Statistical analysis
SECONDARY
The predefined success criteria of our bridging trial was the difference of VAS decreases greater than 4.13 mm, retained at least 50% of the efficacy (8.26 mm) of the key clinical trial in Japan. To meet the primary purpose of this bridging trial, by assuming an expected difference of 8.26 mm in the change in VAS values, with the standard deviation of 20mm and a statistical power of 80%, the sample size of 125 Chinese patients were needed in the FAS: among them, 50 cases were in the 5 μg dose group of nalfurafine, 50 cases were in the 2.5 μg group, and 25 cases were in the placebo group.The FAS was the main population for efficacy analysis. It included all participants who were randomized, received at least one dose of the study drug, and evaluated of post-treatment efficacy at least once. The per protocol set (PPS) was a subset of the full analysis set and included all subjects who met the inclusion/exclusion criteria specified in the protocol, had good compliance, and had no major protocol deviations during the trial. The PPS set was a secondary population for efficacy analysis. The safety analysis set (SS) included all randomized participants who received at least one dose of the study drug, and obtained safety assessment at least once.In the primary endpoint analysis, the missing data were imputed with the use of the last-observation-carried-forward (LOCF) method. And in the analysis of secondary endpoint the missing data were not imputed. It is a bridging clinical study. The primary endpoint goal is that the difference of the change in average VAS between the study group and the placebo control group is no less than 4.13 mm (at least should get the 50% of the curative effect in the key phase III clinical trial in Japan). The results of bridging study will be tested by the fixed sequence test method, the 5 μg nalfurafine to placebo groups and the 2.5 μg nalfurafine to placebo groups will be tested respectively. The analysis of covariance (ANCOVA) method was used for comparison between groups. The average value of the larger value of VAS measured at the time of getting up and going to bed in the latter seven-day pre-observation period was used as the covariate. The two-sided 95% confidence interval (CI) was determined for the intergroup difference in the mean VAS values. Statistical analyses were performed using SAS version 9.4.