Abstract: FR-PO875
Randomized, Placebo-Controlled Study on the Efficacy of CR845 in Reducing CKD-Associated Pruritus in Hemodialysis Patients
Session Information
- Dialysis: Epidemiology, Outcomes, Clinical Trials - Non-Cardiovascular - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Dialysis
- 607 Dialysis: Epidemiology, Outcomes, Clinical Trials - Non-Cardiovascular
Authors
- Spencer, Robert H., Cara Therapeutics, Inc., Stamford, Connecticut, United States
- Munera, Catherine, Cara Therapeutics, Inc., Stamford, Connecticut, United States
- Oberdick, Maria S, Cara Therapeutics, Inc., Stamford, Connecticut, United States
- Stauffer, Joseph W., Cara Therapeutics, Inc., Stamford, Connecticut, United States
- Menzaghi, Frederique, Cara Therapeutics, Inc., Stamford, Connecticut, United States
Background
With no treatment approved in the US, patients with chronic kidney disease-associated pruritus continue to be afflicted by this debilitating condition. The present study evaluated the anti-pruritic efficacy of the novel potent and selective peripherally-acting kappa-opioid receptor agonist CR845 in hemodialysis (HD) patients with moderate-to-severe pruritus.
Methods
174 HD patients experiencing pruritus for ~4.4 years with a mean baseline numerical rating score (NRS) >4 for worst itching intensity (0 [no itching] to 10 [worst itching imaginable]) were enrolled across 33 dialysis centers. 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 session over an 8-week treatment period. The primary efficacy endpoint was the change in the weekly mean of the daily 24-hour worst itching intensity NRS score from baseline (one week mean prior to randomization) to Week 8.
Results
Demographics and baseline features were well balanced across treatment groups, and CR845 was well tolerated at all doses. Average reduction in itch NRS scores from baseline (LS Mean ± SE) ranged from -2.8 (±0.38) in the 1.0 mcg/kg group (95% CI: -3.5 to -2.0) to -3.8 (±0.38) in the 0.5 mcg/kg group (95% CI: -4.5 to -3.1), with no significant differences between doses. The reduction in itch NRS scores was significantly different from placebo at the 0.5 and 1.5 mcg/kg dose (p≤ 0.019) with 64% (p=0.016) of patients in the 0.5 mcg/kg dose group reporting ≥ 30% reduction in worst itch NRS scores by Week 8, compared to 38% of the placebo patients. These results were supported by a significantly higher proportion of CR845 patients reporting that their itch was “very much improved” or “much improved” at the end of the study compared to placebo (66% CR845 vs 42% placebo; p=0.007) as measured by the Patient Global Impression of Change, along with a significant improvement in quality of life, including quality of sleep.
Conclusion
CR845 effectively and safely reduced itch intensity in HD patients with moderate-to-severe pruritus over 2 months of treatment.
Funding
- Commercial Support –