Ivermectin Cream (CD5024)
An agent currently under investigation is CD5024 1% cream, which is a new topical formulation of the acaricidal compound, ivermectin. Although the exact pathophysiology is yet to be elucidated, one well-known hypothesis for the etiology of rosacea is the presence of Demodex mites in the pilosebaceous unit of affected individuals. Reports have been published on cutaneous demodicidosis responding to oral ivermectin and topical permethrin, but data is lacking on the topical application of ivermectin alone.
There are currently three Phase III studies ongoing, one comparing CD5024 1% cream to metronidazole cream 0.75% (ClinicalTrials.gov identifier NCT01493947) and two similar studies comparing CD5024 1% cream to azelaic acid 15% gel with an initial randomized controlled phase for 12 weeks, and a comparator extension phase for 40 weeks (ClinicalTrial.gov identifiers NCT01494467 and NCT01493687). The projected trial completion date is August 2013.
Adrenergic Receptor Antagonists: Brimonidine and Oxymetazoline
Novel therapies to treat the erythema associated with rosacea are under development and have the potential to fill a void in the arsenal of rosacea therapeutics. The adrenergic receptor antagonists brimonidine tartrate and oxymetazoline, which have potent vasoconstrictive activity and anti-redness capabilities, are currently found in eye drops for glaucoma and a nasal decongestant spray, respectively.
Brimonidine tartrate, an alpha-2 agonist also known as CD07805/47, has been shown in a two part dose-finding Phase II study to be safe and efficacious in reducing the erythema of rosacea. A single application of the 0.5% gel reduced erythema between 30 minutes to 12 hours, as measured with an objective chromameter. In part B of the study, two dosages (0.18% and 0.5%) of the gel was compared to vehicle over a 4 week period in 269 subjects. No tachyphylaxis, aggravation of symptoms or rebound erythema was observed. The majority of adverse effects were skin-related and mild and transient in nature. The 0.5% gel once daily was significantly more effective according to both patient and clinician assessments (≥ two-grade improvement) and is the dose that has gone forward in Phase III clinical development to confirm safety and efficacy. Results of the Phase III randomized controlled trials are anticipated to be released in the fourth quarter of 2012.
Oxymetazoline or AGN-199201, a potent alpha-1 and partial alpha-2 receptor agonist, has been shown in case reports to be an effective agent for reducing facial erythema. It has been formulated into a cream and is currently in clinical development for the treatment of erythematotelangiectatic rosacea (ClinicalTrials.gov identifier NCT 01579084).