Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study.
OBJECTIVE
To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain.


METHODS
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.
Nerve and Muscle Center of Texas, Baylor College of Medicine, 6624 Fannin Street #1670, Houston, TX 77030, USA. shaibani@bcm.edu
Aziz I
AI
Shaibani
Laura E
LE
Pope
Ronald
R
Thisted
Adrian
A
Hepner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003915:Dextromethorphan / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011802:Quinidine / Q000008:administration & dosage* / Q000009:adverse effects
D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D010919:Placebos; C507057:dextromethorphan - quinidine combination; D003915:Dextromethorphan; D011802:Quinidine