Pharmacokinetics, Safety, and Pharmacodynamics of Romiplostim in Chinese Subjects With Immune Thrombocytopenia: A Phase I/II Trial

Abstract

Romiplostim is approved for the treatment of immune thrombocytopenia (ITP). This study aimed to evaluate the pharmacokinetics, safety, and pharmacodynamics of romiplostim in Chinese patients with ITP. This multicenter, open-label, dose-escalation phase I/II trial enrolled ITP patients from 5 centers in China between October 2015 and August 2017. There were 2 cohorts: 1 μg/kg and 3 μg/kg weekly for 2 weeks. The end points included pharmacokinetics, platelet changes from baseline, hematological indicators, and adverse events (AEs). Sixteen participants, with 8 patients in each cohort, were enrolled. In the 1 μg/kg cohort, time to maximum concentration was 4.00 (4.00-7.83) hours, maximum serum drug concentration was 52.0 (16.0-228.0) pg/mL, and area under the serum drug concentration-time curve from time 0 to the last detectable time point was 389 (32.0-5400) pg · h/mL. In the 3 μg/kg cohort, time to maximum serum drug concentration was 11.91 (4.00-12.00) hours, maximum serum drug concentration was 105.0 (25.5-313.0) pg/mL, and half-life was 12.7 (8.2-23.6) hours. The absolute change of peak platelet count from baseline was 14 (3-40) and 72 (3-369) ×10⁹ /L in the 1 and 3 μg/kg cohorts, respectively. Seven (87.5%) and eight (100%) participants had treatment-emergent AEs in 1 μg/kg cohort and 3 μg/kg cohort, respectively. No major AEs occurred in the 2 cohorts. Romiplostim (1 and 3 μg/kg) is safe and well tolerated in Chinese patients with ITP.

Trial registration: ClinicalTrials.gov NCT02868060.

Keywords: immune thrombocytopenia; pharmacodynamics; pharmacokinetics; phase I/II; romiplostim; safety.

Figure 1

Pharmacokinetics of romiplostim. Mean serum romiplostim concentration (pg/mL), linear plot. The error bars are standard deviations.

Figure 2

Pharmacodynamics of romiplostim. Mean platelet count‐time profiles (linear plot). The error bars are standard deviations.