BACKGROUND AND OBJECTIVES:Breakthrough cancer pain (BTcP) represents an important clinical challenge in the care of patients with cancer. This trial evaluated the efficacy and long-term tolerability of a sublingual formulation of the fast-acting opioid fentanyl, for the treatment of BTcP in opioid-tolerant patients with cancer. RESEARCH DESIGN AND METHODS: This was a randomized, placebo-controlled, multi-center, phase III trial, conducted in opioid-tolerant male and female patients (aged > or =17 years) with BTcP. The study was conducted at 36 centers across the USA. The study comprised a 2-week open-label titration phase, followed by a double-blind efficacy phase, during which patients received sublingual fentanyl citrate orally disintegrating tablet (sublingual fentanyl ODT) or placebo, in a random order. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. Following efficacy evaluation, patients entered a long-term safety phase of up to 12 months. Adverse events were recorded throughout the study. [ CLINICAL TRIAL REGISTRATION: NCT00262678] RESULTS: A total of 131 patients entered the titration phase, of whom 61 were included in the primary efficacy analysis. Sublingual fentanyl ODT provided significant improvements in SPID relative to placebo at 30 min (49.5 vs. 36.6, p = 0.0004) and 60 min post-administration (143.0 vs. 104.5, p = 0.0002). Furthermore, sublingual fentanyl ODT provided significant improvements in PID and PR compared to placebo, from 10 min post-dose (p = 0.0055 and p = 0.049 for PID and PR, respectively). Patient recruitment was stopped early, due to positive interim analysis results (significant at prespecified level, p < or = 0.0414). Overall, sublingual fentanyl ODT was well-tolerated both systemically and sublingually, with 41 patients experiencing > or =1 study drug-related adverse event (AE). The most common AEs included nausea (12.2%), vomiting (5.3%) and somnolence (4.6%). One serious AE (mild affect lability) was considered possibly related to study medication. The observed pattern of AEs was consistent with that previously observed with fentanyl. CONCLUSIONS:Sublingual fentanyl ODT was efficacious and well-tolerated for the treatment of BTcP in opioid-tolerant patients with cancer. Sublingual fentanyl ODT provided significant improvements in pain intensity compared to placebo, from 10 min post-administration and throughout the 60-min post-dose assessment period. Sublingual fentanyl ODT was well tolerated over 12 months of treatment.
RCT Entities:
BACKGROUND AND OBJECTIVES:Breakthrough cancer pain (BTcP) represents an important clinical challenge in the care of patients with cancer. This trial evaluated the efficacy and long-term tolerability of a sublingual formulation of the fast-acting opioid fentanyl, for the treatment of BTcP in opioid-tolerant patients with cancer. RESEARCH DESIGN AND METHODS: This was a randomized, placebo-controlled, multi-center, phase III trial, conducted in opioid-tolerant male and female patients (aged > or =17 years) with BTcP. The study was conducted at 36 centers across the USA. The study comprised a 2-week open-label titration phase, followed by a double-blind efficacy phase, during which patients received sublingual fentanyl citrate orally disintegrating tablet (sublingual fentanyl ODT) or placebo, in a random order. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. Following efficacy evaluation, patients entered a long-term safety phase of up to 12 months. Adverse events were recorded throughout the study. [ CLINICAL TRIAL REGISTRATION: NCT00262678] RESULTS: A total of 131 patients entered the titration phase, of whom 61 were included in the primary efficacy analysis. Sublingual fentanyl ODT provided significant improvements in SPID relative to placebo at 30 min (49.5 vs. 36.6, p = 0.0004) and 60 min post-administration (143.0 vs. 104.5, p = 0.0002). Furthermore, sublingual fentanyl ODT provided significant improvements in PID and PR compared to placebo, from 10 min post-dose (p = 0.0055 and p = 0.049 for PID and PR, respectively). Patient recruitment was stopped early, due to positive interim analysis results (significant at prespecified level, p < or = 0.0414). Overall, sublingual fentanyl ODT was well-tolerated both systemically and sublingually, with 41 patients experiencing > or =1 study drug-related adverse event (AE). The most common AEs included nausea (12.2%), vomiting (5.3%) and somnolence (4.6%). One serious AE (mild affect lability) was considered possibly related to study medication. The observed pattern of AEs was consistent with that previously observed with fentanyl. CONCLUSIONS: Sublingual fentanyl ODT was efficacious and well-tolerated for the treatment of BTcP in opioid-tolerant patients with cancer. Sublingual fentanyl ODT provided significant improvements in pain intensity compared to placebo, from 10 min post-administration and throughout the 60-min post-dose assessment period. Sublingual fentanyl ODT was well tolerated over 12 months of treatment.