Difelikefalin for Hemodialysis Patients with Pruritus in Japan

BACKGROUND: Difelikefalin, a peripherally specific selective agonist of kappa opioid receptors, has been approved for the treatment of pruritus in hemodialysis patients in the United States. However, there is limited evidence for postdialysis intravenous use in non-U.S. populations. METHODS: In this double-blind, placebo-controlled, phase 3 trial in Japan, patients with moderate to severe pruritus were randomly allocated 1:1 to receive either placebo or 0.5 μg/kg of difelikefalin three times per week intravenously for 6 weeks. The primary end point was change from baseline in the Worst Itching Intensity Numerical Rating Scale (NRS; 0 to 10; higher scores indicate more severe itching) score at week 4. RESULTS: A total of 230 patients were screened, of whom 178 were randomly assigned to receive placebo (n=89) or difelikefalin (n=89). The change from baseline in the weekly adjusted mean NRS score (95% confidence interval) at week 4 in the placebo and difelikefalin groups was −1.09 (−1.47 to −0.70) and −2.06 (−2.45 to −1.66), respectively. The difference between the groups was −0.97 (−1.52 to −0.42), demonstrating that difelikefalin was superior to placebo (P<0.001). Prespecified secondary quality-of-life end points showed consistent improvement associated with difelikefalin. The incidence of treatment-related adverse events in the placebo and difelikefalin groups was 3 of 89 patients (3%) and 13 of 89 patients (15%), respectively, of which the majority in the difelikefalin group were gastrointestinal (e.g., constipation and abdominal discomfort). CONCLUSIONS: Intravenous difelikefalin reduced itching and improved quality of life in patients with moderate to severe pruritus who were undergoing maintenance hemodialysis. (Funded by Kissei Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT04711603.)