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Abstract: TH-PO247

Difelikefalin Significantly Reduced Sleep Disturbance in Hemodialysis Patients with Moderate-to-Severe Pruritus in an 8-Week Phase 2, Randomized, Placebo-Controlled Study

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Bhaduri, Sarbani, CARA, El Paso, Texas, 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

Patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) often have CKD-associated pruritus (CKD-aP), a debilitating chronic systemic itch. More than 40% of CKD patients suffer from moderate-to-severe itch with associated poor quality of life (QoL) and sleep disturbance.4 Sleep disturbance in CKD is associated with an increased mortality risk.5 Difelikefalin (DFK, CR845) is a selective kappa opioid receptor agonist that acts peripherally with dual anti-inflammatory and antipruritic effects. In an 8-week Phase 2 study in HD patients with moderate-to-severe pruritus, DFK demonstrated significant efficacy in reducing itch intensity and improved itch-related QoL measures. To further characterize the impact of itch reduction with DFK, we report results regarding changes in sleep disturbance.

Methods

Patients were randomized 1:1:1:1 to receive an intravenous bolus injection of DFK 1.5, 1.0, or 0.5 mcg/kg, or PBO at the end of each dialysis over an 8-week treatment period. The sleep disturbance subscale is part of the MOS sleep scale (MOS-S) and focuses on trouble falling asleep, sleep restlessness, awakening during sleep, and time to fall asleep during the past week. The MOS-S was administered on Day 1 (predose) and at Week (Wk) 4, Wk 8, and at the end of treatment (EOT, Day 57). This analysis focused on the DFK 0.5 mcg/kg dose, which was advanced into Phase 3 studies.

Results

Patients treated with DFK exhibited a significant reduction in sleep disturbance compared with PBO, with a mean change from baseline in DFK 0.5 mcg/kg (n=44) and PBO (n=45) groups, respectively, of -8.6 vs 2.2 [p=0.013] at Wk 4; -9.8 vs -2.2 [p=0.077] at Wk 8; -13.8 vs -1.3 [p=0.006] at EOT.

Conclusion

Significantly improved MOS-S sleep disturbance scores were obtained after DFK treatment, indicating a clinically sustained improvement in sleep through Wk 8 that was associated with a robust and sustained reduction in itch intensity. The effects of DFK on sleep, as well as long-term efficacy and safety of DFK, are currently under investigation in patients with CKD-aP in ongoing Phase 3 studies.
Reference: 4Shirazian S et al. Int J Nephrol Renovasc Dis 2017;10:11; 5Benz R et al. Am J Kidney Dis 2000;35:1052

Funding

  • Commercial Support –