Absorption and tolerability of BEMA (BioErodible MucoAdhesive) fentanyl in cancer subjects with grade 1 mucositis

Abstract

20559 Background: Oral transmucosal delivery of fentanyl is a rapid and proven route of administration for the management of breakthrough pain in cancer patients. 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 membranes. In subjects with normal intact oral mucosa, fentanyl is rapidly absorbed from BEMA fentanyl. This study was designed to determine if the absorption of fentanyl is more rapid or extensive in the presence of grade 1 mucositis and if the disc causes irritation to the mucosa membrane. Methods: Seven cancer subjects with grade 1 mucositis and seven age- and gender-matched control cancer subjects without mucositis received a single open-label dose of BEMA fentanyl 200 μg applied to the buccal mucosa. Serial blood samples for analysis of fentanyl plasma concentrations were collected immediately prior to application of BEMA fentanyl and for 4 hours post-dosing. All subjects were monitored for safety throughout the study and were serially questioned regarding irritation at the application site. Results: Overall fentanyl exposure following the 200 μg BEMA fentanyl dose was not higher in subjects with mucositis than those without, as assessed by the mean 4-hour AUC (1.14 vs. 1.29 hr*ng/mL, respectively) and mean Cmax values (0.47 vs. 0.69 ng/mL, respectively). All seven subjects with mucositis became mucositis pain-free at one or more time points following BEMA fentanyl application. The only observed adverse event was mild somnolence reported by two subjects with mucositis. There was no evidence of respiratory depression or significant changes in blood pressure. Conclusions: Application of BEMA fentanyl to an area of grade 1 mucositis does not expose cancer patients to a risk of increased fentanyl plasma concentrations compared to cancer patients without mucositis. BEMA fentanyl is well tolerated at a 200 μg dose in subjects with and without mucositis and does not cause local irritation on application to an area of grade 1 mucositis. 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