A Phase IIa placebo-controlled clinical trial of TOPOFEN, a topical anti-migraine therapy for moderate and severe migraine sufferers, showed that the application of a well-known non-steroidal anti-inflammatory drug (NSAID), using the company's proprietary formulation on the skin, over the trigeminal nerve branches, can be a safe and effective alternative treatment for patients suffering from acute migraine.
TOPOFEN, also known as ELS-M11, is a proprietary gel formulation consisting of 5 percent ketoprofen, a potent NSAID. The gel formulation was developed to permeate human skin rapidly and efficiently. Indications that TOPOFEN is currently being evaluated for include acute and chronic migraine, peripheral joint pain, sprains and strains, temporomandibular joint disease, and post-surgical inflammatory pain.
NSAIDs are a widely used class of drugs that relieve pain, reduce fever and stem inflammation. They include aspirin, ibuprofen, naproxen and others. Topical NSAIDs represent an alternative to the oral form of the drugs, which have known safety issues and side effects such as gastrointestinal irritation, bleeding and ulcers, especially when used in higher doses that are often required to relieve migraine pain.
The randomized, crossover, double-blind, placebo-controlled study involved 48 screened adults with a history of episodic migraine with and without aura (the warning signs that can precede headache pain in about 20 percent of sufferers). Patients were instructed to treat five moderate to severe migraines by applying the TOPOFEN gel on the skin, over the three branches of the trigeminal nerve, and to record their symptoms on an electronic diary.
Compared with placebo, TOPOFEN resulted in greater improvement in pain assessments after study drug application, a faster time to pain response, a reduction of migraine-associated symptoms such as nausea, light and sound hypersensitivity, and greater suppression of pain over the 24-hour period that patients were asked to follow each migraine once they applied the gel.
Of the severe migraine patients, 77 percent experienced relief of pain and migraine-associated symptoms and 45 percent had sustained pain relief from two to 24 hours compared to 15 percent of placebo. Also 50 percent of patients who treated their severe pain with TOPOFEN were pain free at 24 hours compared to 25 percent of placebo-treated patients. Patients whose severe headaches were treated with TOPOFEN were at least three times as likely to experience complete relief of associated symptoms (nausea and photophobia) versus placebo. Some patients experienced application-site irritation, predominantly mild or moderate. That was the only reported side effect, which resolved quickly.
Wolfgang Liedtke, M.D., Ph.D., from Duke University will present the results as a member of the team that conducted the research and a paid advisor to Achelios. Liedtke, an associate professor of neurology and attending physician in the Duke Pain Medicine clinics, said, "The results of the study are encouraging, and those of us who treat migraine think it may lead to a meaningful alternative treatment for a substantial number of migraineurs. This study showed that it may be possible to affect severe migraine, which can be a debilitating neurological pain condition, with a topical application to facial trigeminal nerve endings, which was unexpected."
The results of the clinical trial will be presented at the Emerging Science session of the American Academy of Neurology annual meeting in Washington, D.C., on Wednesday, April 22. The study was conducted by scientists from Achelios and the Michigan Headache & Neurological Institute in Ann Arbor, Mich.