Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study.
BACKGROUND
Pruritus in haemodialysis patients is an intractable disease and substantially impairs their quality of life. Based on the results of our earlier clinical study, we hypothesized that the micro-(mu) opioid system is itch-inducible, whereas the kappa (kappa) system is itch-suppressive.


METHODS
The efficacy and safety of nalfurafine hydrochloride (a novel kappa-receptor agonist) were prospectively investigated by randomly (1:1:1) administering 5 or 2.5 microg of the drug or a placebo orally for 14 days using a double-blind design in 337 haemodialysis patients with itch that was resistant to currently available treatments, such as antihistamines.


RESULTS
The mean decrease in the visual analogue scale (VAS) from baseline, the study's primary endpoint, was significantly larger in the 5-microg nalfurafine hydrochloride group (n = 114) than in the placebo group (n = 111, P = 0.0002, one-sided test at 2.5% significance level). The decrease in the VAS in the 2.5-microg group (n = 112) was also significantly larger than that in the placebo group (P = 0.0001). The incidence of adverse drug reactions (ADRs) was 35.1% in the 5-microg group, 25.0% in the 2.5-microg group and 16.2% in the placebo group. Moderate to severe ADRs were observed in 10 of the 226 patients. The most common ADR was insomnia (sleep disturbance), seen in 24 of the 226 nalfurafine patients.


CONCLUSIONS
This Phase III, randomized, double-blind, placebo-controlled, parallel-group, prospective study based on VAS evaluations clearly showed that orally taken nalfurafine hydrochloride effectively reduced itches that were otherwise refractory to currently available treatments in maintenance haemodialysis patients, with few significant ADRs. This novel drug was officially approved for clinical use in January 2009 by the Ministry of Health, Labour and Welfare of Japan.
Kumagai
Hiroo
H
Department of Nephrology, National Defense Medical College, Japan. hkumagai@ndmc.ac.jp
Ebata
Toshiya
T
Takamori
Kenji
K
Muramatsu
Taro
T
Nakamoto
Hidetomo
H
Suzuki
Hiromichi
H
D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000627:therapeutic use*; D010919:Placebos; D011446:Prospective Studies; D011537:Pruritus / Q000188:drug therapy* / Q000209:etiology; D017473:Receptors, Opioid, kappa / Q000819:agonists; D006435:Renal Dialysis / Q000009:adverse effects*; D013141:Spiro Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
D009019:Morphinans; D010919:Placebos; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820