A dose titration study of fentanyl buccal soluble film for breakthrough cancer pain in Taiwan.

Fentanyl buccal soluble film (FBSF), a new formulation of fentanyl, is developed for the treatment of breakthrough pain (BTP) in opioid-tolerant patients with cancer. This study aimed to assess the feasible dose range of FBSF required for Taiwanese population. This was an open-label, multicenter, noncomparative study. Cancer patients who were aged 20 years or older and had a stable regimen equivalent to 60 to 1000 mg/day of oral morphine, 20 to 120 mg/day of intravenous morphine, or 25 to 300 μg/h of transdermal fentanyl for at least 1 week were enrolled. The primary endpoint was the feasible dose range of FBSF. Secondary endpoints included difference in pain intensity at 30 minutes (PID30), percentage of episodes requiring rescue medication, and overall satisfaction. Adverse events (AEs) and serious AEs (SAEs) were recorded for safety measurements. The final effective dose in the per-protocol (PP) population (n = 30) ranged from 200 to 800 μg, of which 26 subjects (86.7%) achieved an effective dose range of 200 to 400 μg. Among the 283 BTP episodes recorded in the maintenance period, the mean PID30 was 4.0, and only 13 events (4.6%) required rescue medication. For 63.6% of the BTP episodes, patients rated their satisfaction as good to excellent. Only 5% of AEs were considered drug-related. Individualized dose titration is recommended for BTP management for patients' benefit. Overall, FBSF was effective and well tolerated and was positively correlated with patients' background opioid dose for persistent pain management.

Chiou TJ ，Chao TC ，Chao TY ，Huang JS ，Chang YF ，Wang CH ... -  《Cancer Reports》

Proportional dose of rapid-onset opioid in breakthrough cancer pain management: An open-label, multicenter study.

Yen TY ，Chiou JF ，Chiang WY ，Su WH ，Huang MY ，Hu MH ，Wu SC ，Lai YL ... -  《-》

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

Chiang YH ，Lien CT ，Su WH ，Yen TY ，Chen YJ ，Lai YL ，Lim KH ，Dai KY ，Chung HP ，Hung CY ，Leu YS ... -  《BMC Palliative Care》

A randomized, placebo-controlled study of a new sublingual formulation of fentanyl citrate (fentanyl ethypharm) for breakthrough pain in opioid-treated patients with cancer.

Oromucosal fentanyl is currently used for the treatment of breakthrough pain (BTP) in opioid-treated cancer patients. Ethypharm developed a sublingual formulation of fentanyl suprabioavailable to oral transmucosal fentanyl citrate with a higher early systemic exposure and a shorter Tmax. This study evaluated the efficacy and safety profile of fentanyl Ethypharm (FE) in relieving BTP in opioid-treated cancer patients. Opioid-treated adult cancer patients, experiencing 1 to 4 episodes of BTP per day, were included in the study. After an open-label titration period to identify an optimal dose that would provide adequate pain relief for 2 consecutive episodes of BTP with an acceptable level of adverse events, patients were randomly assigned to a double-blind, placebo-controlled, crossover period with 1 of 13 prespecified sequences of 9 tablets (6 tablets of FE of the dose identified during the open-label titration and 3 placebo). Pain intensity and pain relief were recorded at 3, 6, 10, 15, 30, and 60 minutes after study drug administration. Adverse events were recorded. The primary end point was the sum of pain intensity differences (SPID) at 30 minutes. The distribution of optimal dosages of FE was as follows: 133 µg, 35.9%; 267 µg, 30.8%; 400 µg, 14.1%; 533 µg, 12.8%; and 800 μg, 6.4%. In the modified intention-to-treat population (n = 73), FE significantly improved mean (SE) SPID compared with placebo at 30 minutes (75.0 [49.8] vs 52.5 [52.8]; P < 0.0001). FE significantly improved SPID, pain intensity difference, and pain relief compared with placebo from 6 to 60 minutes' postadministration. Patients with BTP who received placebo required the use of rescue medication more often than those treated with FE (38.4% vs 17.5%; P < 0.0001). A significant improvement in pain scores (>33% and >50% reductions) was also reported for BTP treated with FE. Pain scores for patients with BTP with a neuropathic component (13 patients) were lower with FE than for those receiving placebo, but the difference was not significant. AEs were of mild or moderate severity and typical of opioid drugs. This newly developed galenic formulation with a higher early systemic exposure and a shorter Tmax compared with oral transmucosal fentanyl citrate makes FE a particularly suitable formulation for the management of BTP in opioid-treated cancer patients due to the very rapid onset of action. FE provided significant improvement in pain intensity of BTP compared with placebo as early as 6 minutes' postadministration with a sustained effect over 60 minutes. FE was well tolerated by patients. ClinicalTrials.gov identifier: NCT 01842893.

Novotna S ，Valentova K ，Fricova J ，Richterova E ，Harabisova S ，Bullier F ，Trinquet F ，ETHYFYL Study Group ... -  《-》

Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study.

Simpson DM ，Messina J ，Xie F ，Hale M ... -  《CLINICAL THERAPEUTICS》