Nalfurafine hydrochloride for refractory pruritus in peritoneal dialysis patients: a phase III, multi-institutional, non-controlled, open-label trial

Background: Nalfurafine hydrochloride (“nalfurafine”), the world’s first selective oral κ-receptor agonist for improving pruritus, is approved in Japan for the treatment of pruritus resistant to existing treatments in hemodialysis (HD) or chronic liver disease patients. Peritoneal dialysis (PD) patients, like HD patients, suffer from end-stage renal disease (ESRD) and some experience refractory pruritus. Methods: We investigated the efficacy and safety of nalfurafine in 37 ESRD patients who underwent PD and had refractory pruritus. Nalfurafine was given once daily for 4 weeks at 2.5 μg in weeks 1 and 2 of the treatment period and at 5 μg in weeks 3 and 4. The primary endpoint was visual analog scale (VAS) changes for pruritus (i.e., the value upon rising or before sleep in week 2, whichever larger). Results: The mean VAS change from baseline in week 2 of the treatment period was 24.93 mm [18.67, 31.19] (the point estimate of the mean [90% confidence interval (CI)]); the lower limit of CI exceeded the point estimate of the mean VAS change (15.24 mm) of the placebo group at the evaluation point (week 2) in a preceding confirmatory trial suggesting that had demonstrated nalfurafine efficacy for refractory pruritus in HD patients. The observed VAS change was comparable to that of the 2.5-μg group (week 2) in the preceding confirmatory trial, demonstrating that nalfurafine is as effective for treating pruritus in PD patients as in HD patients. Nalfurafine 5 μg was associated with a mean VAS change of 32.13 mm at week 4, i.e., the full length of the trial treatment period suggesting efficacy at the dose of 5 μg. The incidence of adverse drug reactions (ADR) was 45.9% (1/37 patients) with no serious ADRs observed. ADRs occurring in ≥ 5% of patients included insomnia (13.5%), increased blood prolactin (13.5%), somnolence (8.1%), lower blood testosterone free (8.1%), and vomiting (5.4%), all of which were mild. Conclusions: This trial demonstrated the efficacy and safety of nalfurafine against refractory pruritus in PD, suggesting clinical benefit for treating pruritus in PD patients. Trial registration: Japan Pharmaceutical Information Center, JapicCTI-142565