Medications In The Pipeline: Intranasal Fentanyl Spray Versus Oral Transmucosal Fentanyl Citrate

A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial

Current Medical Research and Opinion, 10/08/09

“Mercadante S et al. – In this open–label, randomised, crossover trial, significantly more patients attained faster ‘meaningful’ pain relief with intranasal fentanyl spray (INFS) than oral transmucosal fentanyl citrate (OTFC), and more patients preferred INFS to OTFC.”

Results:

Among the intention-to-treat population (n ¼ 139):
• median time to onset of ‘meaningful’ pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to ‘meaningful’ pain-relief onset with INFS ( p50.001). PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing.
• Significantly more INFS-treated breakthrough pain episodes achieved clinically important pain relief (_33% and _50% PI reduction) up to 30 minutes post-dosing.
• The proportions of episodes treated with INFS and OTFC achieving a PI reduction of _33% at 5 minutes were 25.3% versus 6.8% ( p50.001), and at 10 minutes were 51.0% versus 23.6% ( p50.001), respectively
• The proportions of episodes treated with INFS and OTFC achieving a _50% PI reduction at 5 minutes were 12.8% versus 2.1% ( p50.001), and at 10 minutes were 36.9% versus 9.7% ( p50.001), respectively.
• Both treatments were well tolerated. In the safety population (n ¼ 139), 56.8% (n ¼ 79) of patients experienced _1 AE during the trial. The only AE that occurred in _5% of patients in either treatment group was nausea. Among those patients who experienced serious AEs (13.7%, n ¼ 19), none were considered to be related to either study medication.
• There was a weak correlation between effective INFS doses and background opioid doses.

Treatment administration:
• Up to four episodes of BTP per day were treated with study medication, intranasal fentanyl spray (INFS), as described below.
• Intranasal fentanyl spray has recently received marketing authorization from the Committee for Medicinal Products for Human Use and will be launched under the trade name Instanyl (Nycomed, Denmark).
• Doses of 50, 100 and 200 mg fentanyl (using INFS solutions of 0.5 mg/ml, 1.0 mg/ml and 2.0 mg/ml, respectively) were taken as a single dose in one nostril. A second INFS dose was permitted 10 minutes after the first, if required, taken in the other nostril. Rescue analgesics were permitted 10 minutes after the second INFS administration if pain relief was still insufficient.
• The comparator medication, oral transmucosal fentanyl citrate (OTFC) (Actiq, Cephalon, USA), was used at six doses: 200, 400, 600, 800, 1200 or 1600 mg in the form of single compressed lozenges with integral oromucosal applicators. One lozenge equalled one dose. OTFC was administered according to manufacturer’s recommendations (15 minutes in the oral cavity between cheek and gum). A second OTFC dose was permitted 30 minutes after the first, if required. Rescue analgesics were allowed, as needed, 45 minutes (if a second OTFC dose was not taken) or 60 minutes (if a second OTFC dose was taken) after start of administration.