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

Hiroo Kumagai, Toshiya Ebata, Kenji Takamori, Taro Muramatsu, Hidetomo Nakamoto, Hiromichi Suzuki

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

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 μ-(mu) opioid system is itch-inducible, whereas the κ (kappa) system is itch-suppressive.Methods. The efficacy and safety of nalfurafine hydrochloride (a novel κ-receptor agonist) were prospectively investigated by randomly (1:1:1) administering 5 or 2.5 μg 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-μg 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-μg 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-μg group, 25.0% in the 2.5-μg 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.

Original languageEnglish
Pages (from-to)1251-1257
Number of pages7
JournalNephrology Dialysis Transplantation
Volume25
Issue number4
DOIs
Publication statusPublished - 2010 Apr

Fingerprint

kappa Opioid Receptor
Renal Dialysis
Drug-Related Side Effects and Adverse Reactions
Placebos
Visual Analog Scale
Histamine Antagonists
Sleep Initiation and Maintenance Disorders
Pruritus
Pharmaceutical Preparations
Opioid Analgesics
Japan
Sleep
Maintenance
Quality of Life
TRK 820
Prospective Studies
Safety
Incidence
Health
Therapeutics

Keywords

  • κ-receptor agonist
  • Itch
  • Nalfurafine hydrochloride
  • Randomized controlled study
  • Visual analogue scale

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

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. / Kumagai, Hiroo; Ebata, Toshiya; Takamori, Kenji; Muramatsu, Taro; Nakamoto, Hidetomo; Suzuki, Hiromichi.

In: Nephrology Dialysis Transplantation, Vol. 25, No. 4, 04.2010, p. 1251-1257.

Research output: Contribution to journalArticle

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abstract = "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 μ-(mu) opioid system is itch-inducible, whereas the κ (kappa) system is itch-suppressive.Methods. The efficacy and safety of nalfurafine hydrochloride (a novel κ-receptor agonist) were prospectively investigated by randomly (1:1:1) administering 5 or 2.5 μg 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-μg 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-μg 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-μg group, 25.0{\%} in the 2.5-μg 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.",
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T2 - A Phase III, randomized, double-blind, placebo-controlled study

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AU - Ebata, Toshiya

AU - Takamori, Kenji

AU - Muramatsu, Taro

AU - Nakamoto, Hidetomo

AU - Suzuki, Hiromichi

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AB - 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 μ-(mu) opioid system is itch-inducible, whereas the κ (kappa) system is itch-suppressive.Methods. The efficacy and safety of nalfurafine hydrochloride (a novel κ-receptor agonist) were prospectively investigated by randomly (1:1:1) administering 5 or 2.5 μg 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-μg 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-μg 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-μg group, 25.0% in the 2.5-μg 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.

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