Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus

On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. Missing weekly mean WI-NRS data were imputed using missing at random (MAR) multiple imputation (MI) approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data. The percentage of participants were estimated using a logistic regression model with terms for treatment group, baseline WI-NRS score, use of anti-itch medication during the week prior to randomisation, and the presence of specific medical conditions at baseline.

On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. Missing weekly mean WI-NRS data were imputed using MAR-MI approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data.

On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values was calculated for the analysis. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline WI-NRS score as fixed continuous effects.

The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects.

The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects.

The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline skindex-10 scale score (total score) as fixed continuous effects.

The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline skindex-10 scale score (total score) as fixed continuous effects.

The Patient Global Impression of Change is a global participant reported outcome measure that assesses the change in itch (no change, improvement or worsening) overall relative to the start of the study. The scale has only 1 item, and the participant was asked to mark the category that best describes the change in itch ranging from "Very Much Improved" to "Very Much Worse". Number of participants within all individual categories are reported here.