PMID- 29484638
OWN - NLM
STAT- MEDLINE
DCOM- 20190708
LR  - 20191210
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 103
IP  - 6
DP  - 2018 Jun
TI  - Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Volunteers Treated With 
      GDC-0853, a Selective Reversible Bruton's Tyrosine Kinase Inhibitor.
PG  - 1020-1028
LID - 10.1002/cpt.1056 [doi]
AB  - GDC-0853 is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) that is 
      highly selective and noncovalent, leading to reversible binding. In double-blind, 
      randomized, and placebo-controlled phase I healthy volunteer studies, GDC-0853 
      was well tolerated, with no dose-limiting adverse events (AEs) or serious AEs. 
      The maximum tolerated dose was not reached during dose escalation (</=600 mg, 
      single ascending dose (SAD) study; </=250 mg twice daily (b.i.d.) and </=500 mg once 
      daily, 14-day multiple ascending dose (MAD) study). Plasma concentrations peaked 
      1-3 hours after oral administration and declined thereafter, with a steady-state 
      half-life ranging from 4.2-9.9 hours. Independent assays demonstrated 
      dose-dependent BTK target engagement. Based on pharmacokinetic/pharmacodynamic 
      (PK/PD) simulations, a once-daily dosing regimen (e.g., 100 mg, q.d.) is expected 
      to maintain a high level of BTK inhibition over the dosing interval. Taken 
      together, the safety and PK/PD data support GDC-0853 evaluation in rheumatoid 
      arthritis, lupus, and other autoimmune or inflammatory indications.
CI  - (c) 2018 American Society for Clinical Pharmacology and Therapeutics.
FAU - Herman, Ann E
AU  - Herman AE
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Chinn, Leslie W
AU  - Chinn LW
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Kotwal, Shweta G
AU  - Kotwal SG
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Murray, Elaine R
AU  - Murray ER
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Zhao, Rui
AU  - Zhao R
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Florero, Marilyn
AU  - Florero M
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Lin, Alyse
AU  - Lin A
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Moein, Anita
AU  - Moein A
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Wang, Rena
AU  - Wang R
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Bremer, Meire
AU  - Bremer M
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Kokubu, Serika
AU  - Kokubu S
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Serone, Adrian P
AU  - Serone AP
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Hanze, Eva L
AU  - Hanze EL
AD  - qPharmetra, Stockholm, Sweden.
FAU - Viberg, Anders
AU  - Viberg A
AD  - qPharmetra, Stockholm, Sweden.
FAU - Morimoto, Alyssa M
AU  - Morimoto AM
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Winter, Helen R
AU  - Winter HR
AD  - Genentech, Inc, South San Francisco, California, USA.
FAU - Katsumoto, Tamiko R
AU  - Katsumoto TR
AD  - Genentech, Inc, South San Francisco, California, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180323
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridones)
RN  - E9L2885WUL (fenebrutinib)
RN  - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Agammaglobulinaemia Tyrosine Kinase/*antagonists & inhibitors
MH  - Area Under Curve
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Piperazines/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Protein Kinase Inhibitors/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Pyridones/administration & dosage/adverse effects/pharmacokinetics/*pharmacology
MH  - Young Adult
EDAT- 2018/02/28 06:00
MHDA- 2019/07/10 06:00
CRDT- 2018/02/28 06:00
PHST- 2018/01/17 00:00 [received]
PHST- 2018/02/09 00:00 [revised]
PHST- 2018/02/12 00:00 [accepted]
PHST- 2018/02/28 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
PHST- 2018/02/28 06:00 [entrez]
AID - 10.1002/cpt.1056 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2018 Jun;103(6):1020-1028. doi: 10.1002/cpt.1056. Epub 2018 
      Mar 23.