Development of Transnasal Ketamine for Breakthrough Pain

DESCRIPTION (provided by applicant): Pain management is rapidly becoming a major healthcare challenge. As many as 50 million to 75 million Americans suffer from chronic pain, a number that is certain to increase. In some cases, chronic pain is compounded by episodes of acute moderate-to-severe pain, which "breaks through" the around-the-clock medication administered for the treatment of chronic malignant pain. Breakthrough pain is particularly difficult to treat due to its severity, rapid onset, and frequent unpredictability. Cancer is among the most devastating conditions associated with pain. Approximately 50 percent of all cancer patients with moderate to severe pain experience breakthrough pain. The management of breakthrough pain is often poorly controlled by the analgesics currently available in the market, the most common of which are the immediate-release opioids. Given the debilitating effects of breakthrough pain, the need for a safer, more efficient, non-opioid, rapid-onset analgesic is clear. Ketamine hydrochloride is a U.S. FDA approved anesthetic that has been used in tens of thousands of patients since its introduction into clinical practice greater than 30 years ago. At sub-anesthetic plasma concentrations, ketamine acts as a potent analgesic. Ketamine acts as a non-competitive, non-opiate, N-methyl-D-aspartate (NMDA) receptor antagonist. IDDS has developed a proprietary formulation of ketamine for intranasal administration. Results from five company-sponsored phase I and II clinical trials established that intranasal ketamine provides rapid onset of pain relief with dose-related effectiveness and duration of effect without producing sedation or significant neurological or cardiovascular side effects associated with anesthetic doses. The objectives of this proposal are to demonstrate the safety and analgesic efficacy of the IDDS proprietary formulation of intranasal ketamine for the management of chronic malignant breakthrough pain. Specifically, the project aims to: 1) establish the safety and efficacy of ketamine hydrochloride for the management of moderate-to-severe pain; 2) evaluate the safety and efficacy of transnasal ketamine in a pivotal phase III multi-center, randomized, double-blind, placebo-controlled clinical trail in patients suffering from moderate to severe malignant breakthrough pain; and 3) use the results of the safety and efficacy analyses of the proposed pivotal phase III trial to support the filing of a New Drug Application (NDA) for transnasal ketamine with the U.S. FDA. Dr. Carr, the principal investigator, is an experienced researcher and has successfully conducted the pilot study upon which the present proposal is based.