Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated patients with chronic low back pain: a randomized, placebo-controlled study

Background: Short-acting opioids are commonly used to treat breakthrough pain ( BTP) and rapid-onset formulations are being developed to improve the effectiveness of this approach. Fentanyl buccal tablet ( FBT) is a new formulation of fentanyl that enhances transbuccal drug delivery via an effervescent reaction and may provide relatively rapid-onset analgesia. FBT was evaluated for BTP in opioid-treated patients with chronic low back pain - the first such study in a population with chronic non-cancer pain. Design: Randomized, double-blind, placebo-controlled. Patients and setting: Patients with chronic low back pain receiving long-term opioid therapy at 16 pain treatment centers in the United States. Procedures: Following open-label titration to identify an effective FBT dose, patients were randomly assigned to one of three double-blind dose sequences ( six doses of FBT, three placebo) to treat nine BTP episodes. Pain intensity ( PI), measured on an 11-point scale ( 0 = no pain; 10 = worst pain), and other outcomes were assessed for 2 h after dosing. Data analysis: The primary efficacy measure was the sum of pain intensity differences ( PIDs) for the first 60 min ( SPID60); secondary efficacy measures included PIDs at other time points, pain relief ( PR), meaningful PR, time to meaningful PR, use of supplementary BTP medication, and self/investigator-reported adverse events. Results: Of the 124 patients screened, 10 patients were enrolled, 84 identified an effective FBT dose, and 77 entered the double-blind phase. SPID60 significantly favored FBT ( p < 0.0001). All secondary measures also favored FBT, with PIDs and PR showing significant differences versus placebo as early as 10 and 1 min, respectively. An improvement in PI score of >= 33% occurred in a significantly larger proportion of FBT-treated episodes versus placebo from 1 min ( 20% vs. 11%, p < 0.01) through 2 h ( 65% vs. 28%, p < 0.0001). Patients were approximately four times more likely to require supplemental opioids for BTP episodes following administration of placebo compared with episodes treated with FBT. AEs were typical for opioids, and were mostly reported during dose titration. Limitations of this study may be related to its open-label dose-titration phase ( which has the potential to compromise blinding) and the recruitment of patients from pain clinics, which could potentially yield a study population that is not representative of the general population with BTP. Conclusions: FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain.