Kidney Week

Abstract: SA-OR032

Randomized, Placebo-Controlled Study on the Efficacy of CR845 in Improving the Quality of Life of Hemodialysis Patients with CKD-Associated Pruritus

Session Information

• Non-Cardiovascular Outcomes in Hemodialysis
  November 04, 2017 | Location: Room 292, Morial Convention Center
  Abstract Time: 04:42 PM - 04:54 PM

Category: Dialysis

• 607 Dialysis: Epidemiology, Outcomes, Clinical Trials - Non-Cardiovascular

Authors

• Menzaghi, Frederique, Cara Therapeutics, Inc., Stamford, Connecticut, United States

Frederique Menzaghi, PhD



http://www.caratherapeutics.com/about/person/frederique-menzaghi-ph-d/

• Munera, Catherine, Cara Therapeutics, Inc., Stamford, Connecticut, United States

Catherine Munera,

• Oberdick, Maria S, Cara Therapeutics, Inc., Stamford, Connecticut, United States

Maria S Oberdick,

• Stauffer, Joseph W., Cara Therapeutics, Inc., Stamford, Connecticut, United States

Joseph W. Stauffer,

• Spencer, Robert H., Cara Therapeutics, Inc., Stamford, Connecticut, United States

Robert H. Spencer,

Background

Chronic kidney disease-associated pruritus is a serious itching disorder associated with poor quality of life (QOL), linked to sleep disturbance, depressed mood and increased mortality. The present trial evaluated the anti-pruritic efficacy of the novel kappa-opioid receptor agonist CR845 and its impact on QOL in hemodialysis (HD) patients suffering from moderate-to-severe pruritus.

Methods

174 HD patients with a mean baseline numerical rating score (NRS) for worst itching intensity >4 were enrolled [0=no itching up to 10=worst itching imaginable]. Patients were randomized to receive one of 3 intravenous doses of CR845 (0.5 mcg/kg, n=44; 1 mcg/kg, n=41 and 1.5 mcg/kg, n=44) or placebo (n=45) at the end of each dialysis over an 8-week treatment period. Worst itching intensity (NRS, primary endpoint) and QOL measures due to itching (secondary/exploratory endpoints) were recorded, with efficacy being defined as the change from baseline to the last week of the treatment (i.e. Week 8). Changes in QOL was assessed using multidimensional questionnaires including the Skindex-10 (with measures of emotional distress and social functioning), 5-D itch scale (with measures of sleep and social functioning) and the MOS sleep disturbance subscale.

Results

CR845 was well tolerated and reduction in itch NRS scores over placebo was observed at all doses, with a change from baseline ≥3 NRS points by end of Week 8 for 64% of the patients treated with CR845 0.5 mcg/kg vs 29% of the placebo patients (p<0.001). Improvement in QOL measures was significantly different from placebo for all doses of CR845 with respect to the Skindex-10 and the 5-D itch scale (p values ranging from <0.001 to <0.026), along with a significant improvement in sleep at doses of 0.5 and 1 mcg/kg (p=0.006). The mean change in QOL measures correlated with the change in itch intensity (Pearson’s correlation ranging from r=0.67 to 0.74, p<0.0001).

Conclusion

CR845 produced a substantial improvement in multiple measures of itch-related QOL associated with a clinically important reduction in itch intensity in HD patients with moderate-to-severe pruritus that was sustained over 2 months of treatment.

Funding

• Commercial Support – Cara Therapeutics, Inc.