Lack of adverse events affecting the mouth in three clinical trials of BEMATM (BioErodible MucoAdhesive) Fentanyl

The BEMA^TM drug delivery system was designed to improve oral transmucosal dosing reliability, tolerability, and patient acceptance. BEMA^TM Fentanyl is a bilayer polymer drug delivery system with a mucoadhesive layer that delivers fentanyl across the capillary rich buccal mucosa. The entire dosage form dissolves within 15-30 minutes of application.

Safety data were combined from three BEMA^TM Fentanyl clinical trials (a trial in cancer patients with and without mucositis, a double-blind crossover study of efficacy in cancer patients with breakthrough pain, and a long-term safety study). Over 60,000 doses of BEMA^TM Fentanyl were used by 301 subjects. Relevant events for inclusion in this analysis were identified by searching adverse event listings for any terms including “oral,” “ging*,” “mouth,” “stoma*,” “tooth,” “dental*” and “mucos*” (where * represents any following text), and additionally by manual search. “Dry mouth,” “candidiasis” and events which are clearly related to local recurrence of cancer, infection (e.g., Herpes Zoster), or complications of cancer treatment were excluded. Overall, treatment with BEMA^TM Fentanyl was associated with a low incidence (4.6%) of application site reactions. Considering Investigator attribution of causality, only 1.3% of subjects had events which were considered to be related or possibly related to study drug. Stomatitis was seen in 5 subjects (1.6%); all events of stomatitis were mild in severity, and none led to BEMA^TM Fentanyl discontinuation. No other individual event occurred at an incidence of ³1%. There were no oral serious adverse events related to study drug administration, and only one severe reaction (odynophagia) occurred; the event resolved after 4 days without adjustment to study drug administration. In this combined analysis of three studies, BEMA^TM Fentanyl exhibited an excellent safety profile with respect to oral adverse events, which is of particular importance in a population of cancer patients.

Research supported by BioDelivery Sciences International