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A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain
Journal article   Open access   Peer reviewed

A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain

Dan Ziegler, W. Rachel Duan, Guohua An, James W Thomas and Wolfram Nothaft
Pain (Amsterdam), Vol.156(10), pp.2013-2020
10/2015
DOI: 10.1097/j.pain.0000000000000263
PMCID: PMC4770341
PMID: 26067585
url
https://doi.org/10.1097/j.pain.0000000000000263View
Published (Version of record) Open Access

Abstract

Supplemental Digital Content is Available in the Text. Treatment with ABT-639 100 mg for 6 weeks did not significantly reduce pain in patients with diabetic peripheral neuropathy. T-type Ca v 3.2 calcium channels represent a novel target for neuropathic pain modulation. Preclinical studies with ABT-639, a peripherally acting highly selective T-type Ca v 3.2 calcium channel blocker, showed dose-dependent reduction of pain in multiple pain models. ABT-639 also demonstrated an acceptable safety profile at single- and multiple-dose levels evaluated in a clinical phase 1 study in healthy volunteers. The primary objective of this phase 2, multicenter, randomized, double-blind, placebo-controlled, and active-controlled study was to compare the analgesic efficacy and safety of ABT-639 with placebo in the treatment of diabetic neuropathic pain. Pregabalin, an approved treatment for painful diabetic neuropathy, was included as a positive control. A total of 194 patients were randomized and treated for 6 weeks; 62 patients received ABT-639 (100 mg twice daily), 70 patients received pregabalin (150 mg twice daily), and 62 patients received placebo. When assessing the mean changes from baseline in patient-recorded pain scores at the end of week 6, there was no significant difference observed for ABT-639 compared with placebo (−2.28 vs −2.36; P = 0.582). Pregabalin treatment resulted in a transient improvement in pain compared with placebo, which did not persist throughout the study. There were no significant safety issues identified with ABT-639. A majority of adverse events were considered mild to moderate in intensity. In conclusion, treatment with the highly selective T-type Ca v 3.2 calcium channel blocker ABT-639 100 mg twice daily for 6 weeks showed no safety signals that would preclude further investigation but did not reduce neuropathic pain in patients with diabetes ( ClinicalTrials.gov identifier: NCT01345045).
Research Paper ABT-639 Diabetic neuropathic pain T-type calcium channels

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