title: A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain.
abstract: 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).
authors.affiliation: Institute 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 AbbVie Inc, North Chicago, IL, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Ziegler
authors.forename: W Rachel
authors.initials: WR
authors.lastname: Duan
authors.forename: Guohua
authors.initials: G
authors.lastname: An
authors.forename: James W
authors.initials: JW
authors.lastname: Thomas
authors.forename: Wolfram
authors.initials: W
authors.lastname: Nothaft
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006574:Heterocyclic Compounds, 2-Ring / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011788:Quality of Life / Q000523:psychology; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D000096926:Benzenesulfonamides
chemical_list: D002121:Calcium Channel Blockers; D006574:Heterocyclic Compounds, 2-Ring; D013449:Sulfonamides; C000589982:4-chloro-2-fluoro-N-(2-fluorophenyl)-5-(hexahydropyrrolo(1,2-a)pyrazin-2(1H)-ylcarbonyl)benzenesulfonamide; D000096926:Benzenesulfonamides