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

Cara Therapeutics, Inc.(Nasdaq: CARA), a biotechnology company focused on developing andcommercializing new chemical entities designed to selectively targetperipheral kappa opioid receptors, today announced the successful completionof a Phase 1b trial of an intravenous (I.V.) formulation of CR845 in dialysispatients. In the repeat dosing of I.V. CR845 over one week was observed to besafe and well-tolerated across a five-fold dose range, and the trialestablished a dosing regimen for the ongoing Phase 2 trial in dialysispatients with uremic pruritus. The company expects to report top-line datafrom this trial in the first half of 2015."The completion of this Phase 1b trial and initiation of the Phase 2 study inuremic pruritus is an important step in establishing the potential clinicalutility of CR845 in this area of significant unmet medical need," saidFrédérique Menzaghi, Ph.D., Vice President of Research and Development atCara Therapeutics. "We are particularly encouraged that preliminary data fromthis trial indicate that CR845 effectively reduced "worst itching" scores inthose subjects who entered the study with ongoing moderate-to-severe uremicpruritus. We look forward to reporting top-line data from our Phase 2 trial inthe first half of 2015."There are currently no approved therapeutics in the United States for uremicpruritus, an intractable type of itch that is generally resistant toconventional treatments, and diminishes the quality of life for almost half ofall kidney dialysis patients.The Phase 1b trial was a double‐blind, randomized, placebo‐controlled trialdesigned to evaluate the safety and pharmacokinetics (PK) of I.V. CR845 in 24hemodialysis patients. I.V. CR845 was administered as a bolus dose (0.5ug-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 linearincreases in Cmax and AUC with an approximate 10-fold increase in AUC acrossdoses in these dialysis patients compared to normal subjects.I.V. CR845 was observed to be safe and well tolerated over the one-week dosingperiod with no serious adverse events (AEs) reported. The most common AEs weretransient facial tingling and headache. Although uremic pruritus was not aninclusion criterion for randomization, three subjects entered the trial with"worst itching" baseline scores in the moderate-to-severe range, >4.0 on a10.0 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 theone-week dosing period with reported "worst itching" scores of 1.0 or less."We are very encouraged that our clinical data to date in hemodialysispatients indicate that CR845 may provide a novel therapeutic approach forpatients suffering the burden of chronic pruritus associated with chronickidney disease," said Derek Chalmers, Ph.D., D.Sc., President and ChiefExecutive Officer of Cara Therapeutics. "The ability to broaden the potentialclinical utility of CR845 beyond pain into the spectrum of conditionsassociated with chronic pruritus is a significant opportunity, and we lookforward to seeing the data from this additional set of patients with uremicpruritus next year."The ongoing Phase 2 trial will measure the efficacy of I.V. CR845 compared toplacebo 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. Theprimary 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 aVAS. Secondary endpoints will focus on quality of life measures associatedwith pruritus burden using a series of previously validated self-assessmentscales. The study will enroll a total of 60 dialysis patients at multiplesites in the U.S.