Pain Drugs: A Diverse Field

Phase III

• Transdel Pharmaceuticals announced positive Phase III data for Ketotransdel® (TDLP-110), a transdermal non-steroidal anti-inflammatory drug. The Phase III study of the cream showed statistically greater reductions in pain for acute soft tissue injuries. http://clinicaltrials.gov identifier: NCT00765700.

• Interim analysis for MoxDuo IR in a pivotal Phase III shows the sample size of 140 patients is statistically powerful and does not require further enrollments. This comparative study is being conducted in 10 US-based centers, evaluating analgesic efficacy and tolerability of a flexible dose regimen (12 mg/8 mg) versus a fixed low dose (3 mg/2 mg) of MoxDuo IR in patients with moderate to severe pain following total knee replacement surgery. http://clinicaltrials.gov identifier: NCT01055015.

• Cumberland Pharmaceuticals published new data supporting the safety and efficacy of Caldolor® (ibuprofen) Injection in pre- and post-operative orthopedic surgery patients. The study concluded that IV ibuprofen significantly decreased pain and morphine use when compared with placebo. This multi-center, randomized, double-blind placebo-controlled trial evaluated 185 adults undergoing orthopedic surgery at eight hospitals. Subjects were randomized to receive either 800 mg IV ibuprofen or placebo every six hours, and pain was measured through patient self-assessment in the immediate post-operative period through hour 28 of the study. All patients had access to intravenous morphine. The study met its primary endpoint; patients who received IV ibuprofen reported a 26 percent reduction in pain with movement. The study met its secondary endpoints, pain assessed during rest was reduced by 32 percent in patients receiving IV ibuprofen. These patients used nearly 31 percent less morphine than those who received placebo. http://clinicaltrials.gov identifier: NCT00470600.

Pain Medications in Development

Submissions

• The FDA's Anesthetic and Life Support Drugs Advisory Committee voted in favor of expanding the pain indications for Eli Lilly's Cymbalta® (duloxetine HCl) to a broader pain population. The committee reviewed efficacy and safety data from three new Cymbalta studies in chronic low back pain and two new studies in chronic pain due to osteoarthritis of the knee, along with overall safety data for the medication. Cymbalta is approved for management of diabetic peripheral neuropathic pain and fibromyalgia in the areas of pain, and is also approved for other indications. In split votes, the advisory committee was supportive of the adequacy of evidence for efficacy in chronic low back pain based on two positive studies, but not chronic pain due to osteoarthritis based on a single positive study. The committee also voted that there was insufficient evidence of significant additional efficacy of 120 mg compared with 60 mg in these conditions. The committee voted positively regarding the overall safety profile of Cymbalta.

• In July, the advisory committees for Anesthetic and Life Support Drugs and Drug Safety and Risk Management voted against the FDA's proposed classwide REMS for extended-release and long-acting opioid analgesics. According to Jill Wechsler's View from Washington column (September 2010, Applied Clinical Trials). "the practitioners and academics on the panels said that FDA's plan was too weak and unlikely to do much to stop unsafe use of potentially dangerous products..."

Editor's Note: Applied Clinical Trials will next report on pain in the August 2011 issue. The new section entitled Therapeutic Corner, will focus on specific clinical trial needs for pain trials. Please send your information, news, or ideas to lhenderson@advanstar.com