A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ABT-594 in patients with diabetic peripheral neuropathic pain

Pain. 2009 Dec;146(3):245-252. doi: 10.1016/j.pain.2009.06.013. Epub 2009 Jul 24.

Abstract

ABT-594 is a neuronal nicotinic acetylcholine receptor (NNR) agonist that exhibits potent analgesic activity in preclinical models of acute, chronic, and neuropathic pain. The purpose of this phase 2, randomized, multicenter, double-blind, placebo-controlled study was to evaluate the safety and analgesic efficacy of ABT-594 in patients with diabetic peripheral neuropathic pain (DPNP). A total of 266 DPNP patients were randomized 1:1:1:1 to receive placebo, ABT-594 150 microg BID, ABT-594 225 microg BID, or ABT-594 300 microg BID. Patients were titrated to a fixed-dose of ABT-594 over 7 days and remained at this dose for another 6 weeks. Compared to placebo, all three ABT-594 treatment groups showed significantly greater decreases on the average diary-based 0-10 Pain Rating Scale (PRS) score from baseline to final evaluation, the primary efficacy measure (placebo, -1.1; 150 microg BID, -1.9; 225 microg BID, -1.9; 300 microg BID, -2.0). The proportion of patients achieving at least a 50% improvement in the average diary-based PRS was greater in all three ABT-594 treatment groups. However, adverse event (AE) dropout rates were significantly higher in all three ABT-594 treatment groups (28% for 150 microg BID, 46% for 225 microg BID, and 66% for 300 microg BID) than for the placebo group (9%). Consistent with the expected side-effect profile of NNR agonists, the most frequently reported AEs were nausea, dizziness, vomiting, abnormal dreams, and asthenia. This study establishes proof of concept for NNR agonists as a new class of compounds for treating neuropathic pain.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analgesics, Non-Narcotic / therapeutic use*
  • Azetidines / adverse effects
  • Azetidines / pharmacokinetics
  • Azetidines / therapeutic use*
  • Data Interpretation, Statistical
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / pharmacokinetics
  • Nicotinic Agonists / therapeutic use*
  • Pain / drug therapy*
  • Pain / etiology
  • Pain Measurement / drug effects
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Socioeconomic Factors
  • Treatment Outcome

Substances

  • 5-(2-azetidinylmethoxy)-2-chloropyridine
  • Analgesics, Non-Narcotic
  • Azetidines
  • Nicotinic Agonists
  • Pyridines