Ketoprofen 10% cream (Ketotransdel) is currently undergoing phase III clinical trials as a topical therapy to reduce pain associated with soft tissue injuries.10 In a placebo-controlled study, time to onset of pain relief was about 40 minutes faster and time to end of analgesic effect was about 45 minutes longer with topical ketoprofen 10% compared with the effects of placebo.
Drug Development Setbacks
JZP-6 (Zyrem, sodium oxybate) was evaluated by the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee for the treatment of fibromyalgia.19,20 The committees voted 20 to 2 that the benefit-risk ratio did not support approving sodium oxybate. There was a concern for abuse of the agent and accidental overdose, even with the proposed REMS. The committees did, however, suggest that the company perform additional safety and effectiveness trials. The committees also recommended that the developer compare sodium oxybate to other agents that are currently used to treat fibromyalgia. Sodium oxybate is currently FDA approved to treat narcolepsy and is a schedule III controlled substance.
Naproxcinod, which was being developed for relieving the signs and symptoms of osteoarthritis, received a complete response letter for their New Drug Application on July 22, 2010.21 The FDA informed NicOx that it did not approve the application. Naproxcinod was to be a first-in-class cyclooxygenase-inhibiting nitric oxide-donating antiinflammatory. The FDA recommended that NicOx perform one or more long-term controlled studies in order to assess the cardiovascular and gastrointestinal safety of naproxcinod. NicOx still plans on discussing next steps with the FDA and continuing the European regulatory process for this agent.22 It is currently under review by the European Medicines Agency; the Marketing Authorization Application was filed in December 2009. NicOx has also announced that they will be closing their US-based headquarters.
Methylnaltrexone tablets (Relistor) are currently undergoing phase III clinical trials for the treatment of chronic nonmalignant pain in patients who experience opioid-induced constipation (OIC).11 The phase III program will be international in scope and plans to enroll about 700 patients with OIC in a double-blind, placebo-controlled manner. The primary study endpoint will be the proportion of patients with a rescue-free bowel movement within four hours of receiving methylnaltrexone during an initial four-week double-blinded period. Currently methylnaltrexone is FDA approved as a subcutaneous injection for the treatment of OIC in patients with advanced illness who are receiving palliative care when they have not responded to laxative therapy. Treatment beyond four months has not been evaluated. Patients with known or suspected bowel obstruction should not use methylnaltrexone. The most common side effects in clinical trials were abdominal pain, flatulence, nausea, dizziness, diarrhea, and hyperhidrosis. Subcutaneous methylnaltrexone is also approved for use in the European Union, Canada, Australia, and Brazil.