PMID- 26683109
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20220408
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Linking)
VI  - 157
IP  - 1
DP  - 2016 Jan
TI  - A randomized, phase 2 study investigating TRV130, a biased ligand of the mu-opioid 
      receptor, for the intravenous treatment of acute pain.
PG  - 264-272
LID - 10.1097/j.pain.0000000000000363 [doi]
AB  - Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 
      is a structurally novel biased ligand of the mu-opioid receptor that activates G 
      protein signaling with little beta-arrestin recruitment. In this phase 2, 
      randomized, placebo- and active-controlled study, we investigated the efficacy 
      and tolerability of TRV130 in acute pain after bunionectomy. We used an adaptive 
      study design in which 144 patients experiencing moderate-to-severe acute pain 
      after bunionectomy were randomized to receive double-blind TRV130, placebo, or 
      morphine in a pilot phase. After pilot phase analysis, 195 patients were 
      randomized to receive double-dummy TRV130 0.5, 1, 2, or 3 mg every 3 hours (q3h); 
      placebo; or morphine 4 mg q4h intravenously. The primary end point was the 
      time-weighted average change in numeric rating scale pain intensity over the 
      48-hour treatment period. Secondary end points included stopwatch and categorical 
      assessments of pain relief. Safety and tolerability were also assessed. TRV130 2 
      and 3 mg q3h, and morphine 4 mg q4h produced statistically greater mean 
      reductions in pain intensity than placebo over 48 hours (P < 0.005). TRV130 at 2 
      and 3 mg produced significantly greater categorical pain relief than morphine (P 
      < 0.005) after the first dose, with meaningful pain relief occurring in under 5 
      minutes. TRV130 produced no serious AEs, with tolerability similar to morphine. 
      These results demonstrate that TRV130 rapidly produces profound analgesia in 
      moderate-to-severe acute pain, suggesting that G-protein-biased mu-opioid receptor 
      activation is a promising target for development of novel analgesics.
FAU - Viscusi, Eugene R
AU  - Viscusi ER
AD  - Thomas Jefferson University, Philadelphia, PA, USA PRA Health Sciences, Salt Lake 
      City, UT, USA Premier Research Group Ltd, Austin, TX, USA Cytel Inc, 
      Chesterbrook, PA, USA Trevena, Inc, King of Prussia, PA, USA.
FAU - Webster, Lynn
AU  - Webster L
FAU - Kuss, Michael
AU  - Kuss M
FAU - Daniels, Stephen
AU  - Daniels S
FAU - Bolognese, James A
AU  - Bolognese JA
FAU - Zuckerman, Seth
AU  - Zuckerman S
FAU - Soergel, David G
AU  - Soergel DG
FAU - Subach, Ruth Ann
AU  - Subach RA
FAU - Cook, Emily
AU  - Cook E
FAU - Skobieranda, Franck
AU  - Skobieranda F
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 
      (((3-methoxythiophen-2-yl)methyl)((2-(9-(pyridin-2-yl)-6-oxaspiro(4.5)decan-9-yl)ethyl))amine)
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Receptors, Opioid, mu)
RN  - 0 (Spiro Compounds)
RN  - 0 (Thiophenes)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Acute Pain/*drug therapy/etiology
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Analgesics, Opioid/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Hallux Valgus/surgery
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Morphine/therapeutic use
MH  - Orthopedic Procedures/adverse effects
MH  - Receptors, Opioid, mu/*agonists
MH  - Spiro Compounds/*therapeutic use
MH  - Thiophenes/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2015/12/20 06:00
MHDA- 2016/10/07 06:00
CRDT- 2015/12/20 06:00
PHST- 2015/12/20 06:00 [entrez]
PHST- 2015/12/20 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
AID - 00006396-201601000-00027 [pii]
AID - 10.1097/j.pain.0000000000000363 [doi]
PST - ppublish
SO  - Pain. 2016 Jan;157(1):264-272. doi: 10.1097/j.pain.0000000000000363.