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Abstract: TH-PO245

Difelikefalin Improved Quality of Life (5-D Itch Scale-Domains) in Hemodialysis Patients with Pruritus in an 8-Week Phase 2 Randomized, Placebo-Controlled Study

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Fishbane, Steven, Northwell Health, Commack, New York, United States
  • Spencer, Robert H., Cara Therapeutics, Inc., Stamford, Connecticut, United States
  • Munera, Catherine, Cara Therapeutics, Inc., Stamford, Connecticut, United States
  • Menzaghi, Frederique, Cara Therapeutics, Inc., Stamford, Connecticut, United States
Background

Among patients with chronic kidney disease (CKD) undergoing hemodialysis (HD), >40% have moderate-to-severe pruritus, which is associated with poor quality of life (QoL). Difelikefalin (DFK; CR845) is a selective kappa opioid receptor agonist that acts peripherally with a dual anti-inflammatory/antipruritic effect and to date has negligible abuse potential. In a Phase 2 study of HD patients with CKD associated pruritus, it was previously reported that DFK significantly reduced itch intensity. Itch reduction, assessed by the Worst Itching Intensity Numerical Rating Scale (WI-NRS) score correlated with significant improvements in itch-related QoL measures, as measured by the Skindex-10 and 5-D Itch scales. To further characterize the impact of itch reduction on patient QoL, we present results using the 5-D Itch scale domains.

Methods

Patients were randomized 1:1:1:1 to receive an IV bolus of DFK 1.5, 1.0, 0.5 mcg/kg or placebo (PBO), at the end of each dialysis over an 8-week (Wk) treatment period. The 5-D Itch scale domains were used to measure Degree, Duration, Direction [change over time of itch], Disability [sleep, leisure/social, housework/errands, work/school], and Distribution [body location of itch] – each ranked on a 5-point increasing severity scale. This analysis focused on the 0.5 mcg/kg dose that was advanced into Phase 3 studies.

Results

Patients treated with DFK 0.5 mcg/kg (n=44) exhibited a clinically meaningful improvement in 5-D Itch total scores vs PBO (n=45) at Wk 8 (-5.7 vs -2.8 LS mean [p<0.001 vs PBO]), with a significant correlation between WI-NRS and 5-D total scores (r= 0.71, p<0.0001). Except for Distribution (-0.6 vs -0.4 [p=0.368]), significant improvements from baseline were reported across all subdomains in DFK vs PBO groups at the end of Wk 8; Degree: -1.1 vs -0.5 [p<0.001 vs PBO]; Duration: -1.2 vs -0.6 [p=0.003]; Direction: -1.6 vs -0.7 [p<0.001]; Disability: -1.2 vs -0.5 [p=0.004].

Conclusion

This analysis further characterized the impact of itch severity reduction with DFK indicating significant improvement in QoL as measured by the 5-D Itch multidimensional questionnaire. Results demonstrate itch intensity reduction with DFK is associated with improved QoL.

Funding

  • Commercial Support