Background: Idiopathic thrombocytopenic purpura (ITP) especially refractory and (or) relapsed ITP, is a serious and global health burden and its clinical treatment is far from being satisfied. Hetrombopag is a novel, small-molecule thrombopoietin receptor agonist for the treatment of chronic idiopathic thrombocytopenic purpura (CITP).
Objectives: This first-in-patient study aimed to investigate the safety, pharmacokinetics, and anticipated therapeutic dose of hetrombopag in CITP patients.
Methods: In this multicenter, first-in-patient study, CITP patients received hetrombopag in a dose escalation (2.5 mg/day, 5 mg/day, or 7.5 mg/day) cohort. All patients received hetrombopag in fasting condition once daily for 2 weeks.
Results: Of 44 patients screened, 32 were enrolled and treated. Most adverse events were graded 1 to 2 (ie, mild to moderate), and the incidence and severity were similar for three study cohorts. The pharmacokinetics of hetrombopag were found to be nonlinear with greater than dose-proportional: 12.5% of patients (1/8) in the 2.5 mg/d cohort, 58.3% of patients (7/12) in the 5 mg/d cohort, 66.7% of patients (8/12) in the 7.5 mg/d cohort reached the primary study endpoint of a platelet count exceeding 50 × 109 /L on day 28.
Conclusion: Hetrombopag was well tolerated and preliminarily efficacious. Efficacy, safety, and pharmacokinetic data suggest that 7.5 mg hetrombopag once daily was the anticipated therapeutic dose of hetrombopag in CITP patients and has been recommended for investigation in a later confirmatory clinical study of hetrombopag.
Trial registration: ClinicalTrials.gov NCT02403440.
Keywords: anticipated therapeutic dose; first-in-patient; hetrombopag; idiopathic thrombocytopenic purpura; pharmacokinetics.
© 2020 International Society on Thrombosis and Haemostasis.