Cara Therapeutics Announces Positive Top-Line Data from Phase 1b Trial of IV CR845

Cara Therapeutics, Inc.

, a biotechnology company focused on developing and commercializing new chemical entities designed to selectively target peripheral kappa opioid receptors, today announced the successful completion of a Phase 1b trial of an intravenous (I.V.) formulation of CR845 in dialysis patients. In the repeat dosing of I.V. CR845 over one week was observed to be safe and well-tolerated across a five-fold dose range, and the trial established a dosing regimen for the ongoing Phase 2 trial in dialysis patients with uremic pruritus. The company expects to report top-line data from this trial in the first half of 2015. "The completion of this Phase 1b trial and initiation of the Phase 2 study in uremic pruritus is an important step in establishing the potential clinical utility of CR845 in this area of significant unmet medical need," said Frédérique Menzaghi, Ph.D., Vice President of Research and Development at Cara Therapeutics. "We are particularly encouraged that preliminary data from this trial indicate that CR845 effectively reduced "worst itching" scores in those subjects who entered the study with ongoing moderate-to-severe uremic pruritus. We look forward to reporting top-line data from our Phase 2 trial in the first half of 2015." There are currently no approved therapeutics in the United States for uremic pruritus, an intractable type of itch that is generally resistant to conventional treatments, and diminishes the quality of life for almost half of all kidney dialysis patients. The Phase 1b trial was a double‐blind, randomized, placebo‐controlled trial designed to evaluate the safety and pharmacokinetics (PK) of I.V. CR845 in 24 hemodialysis patients. I.V. CR845 was administered as a bolus dose (0.5 ug-2.5ug/kg) after each dialysis session up to three times a week (t.i.w.). Pharmacokinetic analysis indicated that I.V. CR845 exhibited dose linear increases in Cmax and AUC with an approximate 10-fold increase in AUC across doses in these dialysis patients compared to normal subjects. I.V. CR845 was observed to be safe and well tolerated over the one-week dosing period with no serious adverse events (AEs) reported. The most common AEs were transient facial tingling and headache. Although uremic pruritus was not an inclusion criterion for randomization, three subjects entered the trial with "worst itching" baseline scores in the moderate-to-severe range, >4.0 on a 10.0 point visual analog scale (VAS). All three subjects received t.i.w. dosing of I.V. CR845 (two subjects at 1ug/kg, one at 2.5ug/kg) and ended the one-week dosing period with reported "worst itching" scores of 1.0 or less. "We are very encouraged that our clinical data to date in hemodialysis patients indicate that CR845 may provide a novel therapeutic approach for patients suffering the burden of chronic pruritus associated with chronic kidney disease," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "The ability to broaden the potential clinical utility of CR845 beyond pain into the spectrum of conditions associated with chronic pruritus is a significant opportunity, and we look forward to seeing the data from this additional set of patients with uremic pruritus next year." The ongoing Phase 2 trial will measure the efficacy of I.V. CR845 compared to placebo in reducing the intensity of itch in dialysis patients with baseline "worst itching" scores of 4.0 or greater over a two-week dosing period. The primary endpoint of the study will be the change from baseline in the average "worst itching" scores during the second week of treatment, as recorded on a VAS. Secondary endpoints will focus on quality of life measures associated with pruritus burden using a series of previously validated self-assessment scales. The study will enroll a total of 60 dialysis patients at multiple sites in the U.S.