42264
document
Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain . 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 .
42265
Intervention_Pharmacological
sublingual fentanyl orally disintegrating tablet
42266
Intervention_Pharmacological
fast-acting opioid fentanyl
42267
Intervention_Pharmacological
sublingual fentanyl citrate orally disintegrating tablet ( sublingual fentanyl ODT )
42268
Intervention_Control
placebo
42269
Intervention_Pharmacological
fentanyl ODT
42270
Outcome_Pain
sum of pain intensity difference ( SPID )
42271
Outcome_Physical
over 30 min post-administration
42272
Outcome_Pain
pain intensity difference ( PID )
42273
Outcome_Pain
pain relief ( PR )
42274
Outcome_Other
long-term safety phase of up to 12 months
42275
Outcome_Adverse-effects
Adverse events
42276
Outcome_Pain
SPID
42277
Outcome_Pain
PID
42278
Outcome_Pain
PR
42279
Outcome_Other
well-tolerated both systemically and sublingually
42280
Outcome_Adverse-effects
drug-related adverse event
42281
Outcome_Adverse-effects
nausea
42282
Outcome_Adverse-effects
vomiting
42283
Outcome_Adverse-effects
somnolence
42284
Outcome_Adverse-effects
serious AE ( mild affect lability )
42285
Participant_Condition
cancer
42286
Participant_Condition
opioid-tolerant
42287
Participant_Sex
male and female
42288
Participant_Age
aged > or =17 years
42289
Participant_Sample-size
131
42290
Participant_Sample-size
61