PMID- 34921514
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220722
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 11
IP  - 3
DP  - 2022 Mar
TI  - Pharmacokinetics, Safety, and Pharmacodynamics of Romiplostim in Chinese Subjects 
      With Immune Thrombocytopenia: A Phase I/II Trial.
PG  - 379-387
LID - 10.1002/cpdd.1059 [doi]
AB  - 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 mug/kg and 3 mug/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 mug/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 mug/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) x10(9) 
      /L in the 1 and 3 mug/kg cohorts, respectively. Seven (87.5%) and eight (100%) 
      participants had treatment-emergent AEs in 1 mug/kg cohort and 3 mug/kg cohort, 
      respectively. No major AEs occurred in the 2 cohorts. Romiplostim (1 and 3 mug/kg) 
      is safe and well tolerated in Chinese patients with ITP.
CI  - (c) 2021 The Authors. Clinical Pharmacology in Drug Development published by Wiley 
      Periodicals LLC on behalf of American College of Clinical Pharmacology.
FAU - Qi, Junyuan
AU  - Qi J
AD  - Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical 
      Sciences & Peking Union Medical College, Beijing, China.
FAU - Zheng, Li
AU  - Zheng L
AD  - West China Hospital of Sichuan University, Chengdu, China.
FAU - Hu, Bei
AU  - Hu B
AD  - Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 
      Beijing, China.
FAU - Zhou, Hu
AU  - Zhou H
AD  - Henan Cancer Hospital/The Affiliated Cancer Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - He, Qing
AU  - He Q
AD  - Wuxi People's Hospital, Wuxi, China.
FAU - Liu, Hong
AU  - Liu H
AD  - Kyowa Kirin China Pharmaceutical Co., Ltd., Shanghai, China.
FAU - Kawai, Hironori
AU  - Kawai H
AD  - Kyowa Kirin Co., Ltd, Tokyo, Japan.
FAU - Yang, Renchi
AU  - Yang R
AD  - National Clinical Research Center for Blood Diseases, State Key Laboratory of 
      Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, 
      Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 
      China.
LA  - eng
SI  - ClinicalTrials.gov/NCT02868060
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20211217
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Receptors, Fc)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9014-42-0 (Thrombopoietin)
RN  - GN5XU2DXKV (romiplostim)
SB  - IM
MH  - Humans
MH  - *Purpura, Thrombocytopenic, Idiopathic/chemically induced/drug therapy
MH  - Receptors, Fc/therapeutic use
MH  - Recombinant Fusion Proteins
MH  - Thrombopoietin/adverse effects
MH  - Treatment Outcome
PMC - PMC9299913
OTO - NOTNLM
OT  - immune thrombocytopenia
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - phase I/II
OT  - romiplostim
OT  - safety
COIS- All authors declare that they have no competing interests.
EDAT- 2021/12/19 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/07/20
CRDT- 2021/12/18 06:21
PHST- 2021/06/24 00:00 [received]
PHST- 2021/11/21 00:00 [accepted]
PHST- 2021/12/19 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2021/12/18 06:21 [entrez]
PHST- 2022/07/20 00:00 [pmc-release]
AID - CPDD1059 [pii]
AID - 10.1002/cpdd.1059 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2022 Mar;11(3):379-387. doi: 10.1002/cpdd.1059. Epub 
      2021 Dec 17.