Cizolirtine citrate (E-4018) in the treatment of chronic neuropathic pain.
This study was performed to determine the efficacy and safety of oral cizolirtine citrate, a novel agent, in the treatment of chronic neuropathic pain. Cizolirtine was tested in a double-blind, placebo-controlled, two-way crossover study, having previously been shown to have significant analgesic and anti-hyperalgesic action in neuropathic pain models and preliminary human studies. Twenty-five patients with neuropathic pain, which was persistent for at least three months, and scored > 30 mm on a 100 mm visual analogue scale (VAS), were included. A subgroup of five patients had primary skin allodynia, i.e. pain evoked by non-noxious stimuli in the territory of the injured nerve. Cizolirtine 200 mg or placebo was administered twice daily for a treatment period of 21 days, each separated by a washout interval of 7 days. Assessments of skin allodynia were performed using the graded monofilaments (von Frey hairs) on days 1 (predose), 14 and 21 (90 min postdose). All patients were instructed to maintain a daily pain diary throughout the study. Results showed that the differences in VAS and allodynia scores between cizolirtine and placebo treatments were not significant in the overall analysis (p > or = 0.05); cizolirtine was well tolerated. In a subgroup of five patients with primary allodynia, a 53% reduction in VAS score from baseline at rest (p = 0.007) and 55% on movement (p = 0.0002) at day 21 was observed with cizolirtine, as compared to 8% at rest (p = 0.5215) and 13% on movement (p = 0.4187) with placebo. Similarly, allodynia improved with cizolirtine (p = 0.03) but not with placebo (p = 0.9) in this subgroup. Cizolirtine may be effective in primary allodynia after peripheral nerve injury, and a further trial in a larger number of such subjects is warranted.
Shembalkar
P
P
Department of Neurology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Täubel
J
J
Abadias
M
M
Arezina
R
R
Hammond
K
K
Anand
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D011720:Pyrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D011720:Pyrazoles; C075798:cizolirtine