Washington - Results of a phase 3a laboratory study suggest that a novel topical nitroglycerin (NTG) gel (Vascana, MediQuest Therapeutics) has exciting potential as a safe and effective treatment alternative for patients with Raynaud's phenomenon, said Laura K. Hummers, M.D., at the annual meeting of the American College of Rheumatology here.
Dr. Hummers is assistant professor of medicine and co-director of the scleroderma center, Johns Hopkins University, Baltimore.
The study enrolled 37 patients with primary or secondary Raynaud's phenomenon who had discontinued any existing vasodilator therapy for at least two weeks. In random fashion, they applied placebo or the NTG gel (0.5 percent or 1.25 percent) to the fingers and underwent five minutes of exposure in a cold chamber maintained at -20 degrees C. Each study agent was applied in two separate sessions.
The primary outcome measure was blood flow recovery, which was assessed based on laser Doppler measurements collected prior to gel application and at prespecified times beginning five minutes after cold chamber exposure and continuing through 120 minutes. Blood flow was significantly reduced after cold exposure, but comparisons between both NTG preparations and placebo showed statistically significant differences favoring the active treatments for enhancing recovery.
Blood flow returned to the baseline level approximately 30 minutes faster when either NTG gel was applied prior to cold exposure compared with placebo. In addition, significantly higher proportions of patients achieved return to baseline blood flow levels during the follow-up period after application of the NTG 0.5 and 1.25 percent gels compared with placebo, 65.7 percent and 67.6 percent, respectively, vs. 46.5 percent.
The NTG treatments were well tolerated. Recorded adverse events consisted of headache, lightheadedness and skin irritation. However, those events occurred in all treatment groups and each involved only one or two patients in total. There were no serious adverse events or significant decreases in blood pressure as can occur after application of commercially available topical NTG products.
"This topical NTG gel is showing great promise for addressing an unmet need in the treatment of primary and secondary Raynaud's," Dr. Hummers says. "It could be a welcome option for the many symptomatic patients who are unable to tolerate oral vasodilator therapy, as well as a potentially useful adjunct to that systemic treatment. In addition, it could provide a convenient modality for as-needed use in the large group of individuals with primary Raynaud's who are mildly symptomatic."
"Raynaud's is a common and debilitating condition for which available nonpharmacological management recommendations and off-label pharmacological treatment options are less than satisfactory," said Frederick J. Dechow, Ph.D., president and CEO, MediQuest Therapeutics, Bothell, Wash. "This topical NTG gel was developed specifically to address the vasospasm that leads to symptom development, but to provide a localized pharmacologic effect without causing significant adverse effects that can develop from systemic absorption. The results seen to date in clinical studies suggest we are achieving those goals."
The NTG gel formulation is based on a drug delivery system (Topical Amphi-Matrix) in which organic and water phases are present in equal proportions and held together with a unique proprietary emulsion system that maintains product stability. The topical product is pharmaceutically elegant - it is nongreasy, nonirritating and disappears from the skin's surface within a few minutes after application so that it delivers the active ingredient for a short period of time that is adequate to produce the desired vasodilatory response without leading to significant systemic absorption.
"Within five minutes of application to the fingers, blood flow increases by between 100 and 300 percent, but the material is rapidly metabolized, so there is no enduring source of drug that can lead to systemic side effects," Dr. Dechow explains.
An ambulatory, placebo-controlled, in-life study has been completed, and a second phase 3 ambulatory study will be under way. Symptom prevention and relief are the primary endpoints in those trials.