PMID- 30203841
OWN - NLM
STAT- MEDLINE
DCOM- 20190715
LR  - 20191210
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 183
IP  - 3
DP  - 2018 Nov
TI  - Avatrombopag, an oral thrombopoietin receptor agonist: results of two 
      double-blind, dose-rising, placebo-controlled Phase 1 studies.
PG  - 466-478
LID - 10.1111/bjh.15574 [doi]
AB  - Avatrombopag is an oral thrombopoietin receptor agonist that has been recently 
      approved for treating thrombocytopenia in chronic liver disease patients needing 
      invasive procedures. Clinical trials supporting this new treatment were guided by 
      two double-blind, dose-rising, placebo-controlled Phase 1 studies in healthy 
      adults reported here that assessed safety, tolerability and pharmacokinetic 
      profile of avatrombopag, and its effect on platelet counts. Subjects were 
      randomised (2:1) in the single-dose study (N = 63) to avatrombopag (1, 3, 10, 20, 
      50, 75 and 100 mg) or placebo, and in the multiple-dose study (N = 29) to 
      avatrombopag (3, 10 and 20 mg) or placebo daily for 14 days. There were no 
      serious adverse events (AEs), dose-limiting toxicities, deaths, AEs causing 
      withdrawal, thromboses or liver function abnormalities. In both studies, 
      avatrombopag peak concentration and exposure increased proportionally relative to 
      dose; half-life was 18-21 h and independent of dose, supporting once-daily 
      dosing. Effects on platelet counts depended on dose, concentration and treatment 
      duration. Platelet count increases began 3-5 days post-administration, with 
      maximum changes of >370 x 10(9) /l over baseline with 20 mg daily after 
      13-16 days. These data support continued development of avatrombopag for 
      treatment of other thrombocytopenic conditions and provide important guidance for 
      the haematologist in the use of this new thrombopoietin receptor agonist.
CI  - (c) 2018 The Authors. British Journal of Haematology published by John Wiley & Sons 
      Ltd and British Society for Haematology.
FAU - Kuter, David J
AU  - Kuter DJ
AUID- ORCID: 0000-0003-2084-8810
AD  - Center for Hematology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Allen, Lee F
AU  - Allen LF
AD  - Dova Pharmaceuticals, Durham, NC, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20180911
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Receptors, Thrombopoietin)
RN  - 0 (Thiazoles)
RN  - 0 (Thiophenes)
RN  - 3H8GSZ4SQL (avatrombopag)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptors, Thrombopoietin/*agonists
MH  - Thiazoles/*administration & dosage/adverse effects
MH  - Thiophenes/*administration & dosage/adverse effects
MH  - Thrombocytopenia/blood/*drug therapy
PMC - PMC6282597
OTO - NOTNLM
OT  - avatrombopag
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - platelets
OT  - thrombopoietin
EDAT- 2018/09/12 06:00
MHDA- 2019/07/16 06:00
PMCR- 2018/12/06
CRDT- 2018/09/12 06:00
PHST- 2018/04/20 00:00 [received]
PHST- 2018/07/09 00:00 [accepted]
PHST- 2018/09/12 06:00 [pubmed]
PHST- 2019/07/16 06:00 [medline]
PHST- 2018/09/12 06:00 [entrez]
PHST- 2018/12/06 00:00 [pmc-release]
AID - BJH15574 [pii]
AID - 10.1111/bjh.15574 [doi]
PST - ppublish
SO  - Br J Haematol. 2018 Nov;183(3):466-478. doi: 10.1111/bjh.15574. Epub 2018 Sep 11.