PMID- 32274653
OWN - NLM
STAT- MEDLINE
DCOM- 20200909
LR  - 20221207
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Print)
IS  - 1173-2563 (Linking)
VI  - 40
IP  - 5
DP  - 2020 May
TI  - Pharmacokinetics, Pharmacodynamics, and Safety of Peficitinib (ASP015K) in 
      Healthy Male Caucasian and Japanese Subjects.
PG  - 469-484
LID - 10.1007/s40261-020-00910-w [doi]
AB  - BACKGROUND AND OBJECTIVE: Peficitinib pharmacokinetics and pharmacodynamics have 
      been characterized mainly in Caucasian subjects. This study investigated the 
      pharmacokinetics, pharmacodynamics, safety, and tolerability of peficitinib in 
      healthy Japanese subjects compared with Caucasian subjects. METHODS: In this 
      single-center, randomized, double-blind, placebo-controlled study, a cohort of 
      healthy Japanese (n = 24) and Caucasian (n = 24) men received a single oral dose 
      of peficitinib (20, 60, or 200 mg) or placebo. Another cohort of Japanese men 
      (n = 24) received peficitinib (10, 30, or 100 mg) or placebo twice daily for 
      7 days. Pharmacokinetic and pharmacodynamic parameters were assessed, and adverse 
      events (AEs) monitored throughout. RESULTS: Dose proportionality of maximum 
      plasma drug concentration (C(max)) and area under the plasma concentration-time 
      curve extrapolated to infinity (AUC(inf)) was demonstrated for both ethnicities. 
      The geometric mean ratio for dose-normalized C(max) was 45.7-98.8% higher and 
      AUC(inf) was 33.8-66.4% higher in Japanese versus Caucasian subjects. Mean peak 
      inhibition of STAT5 phosphorylation was higher in Japanese than Caucasian 
      subjects for a given peficitinib dose, but inhibition was comparable across 
      ethnicities for a given plasma peficitinib concentration. In the multiple-dose 
      study, plasma peficitinib concentrations were similar on day 1 and day 7. All AEs 
      were mild, and none resulted in study discontinuation. CONCLUSIONS: Peficitinib 
      was well tolerated at doses up to 200 mg daily for 7 days in healthy Japanese 
      subjects. Dose-proportional exposure was demonstrated across the single-dose 
      range of 20-200 mg, with greater peficitinib exposure in Japanese compared with 
      Caucasian subjects. The pharmacokinetic/pharmacodynamic relationships were 
      considered comparable between these populations. CLINICALTRIALS. GOV IDENTIFIER: 
      NCT01225224.
FAU - Shibata, Mai
AU  - Shibata M
AUID- ORCID: 0000-0001-5370-662X
AD  - Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan. 
      mai.shibata@astellas.com.
FAU - Hatta, Toshifumi
AU  - Hatta T
AD  - Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan.
FAU - Saito, Masako
AU  - Saito M
AD  - Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan.
FAU - Toyoshima, Junko
AU  - Toyoshima J
AD  - Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan.
FAU - Kaneko, Yuichiro
AU  - Kaneko Y
AD  - Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan.
FAU - Oda, Kazuo
AU  - Oda K
AD  - Astellas Research Institute of America LLC, 1 Astellas Way, Northbrook, IL, 
      60062, USA.
FAU - Nishimura, Tetsuya
AU  - Nishimura T
AD  - Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT01225224
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Placebos)
RN  - 25X51I8RD4 (Niacinamide)
RN  - HPH1166CKX (peficitinib)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/adverse effects/*analogs & derivatives/pharmacokinetics/pharmacology
MH  - Adult
MH  - Area Under Curve
MH  - *Asian People
MH  - Double-Blind Method
MH  - Health Status
MH  - Healthy Volunteers
MH  - Humans
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Niacinamide/adverse effects/*analogs & derivatives/pharmacokinetics/pharmacology
MH  - Placebos
MH  - *White People
MH  - Young Adult
PMC - PMC7181426
COIS- M. Shibata, T. Hatta, M. Saito, J. Toyoshima, Y. Kaneko, and T. Nishimura are 
      employees of Astellas Pharma Inc. K. Oda is an employee of Astellas Research 
      Institute of America LLC.
EDAT- 2020/04/11 06:00
MHDA- 2020/09/10 06:00
PMCR- 2020/04/09
CRDT- 2020/04/11 06:00
PHST- 2020/04/11 06:00 [pubmed]
PHST- 2020/09/10 06:00 [medline]
PHST- 2020/04/11 06:00 [entrez]
PHST- 2020/04/09 00:00 [pmc-release]
AID - 10.1007/s40261-020-00910-w [pii]
AID - 910 [pii]
AID - 10.1007/s40261-020-00910-w [doi]
PST - ppublish
SO  - Clin Drug Investig. 2020 May;40(5):469-484. doi: 10.1007/s40261-020-00910-w.