Evaluation of the effect of lanthanum carbonate hydrate on the pharmacokinetics of roxadustat in non-elderly healthy adult male subjects.

What is known and objectiveRoxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor currently being investigated for the treatment of anemia in chronic kidney disease. Lanthanum carbonate is a phosphate binder that is commonly used to treat hyperphosphatemia in patients with chronic kidney disease. This study investigated the effect of lanthanum carbonate on the pharmacokinetics, safety and tolerability of a single oral dose of roxadustat in healthy non-elderly adult male subjects. MethodsThis was an open-label, randomized, two-period, two-sequence crossover study in non-elderly healthy adult males. Subjects randomized to Group 1 received roxadustat alone during Period 1 and roxadustat concomitantly with lanthanum carbonate during Period 2; subjects randomized to Group 2 received roxadustat concomitantly with lanthanum carbonate during Period 1 and roxadustat alone during Period 2. All subjects received a single oral dose of 100mg roxadustat on Day 1 in both periods. Subjects receiving concomitant lanthanum carbonate received 750mg lanthanum carbonate three times daily on Days 1 and 2. Pharmacokinetic assessments were conducted on Days 1-4 in both periods. The primary study outcomes were the area under the concentration-time curve from the time of dosing extrapolated to infinity (AUC(inf)), and maximum concentration (C-max); the geometric least squares mean ratio (GMR; roxadustat+lanthanum carbonate/roxadustat alone) and corresponding 90% confidence interval (CI) was calculated for AUC(inf) and C-max. Safety was assessed by the occurrence of treatment-emergent adverse events (TEAEs), laboratory test results, vital signs and standard 12-lead electrocardiogram. Results and discussionA total of 18 subjects were enrolled (Group 1, n=9; Group 2, n=9); no subjects discontinued from the study. Roxadustat was rapidly absorbed, reaching maximum plasma concentration between 1 and 4hours. The GMRs for AUC(inf) and C-max were 88.00% (90% CI: 84.01, 92.17) and 98.58% (90% CI: 92.92, 104.58), respectively. The 90% CIs for both parameters were within the no-effect boundaries of 80% and 125%, indicating a lack of effect of lanthanum carbonate on roxadustat absorption. No deaths or serious TEAEs occurred. What is new and conclusionsConcomitant administration of a single oral dose of 100mg roxadustat and 750mg lanthanum carbonate three times daily did not impact the AUC(inf) or C-max of roxadustat and was considered safe and well tolerated in non-elderly healthy adult male Japanese subjects.