Adverse events affecting the mouth in two clinical trials of BEMA (BioErodible MucoAdhesive) Fentanyl

Abstract

20648 Background: The BEMA drug delivery system was designed for rapid oral transmucosal drug delivery with dose to dose reliability of plasma concentrations and ease of patient use. BEMA Fentanyl consists of a small, dissolvable, polymer disc formulated with the opioid narcotic fentanyl for application to the buccal (inner lining of cheek) membranes. The mucoadhesive polymers adhere and rapidly deliver fentanyl across the capillary-rich mucosa. Methods: Subjects with cancer-related breakthrough pain who were receiving concomitant chronic opioid therapy were enrolled in two studies: a double-blind, randomized, placebo-controlled, multiple crossover study (FEN-201) and an open-label study (FEN-202). In FEN-201, subjects entered a titration period followed by a double-blind period during which they received 6 doses of BEMA Fentanyl and 3 doses of placebo in random sequence. In FEN-202, subjects successfully completing FEN-201 and a second group of subjects meeting the same entry criteria as for FEN-201 were enrolled. Subjects in both studies were titrated to an effective dose (starting at 200 μg) and then continued with dosage adjustment as required. Results: In FEN-201, 5 of 151 subjects (3.3%) reported oral mucosa-associated adverse events (AEs), including 2 subjects with mucosal inflammation (mucositis) and 3 subjects with oral candidiasis (thrush). None of these events were considered to be related to BEMA Fentanyl, and none were severe in intensity. In FEN-202, adverse oral symptoms were seen in 11 of 220 subjects (5.0%). In 4 subjects, the symptoms were considered to be related to local cancer or infection. In the 7 remaining subjects, the oral events were considered to be potentially attributable to BEMA Fentanyl (3.2%). The events were mild in 6 subjects and moderate in 1 subject. None of the subjects discontinued use of BEMA Fentanyl in either FEN-201 or FEN-202 as a result of BEMA Fentanyl related adverse oral symptoms. Conclusions: In these studies, BEMA Fentanyl exhibited an excellent safety profile with respect to oral AEs, which is of particular importance in a population of cancer patients. Each of the events is typical of the background condition and treatments of the study population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration BioDelivery Sciences International BioDelivery Sciences International BioDelivery Sciences International BioDelivery Sciences International