Pain
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Randomized Controlled Trial Multicenter Study Comparative Study
Efficacy and safety of the α4β2 neuronal nicotinic receptor agonist ABT-894 in patients with diabetic peripheral neuropathic pain.
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(4)β(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. ⋯ 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(4)β(2) NNR agonist ABT-594, which demonstrated efficacy compared with placebo, albeit with significant tolerability limitations. The failure of the highly selective α(4)β(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(4)β(2) NNRs may not be a viable approach to treating neuropathic pain.