Efficacy and safety of the α 4β 2 neuronal nicotinic receptor agonist ABT-894 in patients with diabetic peripheral neuropathic pain

Michael C. Rowbotham, Armen Arslanian, Wolfram Nothaft, W. Rachel Duan, Andrea E. Best, Yili Pritchett, Qian Zhou, Brett R. Stacey

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Preclinical and clinical studies suggest that neuronal nicotinic receptor (NNR) agonists may be a novel and effective therapy for numerous painful conditions. Analgesic efficacy and safety of the highly selective α 4β 2 NNR agonist ABT-894 was evaluated in 2 separate randomized, double-blind, multicenter, placebo-controlled clinical trials in patients with diabetic peripheral neuropathic pain (DPNP). Study 1 (280 patients randomized) tested 1, 2, and 4 mg ABT-894 twice daily compared with placebo and 60 mg duloxetine once per day over 8 weeks of treatment. Study 2 (124 patients randomized) tested 6 mg ABT-894 twice daily vs placebo for 8 weeks. The primary efficacy outcome measure in both studies was the weekly mean of the 24-hour average pain score recorded in each patient's diary. In both trials, none of the ABT-894 dose groups showed efficacy compared with placebo, whereas duloxetine achieved a statistically significant improvement over placebo in Study 1. All dose levels of ABT-894 were well tolerated, and no significant safety issues were identified. These results are in contrast to the outcome of a previously reported study of DPNP using the less selective α 4β 2 NNR agonist ABT-594, which demonstrated efficacy compared with placebo, albeit with significant tolerability limitations. The failure of the highly selective α 4β 2 NNR agonist ABT-894 indicates that it may not be possible to define a therapeutic index for this mechanism or that selectively targeting α 4β 2 NNRs may not be a viable approach to treating neuropathic pain.

Original languageEnglish (US)
Pages (from-to)862-868
Number of pages7
JournalPain
Volume153
Issue number4
DOIs
Publication statusPublished - Apr 2012

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Keywords

  • ABT-894
  • Neuronal nicotinic receptor
  • Neuropathic pain
  • Randomized clinical trial

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

Cite this

Rowbotham, M. C., Arslanian, A., Nothaft, W., Duan, W. R., Best, A. E., Pritchett, Y., ... Stacey, B. R. (2012). Efficacy and safety of the α 4β 2 neuronal nicotinic receptor agonist ABT-894 in patients with diabetic peripheral neuropathic pain. Pain, 153(4), 862-868. https://doi.org/10.1016/j.pain.2012.01.009