Cara Therapeutics Reports Positive Top-Line Results from Phase 1a/1b Trial of Formulation of Oracl CR845

Cara Therapeutics, Inc. CARA, a biopharmaceutical company focused on developing and commercializing new chemical entities designed to alleviate pain and pruritus by selectively targeting kappa opioid receptors, today announced the successful completion of a Phase 1a / 1b clinical trial of an oral tablet formulation of its peripherally-selective kappa opioid agonist, CR845, for the treatment of acute and chronic pain. The double-blind, randomized, placebo-controlled trial evaluated the pharmacokinetic and safety profile of single and multiple escalating doses of Oral CR845 in 150 healthy volunteers at a single U.S. site. The single ascending dose study, which included six tablet strengths ranging from 0.1 mg to 10 mg, demonstrated a mean oral bioavailability of 10% across all dose groups under fasting conditions, with a range of maximum plasma concentrations of CR845 bracketing the concentrations seen in previously successful Phase 2 trials with I.V. CR845. All tested dose strengths were also shown to be active at the kappa opioid receptor, as assessed by statistically significant (p<0.0001) acute changes in blood measurements of an established neuroendocrine biomarker. The multiple ascending dose study, which used repeat dose studies of the 0.1 mg, 1 mg and 5 mg tablets, administered twice a day (b.i.d.) for one week, demonstrated that all tablet doses were well tolerated with no serious adverse events (SAEs) reported and all adverse events (AEs) were mild and generally similar to those reported with I.V. CR845. Additionally, clinical safety laboratory measurements were normal across all tablet strengths after single or repeat dosing. "Successful completion of this Phase 1 trial of the tablet formulation of Oral CR845 represents a key milestone for Cara as we look to expand the clinical development of CR845 beyond the treatment of acute pain in a hospital setting," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "We are very encouraged that the plasma levels of CR845 attained within this tablet strength range equaled or exceeded those previously associated with clinical analgesic effects seen in acute post-operative pain models with I.V. CR845." Dr. Chalmers also noted, "These findings complement our recently successful human abuse liability study of I.V. CR845, as well as our recently completed quantitative primary research study indicating that Oral CR845 has the potential to meet a significant physician demand for a safer, non-abusable alternative to narcotic opioids and NSAIDs for the treatment of moderate-to-severe acute and chronic pain."