A Single-Center, Randomized, Open-Label, Two-Formulation, Two-Sequence, Two-Period Crossover Study to Evaluate the Bioequivalence of Two Eltrombopag Olamine Tablets (25 mg) in Healthy Chinese Subjects in the Fed State.

BACKGROUND AND

objectiveEltrombopag is an orally active thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia. The purpose of this randomized study is to evaluate the bioequivalence of test and reference eltrombopag olamine tablets in healthy Chinese subjects after consuming a low-calcium, high-fat, high-calorie breakfast.

methodsThis was a single-center, randomized, open-label, two-sequence, two-period crossover study. Enrolled subjects were randomly divided into two groups at a 1:1 ratio, with each group randomly receiving either the test or reference eltrombopag olamine tablets per period. The washout period was set to 14 days. The concentration of eltrombopag in plasma was quantified using validated liquid chromatography-tandem mass spectrometry. Safety assessments were conducted throughout the entire trial.

resultsThis study ultimately included 36 healthy subjects. The geometric mean ratio for maximum plasma concentration between the test or reference eltrombopag olamine tablets was 92.68%; the geometric mean ratio for the area under the concentration-time curve from the time zero to the last measurable concentration was 97.15%; for the area under the concentration-time curve from the time zero to infinity, the geometric mean ratio was 97.30%. The geometric mean ratios and their 90% confidence intervals for the key pharmacokinetic parameters fell within the range of 80.00-125.00%. Within the safety data set of 36 subjects, adverse events were reported in nine subjects, totaling 14 occurrences. All reported adverse events were Grade 1, and no serious adverse events occurred.

conclusionsThese findings indicate that a single oral administration of the test eltrombopag is bioequivalent to the reference eltrombopag in healthy subjects after consuming a low-calcium, high-fat, high-calorie breakfast, with both formulations exhibiting a favorable safety profile. These results support the therapeutic interchangeability of the test formulation with the reference product, offering a reliable alternative for clinical use. CLINICAL

trial registrationThis trial was registered at the Drug Clinical Trial Registration and Information Disclosure Platform ( http://www.chinadrugtrials.org.cn , CTR20230598) and ClinicalTrials.gov ( https://clinicaltrials.gov , NCT06768619).