US-based biopharmaceutical firm Cara Therapeutics has dosed the first dialysis patients in a Phase II trial of an intravenous (IV) formulation of its peripherally selective kappa opioid agonist, CR845, to treat uremic pruritus.
The double-blind, randomised, placebo-controlled trial is designed to assess the safety and pharmacokinetics (PK) of intravenous CR845 in hemodialysis patients, as well as its efficacy in hemodialysis patients experiencing uremic pruritus.
A total of 84 dialysis patients at multiple sites in the US will be enrolled in the trial, which will be conducted in two parts.
In part A of the trial, the pharmacokinetic and safety profile of repeat doses of IV CR845 will be evaluated in hemodialysis patients for one week, while the part B will measure the efficacy of CR845 in reducing the intensity of itch in dialysis patients over a two week dosing period compared to a placebo.
The trial's primary endpoint will be the change from baseline of the average worst itching during the second week of treatment, as recorded on a visual analogue scale, while secondary endpoints will focus on quality of life measures associated with the burden of pruritus using a series of previously validated self-assessment scales.
The company is focused on developing and commercialising new chemical entities designed to selectively target peripheral kappa opioid receptors, and intends to report top-line data from the trial in the first half of 2015.
Cara Therapeutics Research and Development vice-president Frédérique Menzaghi said: "The initiation of this uremic pruritus study is an important step in establishing the potential clinical utility of CR845 in this area of significant unmet medical need.
"Preclinical studies with CR845 across a range of pruritus models, as well as clinical data with other kappa agonists, indicate that CR845 may provide a novel therapeutic approach for patients suffering the burden of chronic pruritus associated with chronic kidney disease, as well as a wide spectrum of other clinical conditions."
In the US, currently there are no approved treatments 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 company said that in the multiple randomised, double-blind, placebo-controlled Phase II trials in patients undergoing laparoscopic hysterectomy or bunionectomy procedures, IV CR845 treatment resulted in statistically significant reductions in pain intensity and opioid-related side effects.