? Ethanol solution administered intralesionally in patients with CVM is considered the most effective medical treatment but frequently results in complications related to its high systemic absorption and local extravasation. This Phase 2 study proposes to compare the systemic absorption of ethanol solution with a less diffusible ethanol gel in CVM patients. The secondary study objectives are to compare the systemic and local safety, and the pharmacodynamic and efficacy profiles. Comparison of these endpoints has been requested by regulatory authorities. ? ? The Phase 2 study will be followed by a Phase 3 comparative study (gel vs. solution) in a larger sample size and a submission for a new drug application (NDA) in CVM. The Phase 2 study will be a randomized, open-label, comparative, single-center study and will include a total of 24 patients (12 patients per treatment group) with clinically and radiologically diagnosed CVM who will receive a single infusion of one of the two test formulations under general anesthesia. After product infusion, plasma monitoring of ethanol will be performed in order to assess the pharmacokinetic parameters of the two products (Cmax, Tmax, AUC, percent of ethanol absorption). The other assessment parameters will include systemic safety outcomes (cardio-pulmonary, metabolic, hematological) during the infusion procedure, local safety outcomes during a 4-month study follow-up, embolosclerosing activity (lesional size reduction measurement by magnetic resonance imaging) and clinical efficacy (self-evaluation of pain, swelling, functional signs and esthetic damage of the test lesion by the patients before and after treatment). The local reactions of the test lesion to treatment (occurrence of thrombi, swelling and granuloma) will also be assessed and the adverse events will be reported during the study period. ? ? The relevance of this proposed study is that patients with CVM (which causes pain, swelling, disfigurement and is sometimes life-threatening) may benefit from a new product that is improved in terms of safety compared to the current treatment used in clinical practice. Moreover, if this product becomes available, it will be the first for this indication in the US and will fill an unmet medical need. ? ? ?
