustat in Healthy Nonelderly Adult Male Japanese Subjects. Issue 3 (2nd July 2018)

• Record Type: Journal Article
• Authors: Shibata, Tomohisa; Nomura, Yuki; Takada, Akitsugu; Ueno, Mai; Katashima, Masataka; Yazawa, Rie; Furihata, Kenichi
• Is Part Of: Clinical pharmacology in drug development. Volume 8:Issue 3(2019)
• Page Start: 304
• Page End: 313
• Publication Date: 2018-07-02
• Subjects: drug‐drug interaction -- food‐drug interaction -- pharmacokinetics -- roxadustat -- spherical carbon adsorbent; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.597
• Languages: English
• ISSNs: 2160-7648

Abstract

Abstract: Roxadustat is a hypoxia‐inducible factor prolyl hydroxylase inhibitor in late‐stage clinical development for the treatment of anemia in chronic kidney disease. Spherical carbon adsorbent (SCA) is used in patients with chronic kidney disease and has been shown to impact absorption of certain concomitant drugs. Two phase 1, open‐label, randomized, crossover studies were conducted in healthy adult Japanese males to investigate the effect of food and SCA on the pharmacokinetics of a single oral dose of roxadustat. Subjects in the food effect study received a single dose of 100‐mg roxadustat under fed and fasted conditions. Subjects in the SCA/roxadustat drug‐drug interaction study received a single dose of 100‐mg roxadustat alone, concomitantly with SCA, and 1 and 2 hours before and after SCA to consider the real‐world clinical situation and assess any potential impact of a lag time on the pharmacokinetics of roxadustat. Primary outcomes for both studies were area under the concentration‐time curve from the time of dosing extrapolated to infinity and maximum concentration of drug in blood plasma. In the food effect study (N = 16), the geometric mean ratio (fed/fasted) and 90% confidence interval for area under the concentration‐time curve from the time of dosing extrapolated to infinity and maximum concentration of roxadustat were 94.44 (89.93‐99.18) and 79.88 (72.09‐88.52), respectively. In the SCA/roxadustat drug‐drug interaction study, all geometric mean ratios and 90% confidence intervals (roxadustat + SCA/roxadustat) were within the no‐effect boundaries of 80% and 125%. Roxadustat was generally well tolerated. The effect of food on the pharmacokinetics of roxadustat and the drug‐drug interaction between roxadustat and SCA do not appear to be clinically relevant and support the safe use of roxadustat under these conditions.