PMID- 22328206
OWN - NLM
STAT- MEDLINE
DCOM- 20130128
LR  - 20211021
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 14
IP  - 2
DP  - 2012 Jun
TI  - Population analyses of efficacy and safety of ABT-594 in subjects with diabetic 
      peripheral neuropathic pain.
PG  - 168-75
LID - 10.1208/s12248-012-9328-7 [doi]
AB  - ABT-594, a neuronal nicotinic acetylcholine receptor ligand, is 30- to 100-fold 
      more potent than morphine in animal models of nociceptive and neuropathic pain. 
      Efficacy and safety of ABT-594 in subjects with painful diabetic polyneuropathy 
      was evaluated in a phase 2 study. The objective of this work was to use a 
      nonlinear mixed effects model-based approach for characterizing the relationship 
      between dose and response (efficacy and safety) of ABT-594. Subjects (N = 266) 
      were randomized into four groups in a double-blind, placebo-controlled, 7-week 
      study to receive twice daily regimens of placebo or 150, 225, and 300 mug of 
      ABT-594. The primary efficacy variable, pain score (11-point Likert scale), was 
      assessed on five occasions. The probability of change from baseline pain score of 
      >/=1, >/=2, and >/=3 was modeled using cumulative logistic regression with dose and 
      days of treatment as explanatory variables. The incidence of five most frequently 
      occurring adverse events (AEs) was modeled using linear logistic regression. 
      ABT-594 ED(50) values (improvement in 50% of subjects) for improvement in pain 
      scores of >/=1, >/=2, and >/=3 were 50, 215, and 340 mug, respectively, for the average 
      number of days (33) on treatment. The rank order of ED(50) values for AEs was 
      nausea, vomiting, dizziness, headache, and abnormal dreams; nicotine users were 
      less sensitive to AEs. Population pharmacodynamic models developed to 
      characterize the improvement in pain score and incidence of adverse events 
      indicate an approximately twofold separation between the ED(50) values for 
      efficacy and AEs.
FAU - Dutta, Sandeep
AU  - Dutta S
AD  - Clinical Pharmacokinetics & Pharmacodynamics, Abbott, Dept. R4PK, Bldg. AP13A, 
      100 Abbott Park Road, Abbott Park, Illinois 60064-6104, USA. 
      sandeep.dutta@abbott.com
FAU - Hosmane, Balakrishna S
AU  - Hosmane BS
FAU - Awni, Walid M
AU  - Awni WM
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120211
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (5-(2-azetidinylmethoxy)-2-chloropyridine)
RN  - 0 (Azetidines)
RN  - 0 (Pyridines)
SB  - IM
MH  - Aged
MH  - Azetidines/adverse effects/*therapeutic use
MH  - Diabetes Mellitus/drug therapy/epidemiology
MH  - Diabetic Neuropathies/*drug therapy/epidemiology
MH  - Dizziness/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Headache/chemically induced
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neuralgia/*drug therapy/epidemiology
MH  - *Nonlinear Dynamics
MH  - Pyridines/adverse effects/*therapeutic use
MH  - Treatment Outcome
PMC - PMC3326158
EDAT- 2012/02/14 06:00
MHDA- 2013/01/29 06:00
PMCR- 2013/02/11
CRDT- 2012/02/14 06:00
PHST- 2011/10/05 00:00 [received]
PHST- 2012/01/31 00:00 [accepted]
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2013/01/29 06:00 [medline]
PHST- 2013/02/11 00:00 [pmc-release]
AID - 9328 [pii]
AID - 10.1208/s12248-012-9328-7 [doi]
PST - ppublish
SO  - AAPS J. 2012 Jun;14(2):168-75. doi: 10.1208/s12248-012-9328-7. Epub 2012 Feb 11.