Trial Information

Procedural Pain Treatment With Transmucosal Sublingual Fentanyl Tablet in Colonoscopy Patients

The purpose of this study is to evaluate the efficacy of fentanyl transmucosal tablet to
placebo in patients having colonoscopy.

Fentanyl is a highly lipophilic drug absorbed very rapidly through the oral mucosa and more
slowly through the gastrointestinal tract. Orally administered fentanyl undergoes pronounced
hepatic and intestinal first pass effects.

Abstral® is a quick dissolving sublingual tablet formulation. Rapid absorption of fentanyl
occurs over about 30 minutes following administration of Abstral®. The bioavailability of
Abstral® has not been studied but is estimated to be about 70%. Mean maximal plasma
concentrations of fentanyl range from 0.2 to 1.3 ng/ml (after administration of 100 to 800
µg Abstral®) and are reached within 22.5 to 240 minutes.

Fentanyl is metabolised primarily via CYP3A4 to a number of pharmacologically inactive
metabolites, including norfentanyl. Within 72 hours of intravenous fentanyl administration
around 75% of the dose is excreted into the urine, mostly as metabolites, with less than 10%
as unchanged drug. About 9% of the dose is recovered in the faeces, primarily as
metabolites. Total plasma clearance of fentanyl is about 0.5 l/h/kg. After Abstral®
administration, the main elimination half-life of fentanyl is about 7 hours (range 3-12.5
hours) and the terminal half-life is about 20 hours (range 11.5-25 hours). Impaired hepatic
or renal function could cause increased serum concentrations. Elderly, cachectic or
generally impaired patients may have a lower fentanyl clearance, which could cause a longer
terminal half-life for the compound.

This is a randomized controlled double-blind study. A total of 200 patients will be
included. The patients are recruited from 18-85 year old male or female patients undergoing
colonoscopy. In view of previous studies (Amer-Cuenca et al. 2011) it can be calculated that
87 patients will be needed per group to demonstrate a 30% decrease in the worst experienced
pain at a level of significance P = 0.05 and power of 90%. Because of possible dropouts, 100
patients will be recruited to both groups. Pain will be assessed by numeral rating scale
(NRS). For the calculation of the sample size, coefficient of variation is assumed to be 70%
in both groups.