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: Dan Ziegler, W Rachel Duan, Guohua An, James W Thomas, Wolfram Nothaft
• Journal: Pain (Pain) Vol. 156 Issue 10 Pg. 2013-2020 (Oct 2015) ISSN: 1872-6623 [Electronic] United States
• PMID: 26067585 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 4-chloro-2-fluoro-N-(2-fluorophenyl)-5-(hexahydropyrrolo(1,2-a)pyrazin-2(1H)-ylcarbonyl)benzenesulfonamide
• Calcium Channel Blockers
• Heterocyclic Compounds, 2-Ring
• Sulfonamides

Topics

• Adolescent
• Adult
• Aged
• Calcium Channel Blockers (pharmacokinetics, therapeutic use)
• Diabetic Neuropathies (drug therapy, psychology)
• Double-Blind Method
• Female
• Heterocyclic Compounds, 2-Ring (pharmacokinetics, therapeutic use)
• Humans
• Male
• Middle Aged
• Pain Measurement
• Quality of Life (psychology)
• Sulfonamides (pharmacokinetics, therapeutic use)
• Treatment Outcome
• Young Adult