Discussion
ICH, pruritus, chronic liver failure, treatment-resistant
PATHOGENESIS
Our present study, as a bridging study, met its predefined success criterion (difference of VAS decreases greater than 4.13 mm, retained at least 50% of the efficacy of the key clinical trial in Japan), in line with requirements for the bridging study from the Chinese regulator. To the best of our knowledge, this is the first report on the safety and efficacy of nalfurafine in Chinese subjects. The strength of our study also included the prospective study design and hemodialysis patients from multiple centers. Thus, we could validly concluded that the efficacy results of this bridging trial were consistent with the results of the Japanese phase III trial, in accordance with the ICH guidelines [Although the design of our study was similar to the previous study conducted in Japan [A bridging study can be carried out to ‘build a bridge’ with foreign clinical data. The regulatory issues required by the Chinese National Medical Products Administration and long clinical testing and approval time for drugs to be marketed in China continue to be stumbling blocks for foreign drugs in the Chinese market. The ICH E5 guidelines [The pathogenesis of CKD-aP remained to be fully elucidated, thus developing effective therapeutic agents was quite tough. The current treatment options for intractable pruritus in patients with hemodialysis, which include topical treatment, antihistamines and antiallergic agents, phototherapy, specifically selected dialysis membranes, or performing hemodiafiltration, are not sufficiently effective [In clinical studies, nalfurafine has been demonstrated to present a prominent efficacy for intractable pruritus in chronic liver failure [The safety profile of nalfurafine observed in the present study remained similar to that outlined in the studies carried out in the CKD-aP population of Japan [This trial had certain limitations. The trial enrolled patients in whose gender were male predominance in each group. Although there were total of 141 cases enrolled in our study and the sample size was considered to be effective to meet the predefined success criteria of our bridging trial, the sample size was smaller than the Japanese trial of more than 300 cases. The safety and efficacy of nalfurafine were assessed for 22 days in this trial that was similar with the Japanese trial. Assessments over longer durations including Chinese patients will help support the generalizability of this treatment.In summary, the results of this prospective randomized, placebo-controlled multicenter bridging study did show efficacy of nalfurafine administration for treatment-resistant CKD-aP in Chinese population undergoing hemodialysis based on predefined criterion. The safety profile of nalfurafine was consistent with that observed in previous studies, and no new safety issues had been proposed. Nalfurafine was found to be an effective and safe treatment option for Chinese hemodialysis patients with pruritus in this study.