Array BioPharma Inc. has commenced dosing ARRY-797, a novel, small molecule p38 inhibitor, in a phase II clinical trial to evaluate the efficacy of this drug for treating pain in dental patients undergoing third molar extraction.
"I am delighted that we are now dosing patients in our phase II study to evaluate the efficacy of ARRY-797 in the management of postoperative dental pain," said John Yates, MB ChB, MD, chief medical officer, Array BioPharma. "We believe we are likely to see significant efficacy in acute pain based upon ARRY-797's pharmacodynamic activities to date. This model has been a good predictor of acute analgesic effects of various pain medications".
The phase II trial is a randomised, double-blind, placebo-controlled, parallel-group efficacy study of ARRY-797 in dental patients undergoing third molar extraction. The objective of the study is to assess the safety, tolerability and analgesic efficacy of ARRY-797 dosed either after the operation or both before and after surgery. Although analgesics are typically administered with the onset of pain, emerging evidence suggests that dosing an anti-inflammatory drug prior to a surgical procedure can help block the development of pain. The trial will enrol 150 patients and be conducted at two centres in the United States.ARRY-797 / p38 Inhibitor phase I
In a single ascending dose (SAD) study in healthy volunteers, ARRY-797 was shown to have linear increases in exposure with increasing oral dose; the dose range studied was from 25 to 400 mg. The drug was well-tolerated with no serious adverse events. In blood samples taken from these volunteers and stimulated ex vivo, ARRY-797 was shown to inhibit the production of IL-1beta, TNF-alpha and PGE2. These effects were pronounced, with up to 80 to 90 percent inhibition of these inflammatory mediators seen at the higher doses. ARRY-797 met its objective in this study and is nearing completion in a multiple ascending dose (MAD) study in normal volunteers.
Targeting p38 for Inflammation and PainP38 is a kinase target that regulates the production of numerous pro-inflammatory cytokines, in particular, TNF, IL-1, IL-6 and PGE2. Based upon its potential to reduce the synthesis of multiple pro-inflammatory mediators from diverse cell types and block key secondary inflammatory pathways at an early stage, blockade of p38 kinase activity provides a novel therapeutic approach for the treatment of inflammation and inflammatory pain.
Array BioPharma Inc. is a biopharmaceutical company focused on the discovery, development and commercialisation of targeted small molecule drugs to treat patients afflicted with cancer and inflammatory diseases. Our proprietary drug development pipeline includes clinical candidates that are designed to regulate therapeutically important target proteins and are aimed at large market opportunities. In addition, leading pharmaceutical and biotechnology companies collaborate with Array to discover and develop drug candidates across a broad range of therapeutic areas.