PMID- 27046445
OWN - NLM
STAT- MEDLINE
DCOM- 20171124
LR  - 20181113
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Print)
IS  - 1080-7683 (Linking)
VI  - 32
IP  - 8
DP  - 2016 Oct
TI  - A Randomized Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and 
      Pharmacokinetics of Trabodenoson in Healthy Adult Volunteers.
PG  - 548-554
AB  - PURPOSE: To investigate the safety, tolerability, and pharmacokinetics of 
      trabodenoson, a highly selective adenosine mimetic targeting the adenosine A(1) 
      receptor. METHODS: In Part 1, 60 healthy adult volunteers were randomized to 14 
      days of twice-daily topical monocular application of placebo or trabodenoson 
      (200, 400, 800, 1,600, 2,400, or 3,200 mug). In Part 2, 10 subjects were 
      randomized to placebo or 8 escalating doses of bilateral trabodenoson (total 
      daily doses: 1,800-6,400 mug). RESULTS: The incidence of treatment-related adverse 
      events in Part 1 was similar in the trabodenoson (27.8%) and placebo (25.0%) 
      groups. Most were mild in intensity. The most common adverse events (AEs) for 
      trabodenoson and placebo were headache (25.0% vs. 33%, respectively) and eye pain 
      (11.1% vs. 4.2%, respectively). Ocular AEs were infrequent (16.7% and 17.9%, 
      respectively), were self-limited, lasted <24 h, and were typically mild in 
      intensity. The most common ocular AE was eye pain (9.5% and 3.6%, respectively), 
      with a single observation of ocular hyperemia (200 mug trabodenoson). Trabodenoson 
      was rapidly absorbed [median time to maximum concentration (t(max)):  approximately 0.08 to 
      0.27 h] and eliminated (t((1/2)): 0.48-2.0 h), with no evidence of drug accumulation. 
      Systemic exposure to topical trabodenoson was dose related but not dose 
      proportional, with a plateau effect at doses >/=2,400 mg per eye. No clinically 
      significant treatment-related systemic AEs were observed, and increasing systemic 
      exposure had no effect on heart rate or blood pressure. CONCLUSIONS: Ocular doses 
      of trabodenoson up to 3,200 mug per eye were safe and well tolerated in the eye 
      and resulted in no detectable systemic effects in healthy adult volunteers.
FAU - Laties, Alan
AU  - Laties A
AD  - 1 Scheie Eye Institute , Philadelphia, Pennsylvania.
FAU - Rich, Cadmus C
AU  - Rich CC
AD  - 2 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
FAU - Stoltz, Randall
AU  - Stoltz R
AD  - 3 Covance Global Clinical Pharmacology , Evansville, Indiana.
FAU - Humbert, Vernon
AU  - Humbert V
AD  - 4 Evansville Heart Center , Evansville, Indiana.
FAU - Brickman, Chaim
AU  - Brickman C
AD  - 2 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
FAU - McVicar, William
AU  - McVicar W
AD  - 2 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
FAU - Baumgartner, Rudolf A
AU  - Baumgartner RA
AD  - 2 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160405
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
SB  - IM
MH  - Adult
MH  - Aged
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Eye/physiopathology
MH  - *Healthy Volunteers
MH  - Humans
MH  - Middle Aged
MH  - Ocular Hypertension/chemically induced
PMC - PMC5069726
OTO - NOTNLM
OT  - Trabodenoson
OT  - adenosine
OT  - intraocular pressure
OT  - ocular hypertension
OT  - primary open angle glaucoma
OT  - trabecular meshwork
COIS- Author Disclosure Statement A.L. is a consultant and member of the Inotek 
      Scientific Advisory Board. C.C.R., C.B., W.M., and R.A.B. are or were employees 
      of Inotek Pharmaceuticals during the conduct of the work reported herein and own 
      stock and stock options. R.S. and V.H have no competing financial interests.
EDAT- 2016/10/19 06:00
MHDA- 2017/11/29 06:00
PMCR- 2016/10/01
CRDT- 2016/04/06 06:00
PHST- 2016/10/19 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2016/04/06 06:00 [entrez]
PHST- 2016/10/01 00:00 [pmc-release]
AID - 10.1089/jop.2015.0147 [pii]
AID - 10.1089/jop.2015.0147 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2016 Oct;32(8):548-554. doi: 10.1089/jop.2015.0147. Epub 
      2016 Apr 5.