Randomized Controlled Trial of Difelikefalin for Chronic Pruritus in Hemodialysis Patients

  • Kidney Int Rep. 2020 Jan 28;5(5):600-610. doi: 10.1016/j.ekir.2020.01.006.
Steven Fishbane  1 ,  Vandana Mathur  2 ,  Michael J Germain  3 ,  Shayan Shirazian  4 ,  Sarbani Bhaduri  5 ,  Catherine Munera  6 ,  Robert H Spencer  6 ,  Frédérique Menzaghi  6 ,  Trial Investigators
Affiliations
  • 1. Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, USA.
  • 2. MathurConsulting, Woodside, California, USA.
  • 3. Baystate Medical Center and Tufts University, Springfield, Massachusetts, USA.
  • 4. Columbia University Medical Center, Division of Nephrology, Department of Medicine, College of Physicians and Surgeons at Columbia University, New York, New York, USA.
  • 5. Bhaduri Biotech Consulting, El Paso, Texas, USA.
  • 6. Cara Therapeutics, Inc., Stamford, Connecticut, USA.
PMID: 32405581 DOI: 10.1016/j.ekir.2020.01.006
Abstract

Introduction: There is an unmet medical need for pruritus associated with chronic kidney disease, a distressing complication characterized by generalized and persistent itch affecting 20% to 40% of patients undergoing hemodialysis. Here we report the results of a phase 2 trial evaluating the efficacy and safety of a novel peripherally restricted kappa Opioid Receptor agonist, difelikefalin, in adult patients undergoing hemodialysis with pruritus.

Methods: In this study, 174 hemodialysis patients with moderate-to-severe pruritus were randomly assigned to receive difelikefalin (0.5, 1.0, or 1.5 μg/kg) or placebo intravenously thrice weekly after each hemodialysis session for 8 weeks in a double-blind, controlled trial. The primary endpoint was the change from baseline at week 8 in the weekly mean of the 24-hour Worst Itching Intensity Numerical Rating Scale score. The secondary efficacy endpoint was the change in itch-related quality of life measured by the Skindex-10 questionnaire. Other endpoints included safety, sleep quality, and additional measures including the 5-D itch scale.

Results: A significant reduction from baseline in itch intensity scores at week 8 favored all difelikefalin doses combined versus placebo (P = 0.002). Difelikefalin also showed improvement over placebo in Skindex-10, 5-D itch, and sleep disturbance scores (P ≤ 0.005). Overall, 78% of patients receiving difelikefalin reported treatment-emergent adverse events versus 42% of patients given placebo, with diarrhea, dizziness, nausea, somnolence, and fall being the most frequent (≥5%).

Conclusion: In this trial, difelikefalin effectively reduced itching intensity and improved sleep and itch-related quality of life.

Keywords
CKD-aP; CR845; chronic kidney disease; hemodialysis; kappa opioid receptor agonist; uremic pruritus.
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