PMID- 27085586
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 38
IP  - 6
DP  - 2016 Jun
TI  - Safety, Pharmacokinetic, and Pharmacodynamic Evaluation After Single and Multiple 
      Ascending Doses of a Novel Selective Androgen Receptor Modulator in Healthy 
      Subjects.
PG  - 1401-1416
LID - S0149-2918(16)30162-X [pii]
LID - 10.1016/j.clinthera.2016.03.025 [doi]
AB  - PURPOSE: Tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) properties 
      of single ascending doses (SADs) and multiple ascending doses (MADs) of 
      PF-06260414, a novel selective androgen receptor modulator, were assessed after 
      oral administration in healthy subjects. METHODS: Range of SAD and MAD levels 
      tested were 1 to 400 mg and 3 to 100 mg BID, respectively (n = 8 per cohort). In 
      addition, a 60-mg once-daily (n = 8) cohort and a Japanese cohort receiving 30 mg 
      BID (n = 7) also received PF-06260414. Plasma was collected to study PK 
      properties and hypothalamic-pituitary-gonadal (HPG) axis hormones. Tolerability 
      was evaluated from adverse events (AEs), physical examinations, vital signs, 
      ECGs, and clinical laboratory results. FINDINGS: PF-06260414 was well tolerated 
      with no serious AEs. The most frequently reported AEs were increase in alanine 
      aminotransferase and headache, which were reported by 7 and 3 subjects, 
      respectively. PF-06260414 had fast absorption (median Tmax, approximately 1-2 
      hours), a mean t(1/2) of approximately 6.9 to 12.8 hours, time-independent PK 
      properties and dose proportionality. Cmax and AUCtau geometric means in Japanese 
      subjects were 98.6% and 79.5% higher than in Western subjects, respectively, but 
      had similar HPG axis modulation. Changes in HPG axis hormones monitored in SADs 
      were similar to placebo. Maximum placebo-corrected modulations were observed for 
      total testosterone and sex hormone-binding globulin in the MAD 100-mg BID 
      regimen. IMPLICATIONS: This study was the first to compare a number of different 
      factors of PF-06260414, including tolerability, PK and PD properties, and ethnic 
      differences between Japanese and Western healthy subjects. PF-06260414 had 
      favorable PK properties and found that sex hormone-binding globulin, total 
      testosterone, and HDL were most sensitive to modulation. ClinicalTrials.gov 
      identifier: NCT02070939.
CI  - Copyright (c) 2016 Elsevier HS Journals, Inc. All rights reserved.
FAU - Bhattacharya, Indranil
AU  - Bhattacharya I
AD  - Pfizer, Cambridge, Massachusetts. Electronic address: 
      neil.bhattacharya@pfizer.com.
FAU - Tarabar, Sanela
AU  - Tarabar S
AD  - Pfizer, New Haven, Connecticut.
FAU - Liang, Yali
AU  - Liang Y
AD  - Pfizer, Groton, Massachusetts.
FAU - Pradhan, Vivek
AU  - Pradhan V
AD  - Pfizer, Cambridge, Massachusetts.
FAU - Owens, Jane
AU  - Owens J
AD  - Pfizer, Cambridge, Massachusetts.
FAU - Oemar, Barry
AU  - Oemar B
AD  - Pfizer, Cambridge, Massachusetts.
LA  - eng
SI  - ClinicalTrials.gov/NCT02070939
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160413
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (AR protein, human)
RN  - 0 (Androgens)
RN  - 0 (Isoquinolines)
RN  - 0 (PF-06260414)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Black or African American
MH  - Androgens/*administration & dosage/adverse effects/pharmacokinetics/pharmacology
MH  - Area Under Curve
MH  - Asian
MH  - Double-Blind Method
MH  - Headache/chemically induced
MH  - Humans
MH  - Isoquinolines/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Receptors, Androgen/*metabolism
MH  - White People
MH  - Young Adult
OTO - NOTNLM
OT  - *first in human
OT  - *hypothalamic-pituitary-gonadal axis hormones
OT  - *pharmacodynamic properties
OT  - *pharmacokinetic properties
OT  - *selective androgen receptor modulator
EDAT- 2016/04/18 06:00
MHDA- 2017/09/19 06:00
CRDT- 2016/04/18 06:00
PHST- 2015/12/25 00:00 [received]
PHST- 2016/02/24 00:00 [revised]
PHST- 2016/03/15 00:00 [accepted]
PHST- 2016/04/18 06:00 [entrez]
PHST- 2016/04/18 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
AID - S0149-2918(16)30162-X [pii]
AID - 10.1016/j.clinthera.2016.03.025 [doi]
PST - ppublish
SO  - Clin Ther. 2016 Jun;38(6):1401-1416. doi: 10.1016/j.clinthera.2016.03.025. Epub 
      2016 Apr 13.