T-type Cav3.2 calcium channels represent a novel target for neuropathic pain modulation. Preclinical studies with ABT-639, a peripherally acting highly selective T-type Cav3.2 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 Cav3.2 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).
Treatment with ABT-639 100 mg for 6 weeks did not significantly reduce pain in patients with diabetic peripheral neuropathy.
aInstitute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University; Leibniz Center for Diabetes Research; Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
bAbbVie Inc, North Chicago, IL, USA
Corresponding author. Address: German Diabetes Center, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. Tel.: 004921133820; fax: 004921133882244. E-mail address: email@example.com (D. Ziegler).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).
Received March 24, 2015
Received in revised form June 02, 2015
Accepted June 03, 2015