Disclosures: Dr. Shaibani was an investigator for the study, paid by the sponsor, and previously presented the results of this study in abstract form at a scientific conference. Drs. Pope and Hepner are employees of Avanir Pharmaceuticals, Inc. Dr. Thisted is a statistical consultant to Avanir Pharmaceuticals, Inc. He receives book royalties from CRC Press, and has served as an expert witness on behalf of Eli Lilly, Bayer, Pronova, Genzyme, Ameritox, Otsuka, GlaxoSmithKline, Wyeth, Novartis, and Galderma.
Efficacy and Safety of Dextromethorphan/Quinidine at Two Dosage Levels for Diabetic Neuropathic Pain: A Double-Blind, Placebo-Controlled, Multicenter Study
Version of Record online: 7 FEB 2012
Wiley Periodicals, Inc.
Volume 13, Issue 2, pages 243–254, February 2012
How to Cite
Shaibani, A. I., Pope, L. E., Thisted, R. and Hepner, A. (2012), Efficacy and Safety of Dextromethorphan/Quinidine at Two Dosage Levels for Diabetic Neuropathic Pain: A Double-Blind, Placebo-Controlled, Multicenter Study. Pain Medicine, 13: 243–254. doi: 10.1111/j.1526-4637.2011.01316.x
- Issue online: 23 FEB 2012
- Version of Record online: 7 FEB 2012
- Clinical Trial;
- Diabetic Peripheral Neuropathic Pain;
- Numerical Pain Rating Scale;
Objective. To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain.
Design. In a 13-week, phase 3, randomized controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain for ≥3 months received double-blind placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. Efficacy measures included four pain rating scales applied daily using patient diaries, and another two applied at five clinic visits.
Results. On all six scales, DMQ 45/30 mg was significantly superior to placebo, including the primary efficacy analysis, which utilized mixed-effects modeling to test all scores on an 11-point numerical Pain Rating Scale (P < 0.0001). Sensitivity analyses gave consistent results. Efficacy vs placebo was also seen for diary ratings of present pain intensity, and pain interference with sleep and with activities (all P < 0.0001). Among clinic visit assessments, DMQ 45/30 mg demonstrated greater leg pain relief (P = 0.0002) and greater reduction of leg pain intensity (P = 0.0286) vs placebo. The efficacy of DMQ 30/30 mg was numerically less than for 45/30 mg but for most outcomes remained significantly greater vs placebo. Adverse events were mostly mild or moderate and of expected types. Discontinuation for adverse events in the DMQ groups was at least twice as common as placebo.
Conclusions. Throughout a 13-week trial, DMQ was effective, with an acceptable safety profile, for treatment of DPN pain. Other fixed-dose combinations of DMQ should be studied to improve overall tolerability while maintaining significant efficacy.