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Evaluation of the effect of lanthanum carbonate hydrate on the pharmacokinetics of roxadustat in non‐elderly healthy adult male subjects
Author(s) -
Shibata T.,
Nomura Y.,
Takada A.,
Aoki S.,
Katashima M.,
Murakami H.
Publication year - 2018
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12729
Subject(s) - lanthanum carbonate , pharmacokinetics , medicine , cmax , tolerability , lanthanum , crossover study , kidney disease , adverse effect , phosphate binder , pharmacology , gastroenterology , hyperphosphatemia , chemistry , placebo , inorganic chemistry , alternative medicine , pathology
Summary What is known and objective Roxadustat 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. Methods This 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 100 mg roxadustat on Day 1 in both periods. Subjects receiving concomitant lanthanum carbonate received 750 mg 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 ( TEAE s), laboratory test results, vital signs and standard 12‐lead electrocardiogram. Results and discussion A 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 4 hours. The GMR s 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% CI s 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 TEAE s occurred. What is new and conclusions Concomitant administration of a single oral dose of 100 mg roxadustat and 750 mg 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.